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[ { "id": "e06f8299-06eb-49f5-8bfa-b8efbc92c317", "type": "title", "text": [ "Cytotoxicity of Fas ligand against lymphoma cells with radiation-induced Fas antigen." ], "offsets": [ [ 0, 85 ] ] }, { "id": "24ef038b-6c4e-4626-bf48-8862226c6266", "type": "abstract", "text": [ "Fas antigen, also termed APO-1 or CD95, is a transmembrane protein and a member of the tumor necrosis factor receptor/nerve growth factor receptor superfamily which mediates apoptosis upon oligomerization. The Fas/Fas ligand system is considered to be a key regulator of apoptosis. Recently, we have demonstrated that Fas antigen expression is induced by low-dose irradiation of some types of lymphomas, and we also demonstrated that irradiation-induced Fas antigen expression increased with the passage of time until peaking at 48 h after irradiation in CML-C1, CML-C2, DL-40, and DL-95 cell lines. In this study, we also examined the potential cytotoxicity of Fas ligand peptide against several types of lymphoma/leukemia cell lines that showed induction of Fas antigen expression under irradiation. Flow cytometry analysis was performed at 6, 24 and 48 h after irradiation. Samples (1 x10(6) cells/ml) from irradiated and non-irradiated cells of each cell line were incubated with or without 5 microg/ml of Fas ligand peptide for 2 h at 37 degrees C in a humidified atmosphere of 5% carbon dioxide (CO2) in air. The killing effect of Fas ligand against cell lines of CML-C1, DL-40, and DL-95 were clearly identified as the percentage of cells with Fas antigen expression induced by irradiation. Concerning HD-70 cell line, for which soluble Fas antigen has been identified, the killing effects were clearly observed in samples pre-treated with PBS washings. To our knowledge, this is the first report describing a possible application of the Fas/Fas ligand system in treatment of certain types of malignancies in which Fas antigen is inducible by irradiation." ], "offsets": [ [ 86, 1748 ] ] } ]

[ { "id": "e5027718-b119-4714-9e46-d2985d52b367", "type": "Gene", "text": [ "Fas ligand" ], "offsets": [ [ 16, 26 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cf017e31-b421-4685-9b5f-4dadbc8daded", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 73, 84 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "08efd60d-b0ff-4885-87b3-85d1b12e10bc", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 86, 97 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c0d39d7b-392e-454a-bd83-c044dc6ef7f9", "type": "Gene", "text": [ "APO-1" ], "offsets": [ [ 111, 116 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "86ec2fe7-b0cd-43f3-9476-358fed66a2e7", "type": "Gene", "text": [ "CD95" ], "offsets": [ [ 120, 124 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c7cc9dfe-5c56-442a-9771-e97a00f3fb1f", "type": "FamilyName", "text": [ "tumor necrosis factor receptor/nerve growth factor receptor superfamily" ], "offsets": [ [ 173, 244 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e8777aca-ab7a-4fbe-89de-ce79af38d817", "type": "Gene", "text": [ "Fas" ], "offsets": [ [ 296, 299 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "de2a1759-87d6-4ba5-b1f0-6f9b078d883c", "type": "Gene", "text": [ "Fas ligand" ], "offsets": [ [ 300, 310 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ce50f797-5060-45a7-911a-5d5b530532a6", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 404, 415 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "41229a66-dd2f-4349-8fa6-041b1e08ccff", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 540, 551 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0704a00b-0bab-4cb2-92b8-bdc3f78203bd", "type": "Gene", "text": [ "Fas ligand" ], "offsets": [ [ 748, 758 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1a69d207-2bd5-4e7f-9b16-ad48b7e9c99b", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 846, 857 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "95249941-7d75-485c-bfb8-54d3f9524ea3", "type": "Gene", "text": [ "Fas ligand" ], "offsets": [ [ 1096, 1106 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6c52e2c3-37f2-46da-8aa1-501520fd093e", "type": "Gene", "text": [ "Fas ligand" ], "offsets": [ [ 1223, 1233 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3c8f72f1-f3f0-4f99-9434-18896a99f523", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 1337, 1348 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6382fdf0-74d2-4915-912e-ef647f46a03a", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 1430, 1441 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9b585363-401c-4bfd-9473-8807c4dd142a", "type": "Gene", "text": [ "Fas" ], "offsets": [ [ 1631, 1634 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "29c70f98-75ee-410f-abce-885c1557b65e", "type": "Gene", "text": [ "Fas ligand" ], "offsets": [ [ 1635, 1645 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "47b57e7e-8233-4bd6-9399-fb7a9bfcbcab", "type": "Gene", "text": [ "Fas antigen" ], "offsets": [ [ 1708, 1719 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "fe1bf0bc-e44e-4ed8-9737-993308d8dbd6", "type": "title", "text": [ "Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families." ], "offsets": [ [ 0, 81 ] ] }, { "id": "f84b003f-e2e4-4c6b-a5dc-727d2fb59030", "type": "abstract", "text": [ "The 999del5 mutation is the single, strong BRCA2 founder mutation in Iceland and the most common BRCA1/2 founder mutation in Finland. To evaluate the origin and time since spreading of the 999del5 mutation in Iceland and in Finland, we constructed haplotypes with polymorphic markers within and flanking the BRCA2 gene in a set of 18 Icelandic and 10 Finnish 999del5 breast cancer families. All Icelandic families analysed shared a common core haplotype of about 1.7 cM. The common ancestors for the Icelandic families studied were estimated to trace back to 340-1000 years, not excluding the possibility that the mutation was brought to Iceland during the settlement of the country. Analysis of the Finnish families revealed two distinct haplotypes. A rare one, found in three families in the old settlement region in southwestern Finland, shared a four-marker (0.5 cM) core haplotype with the Icelandic 999del5 haplotype. A distinct approximately 6 cM haplotype was shared by seven 999del5 Finnish families estimated to have a common ancestry 140-300 years ago. These families cluster in two geographical regions in Finland, in the very same area as those with the rare haplotype and also in the most eastern, late settlement region of Finland. The results may indicate a common ancient origin for the 999del5 mutation in Iceland and in Finland, but distinct mutational events cannot be ruled out. The surprising finding of the same mutation in two completely different haplotypes in a sparsely populated area in Finland may suggest gene conversion." ], "offsets": [ [ 82, 1633 ] ] } ]

[ { "id": "d06cef77-c123-4a05-86ec-9a72449c72a7", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 44, 49 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b5374734-310a-4285-ab7f-9a857ed3df6b", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 125, 130 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f92c4fa7-2a08-42e7-8520-7888418e5486", "type": "Gene", "text": [ "BRCA1/2" ], "offsets": [ [ 179, 186 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1976c966-b3b8-42e2-818d-80ae38ae0c86", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 390, 395 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c47c2653-3b51-4437-be7f-817f4da5a1e9", "type": "title", "text": [ "KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis." ], "offsets": [ [ 0, 151 ] ] }, { "id": "8e5e4ffe-e2f3-4a4c-9551-9fce39732e73", "type": "abstract", "text": [ "Mutations in KRIT1, a protein initially identified based on a yeast two-hybrid interaction with the RAS-family GTPase RAP1A, are responsible for the development of the inherited vascular disorder cerebral cavernous malformations (CCM1). As the function of the KRIT1 protein and its role in CCM pathogenesis remain unknown, we performed yeast two-hybrid screens to identify additional protein binding partners. A fragment containing the N-terminal 272 amino acid residues of KRIT1, a region lacking similarity to any known protein upon database searches, was used as bait. From parallel screens of human fetal brain and HeLa cDNA libraries, we obtained multiple independent isolates of human integrin cytoplasmic domain-associated protein-1 (ICAP-1) as interacting clones. The interaction of KRIT1 and ICAP-1 was confirmed by GST-KRIT1 trapping of endogenous ICAP-1 from 293T cells. The alpha isoform of ICAP-1 is a 200 amino acid serine/threonine-rich phosphoprotein which binds the cytoplasmic tail of beta1 integrins. We show that mutagenesis of the N-terminal KRIT1 NPXY amino acid sequence, a motif critical for ICAP-1 binding to beta1 integrin molecules, completely abrogates the KRIT1/ICAP-1 interaction. The interaction between ICAP-1 and KRIT1, and the presence of a FERM domain in the latter, suggest that KRIT1 might be involved in the bidirectional signaling between integrin molecules and the cytoskeleton. Furthermore, these data suggest that KRIT1 might affect cell adhesion processes via integrin signaling in CCM1 pathogenesis." ], "offsets": [ [ 152, 1695 ] ] } ]

[ { "id": "1d43eb43-4d10-4306-84ee-4a8ee86bc9ca", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 0, 5 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "95f3ce1a-963c-4544-9263-872c1c40ee4c", "type": "FamilyName", "text": [ "integrin-binding protein" ], "offsets": [ [ 27, 51 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "617619b2-42d5-4d07-9c41-df484b84293d", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 52, 58 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3383620c-eeb3-43de-aa85-24a2592d80e9", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 165, 170 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6a631e66-8b3d-47f4-aefe-d698b717c9d9", "type": "FamilyName", "text": [ "RAS" ], "offsets": [ [ 252, 255 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "379784eb-510c-4735-9793-8caaada141a6", "type": "FamilyName", "text": [ "GTPase" ], "offsets": [ [ 263, 269 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "91fe2902-5796-4aa3-ab8a-846cf661ba73", "type": "Gene", "text": [ "RAP1A" ], "offsets": [ [ 270, 275 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a70a814e-256e-4db9-8be6-c00bab1a6daf", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 412, 417 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0c1ddcd3-2f3f-4cb5-aff2-e8178772c804", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 626, 631 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e79f3e6a-1eb5-460b-8132-96468a8a0e78", "type": "Gene", "text": [ "integrin cytoplasmic domain-associated protein-1" ], "offsets": [ [ 843, 891 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "791de524-f902-46ab-9890-5182218bf905", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 893, 899 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "caec848c-7896-4b39-a5ed-b22df8299b92", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 943, 948 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "750063a8-1b10-4b52-8346-51ecfafc0be5", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 953, 959 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f39baad1-f3bb-4be9-8b17-ef0dbd6e8b28", "type": "FamilyName", "text": [ "GST" ], "offsets": [ [ 977, 980 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cd005392-572f-4f86-812e-96665c3c93ad", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 981, 986 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9e6bb04f-a575-457d-b60e-c6b29f938d93", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 1010, 1016 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5d7fb674-8958-471a-a68d-f704010f1946", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 1055, 1061 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "231545f3-6819-4c7e-b22e-3346f459056b", "type": "FamilyName", "text": [ "serine/threonine-rich phosphoprotein" ], "offsets": [ [ 1082, 1118 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "01db030e-3306-4933-bb04-3beb45fa9052", "type": "Gene", "text": [ "beta1 integrins" ], "offsets": [ [ 1155, 1170 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1cef0f84-149d-4265-a012-9704e80f8d34", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 1215, 1220 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a3e41172-adf8-4e4a-8d90-4e9f59b90d2a", "type": "DomainMotif", "text": [ "NPXY amino acid sequence" ], "offsets": [ [ 1221, 1245 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4a3ef7b4-063e-4bf2-8b3d-8a6b772a0e67", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 1268, 1274 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "62886d7e-a3c3-4f79-b04a-e75dca8ee6fa", "type": "Gene", "text": [ "beta1 integrin" ], "offsets": [ [ 1286, 1300 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "35b3094a-944a-463b-8ec4-af24101da819", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 1337, 1342 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f89ce51f-7a83-4c42-9daa-9726f2ddd6c0", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 1343, 1349 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ead1ed91-f566-495b-bce1-407763ab548a", "type": "Gene", "text": [ "ICAP-1" ], "offsets": [ [ 1387, 1393 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "213cdab0-8785-4919-8f03-96d6f9e6ad2d", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 1398, 1403 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "606a74ad-3913-43f2-b5c0-7a312769af3d", "type": "DomainMotif", "text": [ "FERM domain" ], "offsets": [ [ 1427, 1438 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fbbfe6b0-82d2-4a10-93c8-6ec0d277b56a", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 1467, 1472 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3665be04-fb24-4ee0-a47c-71c74b4db797", "type": "Gene", "text": [ "KRIT1" ], "offsets": [ [ 1608, 1613 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "db93d7bf-61f1-4e5f-9f33-3cf60c1e00f1", "type": "title", "text": [ "Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa." ], "offsets": [ [ 0, 132 ] ] }, { "id": "23d1eeea-9763-4d2d-b457-f68e1a6a3bff", "type": "abstract", "text": [ "Autosomal dominant retinitis pigmentosa (adRP) is a heterogeneous set of progressive retinopathies caused by several distinct genes. One locus, the RP10 form of adRP, maps to human chromosome 7q31.1 and may account for 5-10% of adRP cases among Americans and Europeans. We identified two American families with the RP10 form of adRP by linkage mapping and used these families to reduce the linkage interval to 3.45 Mb between the flanking markers D7S686 and RP-STR8. Sequence and transcript analysis identified 54 independent genes within this region, at least 10 of which are retinal-expressed and thus candidates for the RP10 gene. A screen of retinal transcripts comparing retinas from normal mice to retinas from crx-/crx- knockout mice (with poorly differentiated photoreceptors) demonstrated a 6-fold reduction in one candidate, inosine monophosphate dehydrogenase 1 (IMPDH1; EC 1.1.1.205). Since many of the genes known to cause retinitis pigmentosa are under CRX control in photoreceptors, IMPDH1 became a high-priority candidate for mutation screening. DNA sequencing of affected individuals from the two American RP10 families revealed a GAC-->AAC transition in codon 226 substituting an asparagine for an aspartic acid in both families. The identical mutation was also found in a British RP10 family. The Asp226Asn missense mutation is present in all affected individuals tested and absent from unaffected controls. The aspartic acid at codon 226 is conserved in all IMPDH genes, in all species examined, including bacteria, suggesting that this mutation is highly deleterious. Subsequent screening of probands from 60 other adRP families revealed an additional family with this mutation, confirming its association with retinitis pigmentosa and the relatively high frequency of this mutation. Another IMPDH1 substitution, Val268Ile, was also observed in this cohort of patients but not in controls. IMPDH1 is a ubiquitously expressed enzyme, functioning as a homotetramer, which catalyzed the rate-limiting step in de novo synthesis of guanine nucleotides. As such, it plays an important role in cyclic nucleoside metabolism within photoreceptors. Several classes of drugs are known to affect IMPDH isoenzymes, including nucleotide and NAD analogs, suggesting that small-molecule therapy may be available, one day, for RP10 patients." ], "offsets": [ [ 133, 2481 ] ] } ]

[ { "id": "141bce28-6be7-467d-9424-a136c5c6e05d", "type": "Gene", "text": [ "inosine monophosphate dehydrogenase 1" ], "offsets": [ [ 17, 54 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8caf7029-8c68-48a6-af02-18b9fbe53f03", "type": "Gene", "text": [ "IMPDH1" ], "offsets": [ [ 61, 67 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3f3226bc-d1a5-42a9-8cb2-0fc0a293a3a5", "type": "Gene", "text": [ "RP10" ], "offsets": [ [ 79, 83 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e9700178-4ea7-43f4-b192-026ee8657a87", "type": "FamilyName", "text": [ "Autosomal dominant retinitis pigmentosa" ], "offsets": [ [ 133, 172 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d5e75ef7-a908-4efc-b206-1a50f4407f36", "type": "FamilyName", "text": [ "adRP" ], "offsets": [ [ 174, 178 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7e3c2f88-74a8-4bbe-b6cf-f0bb528808d4", "type": "Gene", "text": [ "RP10" ], "offsets": [ [ 281, 285 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "42fd6968-ea13-460e-a695-0f196ad357c3", "type": "FamilyName", "text": [ "adRP" ], "offsets": [ [ 294, 298 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a2574288-0002-4af8-a877-50ed0816e5c8", "type": "FamilyName", "text": [ "adRP" ], "offsets": [ [ 361, 365 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f0bc41d7-9fca-429b-b097-a5e655079f24", "type": "Gene", "text": [ "RP10" ], "offsets": [ [ 448, 452 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "77d05831-5dfe-427c-96e6-e5a05a763673", "type": "FamilyName", "text": [ "adRP" ], "offsets": [ [ 461, 465 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6ba76156-f8ca-4083-a9e8-b439aab8f46f", "type": "Gene", "text": [ "RP10" ], "offsets": [ [ 756, 760 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f9ca7152-3531-48cb-9e44-bfdfa13a6a3f", "type": "Gene", "text": [ "crx" ], "offsets": [ [ 850, 853 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8406c59e-feaf-4e44-920f-edfa11dbb93a", "type": "Gene", "text": [ "crx" ], "offsets": [ [ 855, 858 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "324ab7e4-3a42-4509-9f4a-560ad343a629", "type": "Gene", "text": [ "inosine monophosphate dehydrogenase 1" ], "offsets": [ [ 968, 1005 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "10d99fd6-8a9b-45e8-82f9-c7ab85383f69", "type": "Gene", "text": [ "IMPDH1" ], "offsets": [ [ 1007, 1013 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f7c8a8bf-b085-4b0b-8ad4-c0a6c72d0285", "type": "Gene", "text": [ "CRX" ], "offsets": [ [ 1100, 1103 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f399b71a-c9a9-4752-9339-ade30ca96916", "type": "Gene", "text": [ "IMPDH1" ], "offsets": [ [ 1131, 1137 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "17621118-4b00-4ca6-8d88-65450055f34f", "type": "Gene", "text": [ "RP10" ], "offsets": [ [ 1256, 1260 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7739a8b2-7d7d-4141-b418-a20dcab3d6b1", "type": "Gene", "text": [ "RP10" ], "offsets": [ [ 1435, 1439 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2629fd80-f704-4ea1-b5a3-1210c3965279", "type": "FamilyName", "text": [ "IMPDH" ], "offsets": [ [ 1614, 1619 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c211f0df-f85c-4d80-88f8-70f9c974d370", "type": "FamilyName", "text": [ "adRP" ], "offsets": [ [ 1772, 1776 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5386b88c-7038-4def-93ed-c07030568a90", "type": "Gene", "text": [ "IMPDH1" ], "offsets": [ [ 1949, 1955 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9b7b529d-7679-4ec5-9b4c-b2b6caae0da4", "type": "Gene", "text": [ "IMPDH1" ], "offsets": [ [ 2047, 2053 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0df00838-6f09-4fc3-81ee-5d93d769480d", "type": "FamilyName", "text": [ "IMPDH" ], "offsets": [ [ 2341, 2346 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fffa2ae5-dae1-49b9-842a-0c1a006b0f7a", "type": "Gene", "text": [ "RP10" ], "offsets": [ [ 2467, 2471 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "7ca6519c-dd7b-4b5b-a190-04f4848149ed", "type": "title", "text": [ "Lead induced DNA strand breaks in lymphocytes of exposed workers: role of reactive oxygen species and protein kinase C." ], "offsets": [ [ 0, 119 ] ] }, { "id": "c3ebf558-b3c3-4f2e-a291-f3c9df7f217f", "type": "abstract", "text": [ "Lead and lead compounds play a significant role in modern industry; a wide variety of population is at risk of occupational exposure and lead is suspected to be a human carcinogen. The biochemical and molecular mechanisms of lead toxicity are poorly understood, but emerging data suggest that some of the effects of lead may be due to its interference with calcium in the activation of protein kinase C (PKC) and/or through production of reactive oxygen species (ROS). Many of these results are conducted in vitro on cell lines or ex vivo on human lymphocytes treated in vitro. We, therefore, performed a study on the induction of DNA damage, using the alkaline comet assay, in lymphocytes of battery plant workers. To elucidate in vivo the mechanism(s) responsible for this effect, we determined ROS production, and glutathione (GSH) levels in living cells using the fluorescent probe (2',7'-dichlorofluorescein and monochlorobimane, respectively). Subcellular fractions were obtained from sonicated lymphocytes; cytosolic and membrane expression of PKC isoforms (alpha, and zeta) was evaluated after electrophoresis by immunoblot analysis. The results indicate that lead-exposed workers have significantly elevated levels of DNA breaks compared to the unexposed group. A multivariate analysis of variance (ANOVA) shows that the most common confounding factors (smoking, drinking and age) have no synergistic effects with lead-exposure on the comet parameters or on GSH levels and ROS production. The logistic regression analysis distinguishing the exposed and non-exposed indicates that only GSH with tail moment are selected as significant risk factors. There is a significant positive correlation with ROS production and negative correlation with GSH levels. The content of PKC alpha in cytosol and membranes is decreased 40% (indicating a down-regulation of protein), whereas PKC zeta isoform is not modified in an evident manner. Our results suggest that lead-exposure induces an increase of DNA breakage with an alternate cellular redox state and a significant down-regulation of PKC alpha, suggesting that this metal may act as a tumor promoter." ], "offsets": [ [ 120, 2283 ] ] } ]

[ { "id": "5fd596ad-7806-47fc-b232-8f6525e202bf", "type": "FamilyName", "text": [ "protein kinase C" ], "offsets": [ [ 102, 118 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "267a54a8-cb0b-45e5-b72c-ee654b726ed0", "type": "FamilyName", "text": [ "protein kinase C" ], "offsets": [ [ 506, 522 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0621dbb9-56f7-41ad-bd7b-7535f7c6f70e", "type": "FamilyName", "text": [ "PKC" ], "offsets": [ [ 524, 527 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "651528ef-7119-4f99-9129-03dc24a5c693", "type": "Gene", "text": [ "PKC isoforms (alpha, and zeta)" ], "offsets": [ [ 1181, 1211 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6198b197-9e67-4e24-b6b8-8578b9318c6a", "type": "Gene", "text": [ "PKC alpha" ], "offsets": [ [ 1908, 1917 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4269906a-03eb-40aa-8768-f1ca0a550d3d", "type": "Gene", "text": [ "PKC zeta" ], "offsets": [ [ 2011, 2019 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "329e4bfe-0191-4bc2-89b7-ed2b4a21fd0e", "type": "Gene", "text": [ "PKC alpha" ], "offsets": [ [ 2217, 2226 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "4fde67cf-c828-4964-89bf-39e0a5ca9723", "type": "title", "text": [ "The pharmacogenetics of NAT: structural aspects." ], "offsets": [ [ 0, 48 ] ] }, { "id": "759198ab-4126-4bb1-a841-736ec6b11d3d", "type": "abstract", "text": [ "Arylamine N-acetyltransferases (NATs) catalyze the transfer of an acetyl group from acetyl-CoA to arylhydrazines and to arylamine drugs and carcinogens or to their N-hydroxylated metabolites. NAT plays an important role in detoxification and metabolic activation of xenobiotics and was first identified as the enzyme responsible for inactivation of the antitubercular drug isoniazid, an arylhydrazine. The rate of inactivation was polymorphically distributed in the population: the first example of interindividual pharmacogenetic variation. Polymorphism in NAT activity is primarily due to single nucleotide polymorphisms (SNPs) in the coding region of NAT genes. NAT enzymes are widely distributed in eukaryotes and genome sequences have revealed many homologous members of this enzyme family in prokaryotes. The structures of S almonella typhimurium and Mycobacterium smegmatis NATs have been determined, revealing a unique fold in which a catalytic triad (Cys-His-Asp) forms the active site. Determination of prokaryotic and eukaryotic NAT structures could lead to a better understanding of their role in xenobiotics and endogenous metabolism." ], "offsets": [ [ 49, 1196 ] ] } ]

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[ { "id": "ad6b7b2b-28a5-409a-8ace-4284ad448c92", "type": "title", "text": [ "Inherited and de novo mutations in sporadic cases of DYT1-dystonia." ], "offsets": [ [ 0, 67 ] ] }, { "id": "58058ac9-caf0-469a-8d8d-32794f6d2637", "type": "abstract", "text": [ "A study of Danish probands with primary torsion dystonia is presented. The probands were examined clinically and biochemically to exclude secondary dystonia. Mutation analyses for the GAG-deletion in the DYT1 gene were performed on 107 probands; and the mutation was detected in three. All three probands had the classical phenotype of DYT1-dystonia, but only one had a family history of dystonia. The other two probands had, obviously, sporadic DYT1-dystonia, one of which was caused by a de novo mutation, while the other one had a parent being an asymptomatic carrier. De novo mutations in the DYT1 gene are seldom reported although independent founder mutations are known to have occurred. The frequency of DYT1-dystonia was low in our study even though several probands had early onset generalised dystonia. None of the probands in our study with other types of dystonia had the GAG-deletion as reported in other studies. The difficulties in genetic counselling concerning the heterogeneity of dystonia exemplified by DYT1-dystonia are outlined." ], "offsets": [ [ 68, 1118 ] ] } ]

[ { "id": "d8c3a9d3-2214-4621-8e03-32b45afae833", "type": "Gene", "text": [ "DYT1" ], "offsets": [ [ 53, 57 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d4b5d893-57ce-4066-be2e-56226d3cab59", "type": "Gene", "text": [ "DYT1" ], "offsets": [ [ 272, 276 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9a08fcc8-5ce6-4030-8198-e6f232815793", "type": "Gene", "text": [ "DYT1" ], "offsets": [ [ 404, 408 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9d082f55-24aa-413c-8b9b-384e901b273d", "type": "Gene", "text": [ "DYT1" ], "offsets": [ [ 514, 518 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1bbee5ad-3d32-4241-bd56-9ff8aa44e575", "type": "Gene", "text": [ "DYT1" ], "offsets": [ [ 665, 669 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0b96e092-b908-472c-b87f-6c225e3df00f", "type": "Gene", "text": [ "DYT1" ], "offsets": [ [ 779, 783 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "884b8719-7db4-43b9-80a4-bab033428234", "type": "Gene", "text": [ "DYT1" ], "offsets": [ [ 1091, 1095 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "1a25e325-6cb0-4eb9-8a17-a9bdac78890e", "type": "title", "text": [ "The IARC TP53 database: new online mutation analysis and recommendations to users." ], "offsets": [ [ 0, 82 ] ] }, { "id": "7023496f-66b3-48fd-9402-fe957751315a", "type": "abstract", "text": [ "Mutations in the tumor suppressor gene TP53 are frequent in most human cancers. Comparison of the mutation patterns in different cancers may reveal clues on the natural history of the disease. Over the past 10 years, several databases of TP53 mutations have been developed. The most extensive of these databases is maintained and developed at the International Agency for Research on Cancer. The database compiles all mutations (somatic and inherited), as well as polymorphisms, that have been reported in the published literature since 1989. The IARC TP53 mutation dataset is the largest dataset available on the variations of any human gene. The database is available at www.iarc.fr/P53/. In this paper, we describe recent developments of the database. These developments include restructuring of the database, which is now patient-centered, with more detailed annotations on the patient (carcinogen exposure, virus infection, genetic background). In addition, a new on-line application to retrieve somatic mutation data and analyze mutation patterns is now available. We also discuss limitations on the use of the database and provide recommendations to users." ], "offsets": [ [ 83, 1246 ] ] } ]

[ { "id": "8d79ea4a-0866-4a3e-accb-187ea8ef94a3", "type": "Gene", "text": [ "TP53" ], "offsets": [ [ 9, 13 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "316018fa-7b47-4c49-84aa-38bac02e133b", "type": "FamilyName", "text": [ "tumor suppressor" ], "offsets": [ [ 100, 116 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "08415cae-76d5-438c-8b99-b92f97ae2745", "type": "Gene", "text": [ "TP53" ], "offsets": [ [ 122, 126 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "90f7626a-91fb-43e2-a8fe-279daab40de0", "type": "Gene", "text": [ "TP53" ], "offsets": [ [ 321, 325 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cb86844a-3f7a-47fe-9867-cf72592952ce", "type": "Gene", "text": [ "TP53" ], "offsets": [ [ 635, 639 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "e67a335a-f9b8-4e56-b392-26255d3af5c8", "type": "title", "text": [ "Human flavin-containing monooxygenase (form 3): polymorphisms and variations in chemical metabolism." ], "offsets": [ [ 0, 100 ] ] }, { "id": "4534eb24-2582-40bb-96b5-8cbeb26b2d6c", "type": "abstract", "text": [ "The human flavin-containing monooxygenases catalyze the oxygenation of nucleophilic heteroatom-containing drugs, xenobiotics and endogenous materials. Evidence for six forms of the FMO gene exist but it is FMO form 3 (FMO3) that is the prominent form in adult human liver that is likely to be associated with the bulk of FMO-mediated metabolism. An understanding of the substrate specificity of human FMO3 is beginning to emerge and several examples of drugs and chemicals extensively metabolized by FMO3 have been reported. Expression of FMO3 is species- and tissue-specific, but unlike human cytochrome P450 (CYP450), mammalian FMO3 does not appear to be inducible. Interindividual variation in FMO3-dependent metabolism of drugs, chemicals and endogenous materials is therefore more likely to be due to genetic and not environmental effects. Certain mutations of the human FMO3 gene have been associated with abnormal N-oxygenation of trimethylamine. Deficient N-oxygenation of trimethylamine results in a condition called trimethylaminuria. Some treatment strategies for this inborn error of metabolism are discussed. Other common variants of the FMO3 gene including E158K, V257M and E308G have been observed. It is possible that allelic variation of human FMO3 causes abnormal metabolism of chemicals and has clinical implications for human drug metabolism, but this is an understudied area. Human FMO3 allelic variation may eventually be shown to contribute to interindividual and interethnic variability in FMO3-mediated metabolism. Human FMO3 may be another example of an environmental gene that participates in a protective mechanism to help shield humans from potentially toxic exposure to chemicals. Heterogeneity in the relative frequencies of single and multiple site alleles, haplotypes and genotypes of the human FMO3 amongst various ethnic groups suggests population differences." ], "offsets": [ [ 101, 1996 ] ] } ]

[ { "id": "9f524c59-de01-4721-a17a-de5064baab67", "type": "Gene", "text": [ "flavin-containing monooxygenase (form 3)" ], "offsets": [ [ 6, 46 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4653268d-9d60-4b62-8276-c047693a4e17", "type": "FamilyName", "text": [ "FMO" ], "offsets": [ [ 282, 285 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a2bb0a54-25fd-43f4-bcca-230658f9ddfb", "type": "Gene", "text": [ "FMO form 3" ], "offsets": [ [ 307, 317 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cec5390f-2f75-47a4-a4e0-8ed483502647", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 319, 323 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "91a56829-d807-4b1f-8065-302fff814b72", "type": "FamilyName", "text": [ "FMO" ], "offsets": [ [ 422, 425 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b624980-f730-48f5-92a8-e361ab701fc7", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 502, 506 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0b4d6920-c417-4546-9dc9-79b7543508a0", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 601, 605 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "96f9a846-96ac-48d0-83a3-cfd677e8f585", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 640, 644 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2b2fe41c-3785-42cf-ad6d-e4479c490836", "type": "FamilyName", "text": [ "cytochrome P450" ], "offsets": [ [ 695, 710 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "67ccd2bb-de6d-4f35-bb61-e4351bd79b2c", "type": "FamilyName", "text": [ "CYP450" ], "offsets": [ [ 712, 718 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4fd1b8bc-c51b-4651-a4fe-a365dd976f5c", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 731, 735 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a1d873b0-0765-496a-90d5-84418a3cc471", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 798, 802 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "76ca7001-2885-4654-a7f9-49d632a49454", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 977, 981 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "376e7733-0ff4-4a92-9298-06b51c17fe32", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f928cefb-f317-432c-9279-07a4450fd544", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 1362, 1366 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ef9d7ffa-b118-4e4e-b4ac-64261bdd4132", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "796202dd-8ff8-4983-8069-c90133d02c49", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 1615, 1619 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9af0229b-f7f4-4cfe-8774-418693f9b7cd", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 1647, 1651 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "76cd8638-e1e7-403c-a131-5f191a73dfcb", "type": "Gene", "text": [ "FMO3" ], "offsets": [ [ 1929, 1933 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "0098275d-cd72-401b-a7f4-ff358170c46b", "type": "title", "text": [ "Twenty single-nucleotide polymorphisms in four genes encoding cardiac ion channels." ], "offsets": [ [ 0, 83 ] ] }, { "id": "1c024fc5-9e7e-4c06-aecd-080e4cd152aa", "type": "abstract", "text": [ "We here report 20 novel single-nucleotide polymorphisms in four genes that are potentially involved in the excitement of cardiomyocytes: 1 in KCNA5 (encoding Kv1.5), 5 in KCNAB1 (encoding Kvbeta1.3), 5 in KCNIP2 (encoding KChIP2), and 9 in CACNA1C (encoding a cardiac L-type voltage-dependent calcium ion channel, dihydropyridine receptor). We also examined their allelic frequencies in Japanese individuals. These data will be useful for genetic association studies designed to investigate secondary long QT syndrome or other circulatory disorders." ], "offsets": [ [ 84, 633 ] ] } ]

[ { "id": "ce067a8b-dfa2-4d02-931f-59cb807832c7", "type": "Gene", "text": [ "KCNA5" ], "offsets": [ [ 226, 231 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9b6ae1f9-f918-4b0b-9200-dffa2517c72a", "type": "Gene", "text": [ "Kv1.5" ], "offsets": [ [ 242, 247 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5cc89266-e0aa-46eb-a550-94d4fdf9135e", "type": "Gene", "text": [ "KCNAB1" ], "offsets": [ [ 255, 261 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "726d1a7e-59d5-4a94-a9ff-58c617f472ba", "type": "Gene", "text": [ "Kvbeta1.3" ], "offsets": [ [ 272, 281 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ea9acce0-1f7d-433e-96f4-ef74c81f1b58", "type": "Gene", "text": [ "KCNIP2" ], "offsets": [ [ 289, 295 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c7400aa0-bba0-47f8-bba8-a195bc8eddeb", "type": "Gene", "text": [ "KChIP2" ], "offsets": [ [ 306, 312 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "52da028e-4f69-41d8-9d8b-37a40586f9ed", "type": "Gene", "text": [ "CACNA1C" ], "offsets": [ [ 324, 331 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f1ef0f89-d4ef-4739-ba98-7d302312aded", "type": "FamilyName", "text": [ "cardiac L-type voltage-dependent calcium ion channel" ], "offsets": [ [ 344, 396 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1ffe8f1b-ad6e-454a-aae4-9178ca1242cb", "type": "FamilyName", "text": [ "dihydropyridine receptor" ], "offsets": [ [ 398, 422 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "753cbc8f-3e79-4c4a-ac64-737e2697fa4a", "type": "title", "text": [ "Vitreoretinopathy with phalangeal epiphyseal dysplasia, a type II collagenopathy resulting from a novel mutation in the C-propeptide region of the molecule." ], "offsets": [ [ 0, 156 ] ] }, { "id": "16a82757-be99-48ab-bb6f-9896622fda5f", "type": "abstract", "text": [ "A large family with dominantly inherited rhegmatogenous retinal detachment, premature arthropathy, and development of phalangeal epiphyseal dysplasia, resulting in brachydactyly was linked to COL2A1, the gene encoding proalpha1(II) collagen. Mutational analysis of the gene by exon sequencing identified a novel mutation in the C-propeptide region of the molecule. The glycine to aspartic acid change occurred in a region that is highly conserved in all fibrillar collagen molecules. The resulting phenotype does not fit easily into pre-existing subgroups of the type II collagenopathies, which includes spondyloepiphyseal dysplasia, and the Kniest, Strudwick, and Stickler dysplasias." ], "offsets": [ [ 157, 842 ] ] } ]

[ { "id": "2d438630-0418-4de1-8741-67ff2c3fb2ee", "type": "Gene", "text": [ "COL2A1" ], "offsets": [ [ 349, 355 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0b59a937-5595-4251-b1c8-0b0cbac114a4", "type": "Gene", "text": [ "proalpha1(II) collagen" ], "offsets": [ [ 375, 397 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "58c67af0-1b6d-47f8-ae2f-60f1230c72a5", "type": "title", "text": [ "Haplotype study of West European and North African Unverricht-Lundborg chromosomes: evidence for a few founder mutations." ], "offsets": [ [ 0, 121 ] ] }, { "id": "b4eec120-aec3-4399-b62c-4cf3feb2493b", "type": "abstract", "text": [ "Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy common in Finland and North Africa, and less common in Western Europe. ULD is mostly caused by expansion of a dodecamer repeat in the cystatin B gene ( CSTB) promoter. We performed a haplotype study of ULD chromosomes (ULDc) with the repeat expansion. We included 48 West European Caucasian (WEC) and 47 North African (NA) ULDc. We analysed eight markers flanking CSTB(GT10-D21S1890-D21S1885-D21S2040-D21S1259- CSTB-D21S1912-PFKL-D21S171) and one intragenic variant in the CSTB 3' UTR (A2575G). We observed a founder effect in most of the NA ULD patients, as 61.7% of the NA ULDc (29/47) shared the same haplotype, A1 (1-1-A-1-6-7), for markers D21S1885-D21S2040-A2575G-D21S1259-D21S1912-PFKL. Moreover, if we considered only the markers D21S1885, D21S2040, A2575G and D21S1259, 43 of the 47 NA ULDc shared the same alleles 1-1-A-1, haplotype A. As previously shown, the WEC ULDc were heterogeneous. However, the Baltic haplotype, A3 (5-1-1-A-1-1), was observed in ten WEC ULDc (20.8%) and the CSTB 3'UTR variant, which we called the Alps variant, was observed in 17 ULDc (35.4%). Finally, as almost all NA patients, like Scandinavian patients, were of the haplotype A, we assumed that there was an ancient common founder effect in NA and Baltic ULD patients. We estimated that the putative most recent common ancestral ULD carrier with this haplotype A must have existed about 2,500 years ago (100-150 generations). Finally, this work provides evidence for the existence of only a small number of founder mutations in ULD." ], "offsets": [ [ 122, 1725 ] ] } ]

[ { "id": "16af1d27-852f-43c9-89e5-8eea0d4be805", "type": "Gene", "text": [ "cystatin B" ], "offsets": [ [ 326, 336 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0b30d649-00b3-4201-b4e3-94788ec77e6a", "type": "Gene", "text": [ "CSTB" ], "offsets": [ [ 344, 348 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5c7694f8-6452-4434-b138-0ccb54c69ff6", "type": "Gene", "text": [ "CSTB" ], "offsets": [ [ 556, 560 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3c7d86dc-fec1-4894-b910-572ff28a3f97", "type": "Gene", "text": [ "CSTB" ], "offsets": [ [ 603, 607 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9c622be1-8ee4-4b75-bac9-350933dffa11", "type": "Gene", "text": [ "PFKL" ], "offsets": [ [ 617, 621 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fd305497-ff82-4a5e-b9dd-42736e64c211", "type": "Gene", "text": [ "CSTB" ], "offsets": [ [ 665, 669 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "84144064-1706-480b-9012-efe9de32d1db", "type": "Gene", "text": [ "PFKL" ], "offsets": [ [ 885, 889 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "969ff71b-271b-4457-b69a-042f3d4449d5", "type": "Gene", "text": [ "CSTB" ], "offsets": [ [ 1191, 1195 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "64742b64-0106-44fa-aca4-2de7b662429a", "type": "title", "text": [ "Three novel mutations of the PKD1 gene in Korean patients with autosomal dominant polycystic kidney disease." ], "offsets": [ [ 0, 108 ] ] }, { "id": "5887da67-9259-44b0-b393-f923079bd440", "type": "abstract", "text": [ "Mutations at the PKD1 locus account for 85% of cases of the common genetic disorder called autosomal dominant polycystic kidney disease (ADPKD). Screening for mutations of the PKD1 gene is complicated by the genomic structure of the 5'-duplicated region encoding 75% of the gene. To date, more than 90 mutations of the PKD1 gene have been reported in the European and American populations, and relatively little information is available concerning the pattern of mutations present in the Asian populations. We looked for mutations of the PKD1 gene in 51 unrelated Korean ADPKD patients, using polymerase chain reaction (PCR) with primer pairs located in the 3' single-copy region of the PKD1 gene and by single-strand conformation polymorphism (SSCP) analysis. We found three novel mutations, a G to A substitution at nucleotide 11012 (G3601S), a C to A substitution at nucleotide 11312 (Q3701X), and a C to T substitution at nucleotide 12971 (P4254S), and a single polymorphism involving a G to C substitution at nucleotide 11470 (L3753L). These mutations were not found in control individuals, and no other mutations in the 3' single-copy region of the PKD1 gene of patients with these mutations were observed. In particular, P4254S segregated with the disease phenotype. The clinical data of affected individuals from this study, and of previously reported Korean PKD1 mutations, showed that patients with frameshift or nonsense mutations were more prone to develop end-stage renal failure than those with missense mutations. Our findings indicate that many different PKD1 mutations are likely to be responsible for ADPKD in the Korean population, as in the Western population." ], "offsets": [ [ 109, 1804 ] ] } ]

[ { "id": "d791b8fd-d146-497f-9f38-0f0a010007e4", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 29, 33 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "14b1237c-a135-4bf5-8dc5-ddd8bc282e1a", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 126, 130 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2092c709-be9d-4bfc-bb2c-92e2ec76484c", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 285, 289 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "27181ed2-eec8-40d7-9322-38b1042df293", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 433, 437 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "defb414f-1897-4576-be73-4ee4a98d2b37", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 652, 656 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1a1c34af-df7c-483f-9275-3a1f7bdcfa98", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 806, 810 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "81a32395-99dc-4bc1-a8fc-2446a7385283", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 1279, 1283 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "93b7fcec-6218-457c-a999-147688ef8104", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 1491, 1495 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f22812d1-fc35-4617-b5e0-2bf31944f162", "type": "Gene", "text": [ "PKD1" ], "offsets": [ [ 1695, 1699 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "694dec8a-46f7-4a7f-8931-747f14f8fbc4", "type": "title", "text": [ "Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa." ], "offsets": [ [ 0, 103 ] ] }, { "id": "1c544cfe-a8df-4a1f-939d-d0c80a1b8611", "type": "abstract", "text": [ "Pseudoxanthoma elasticum (PXE) is a heritable elastic tissue disorder recently shown to be attributable to mutations in the ABCC6 ( MRP6) gene. Whereas PXE has been identified in all ethnic groups studied to date, the prevalence of this disease in various populations is uncertain, although often assumed to be similar. A notable exception however is the prevalence of PXE among South African Afrikaners. A previous report has suggested that a founder effect may explain the higher prevalence of PXE in Afrikaners, a European-derived population that first settled in South Africa in the 17th century. To investigate this hypothesis, we performed haplotype and mutational analysis of DNA from 24 South African families of Afrikaner, British and Indian descent. Among the 17 Afrikaner families studied, three common haplotypes and six different disease-causing variants were identified. Three of these mutant alleles were missense variants, two were nonsense mutations and one was a single base-pair insertion. The most common variant accounted for 53% of the PXE alleles, whereas other mutant alleles appeared at lower frequencies ranging from 3% to 12%. Haplotype analysis of the Afrikaner families showed that the three most frequent mutations were identical-by-descent, indicating a founder origin of PXE in this population." ], "offsets": [ [ 104, 1430 ] ] } ]

[ { "id": "582302fa-890e-4106-ae7f-8ab5b9c1f550", "type": "Gene", "text": [ "ABCC6" ], "offsets": [ [ 228, 233 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cb88ade5-cb74-4b14-b562-1d087780a382", "type": "Gene", "text": [ "MRP6" ], "offsets": [ [ 236, 240 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "be231ef9-df5b-458c-a560-17152b2ccf41", "type": "title", "text": [ "D90A-SOD1 mediated amyotrophic lateral sclerosis: a single founder for all cases with evidence for a Cis-acting disease modifier in the recessive haplotype." ], "offsets": [ [ 0, 156 ] ] }, { "id": "7b83d356-1437-406b-a45e-f4c1dbbbf08b", "type": "abstract", "text": [ "More than 100 different heterozygous mutations in copper/zinc superoxide dismutase (SOD1) have been found in patients with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Uniquely, D90A-SOD1 has been identified in recessive, dominant and apparently sporadic pedigrees. The phenotype of homozygotes is stereotyped with an extended survival, whereas that of affected heterozygotes varies. The frequency of D90A-SOD1 is 50 times higher in Scandinavia (2.5%) than elsewhere, though ALS prevalence is not raised there. Our earlier study indicated separate founders for recessive and dominant/sporadic ALS and we proposed a disease-modifying factor linked to the recessive mutation. Here we have doubled our sample set and employed novel markers to characterise the mutation's origin and localise any modifying factor. Linkage disequilibrium analysis indicates that D90A homozygotes and heterozygotes share a rare haplotype and are all descended from a single ancient founder (alpha 0.974) c.895 generations ago. Homozygotes arose subsequently only c.63 generations ago (alpha 0.878). Recombination has reduced the region shared by recessive kindreds to 97-265 kb around SOD1, excluding all neighbouring genes. We propose that a cis-acting regulatory polymorphism has arisen close to D90A-SOD1 in the recessive founder, which decreases ALS susceptibility in heterozygotes and slows disease progression." ], "offsets": [ [ 157, 1582 ] ] } ]

[ { "id": "feccb20f-a5e8-4bad-991f-aed1606563b4", "type": "Gene", "text": [ "SOD1" ], "offsets": [ [ 5, 9 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "89d92184-e3ef-4d38-879d-490d1066c7a2", "type": "FamilyName", "text": [ "copper/zinc superoxide dismutase" ], "offsets": [ [ 207, 239 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "113ce8c4-2efe-414b-8654-31e923e4d78d", "type": "Gene", "text": [ "SOD1" ], "offsets": [ [ 241, 245 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "053b8500-3746-4957-aa6b-f5549686152e", "type": "Gene", "text": [ "SOD1" ], "offsets": [ [ 367, 371 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d77565b2-4e8f-4d19-84af-1673ea9cd11e", "type": "Gene", "text": [ "SOD1" ], "offsets": [ [ 590, 594 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "18216f15-7289-4018-bbd2-e04197e43c78", "type": "Gene", "text": [ "SOD1" ], "offsets": [ [ 1351, 1355 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "68688b41-061d-4081-9a71-ff7ce4b1af74", "type": "Gene", "text": [ "SOD1" ], "offsets": [ [ 1469, 1473 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "8d122561-2820-4221-a91d-27ec7da2990c", "type": "title", "text": [ "SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with cardiac arrhythmias and sudden death in a white family." ], "offsets": [ [ 0, 126 ] ] }, { "id": "39f211ed-c376-40d9-b2dc-70e9659c1413", "type": "abstract", "text": [ "Cardiac arrhythmias cause 400 000 sudden deaths annually in the United States alone. Mutations in the cardiac sodium channel gene SCN5A on chromosome 3p21 cause cardiac arrhythmias and sudden death. In this study, we define an SCN5A mutation, S1103Y, in a white family associated with syncope, ventricular fibrillation, and sudden death. A very recent study reported the same mutation in 13.2% of African Americans, but not in the white population. Our study shows that mutation S1103Y does exist in the white population, and it is associated with a considerable risk of syncope, ventricular arrhythmia, ventricular fibrillation, and sudden death in this population." ], "offsets": [ [ 127, 793 ] ] } ]

[ { "id": "eeb69b1f-31c0-468f-972b-f8f9e63e7bd9", "type": "FamilyName", "text": [ "cardiac sodium channel gene" ], "offsets": [ [ 18, 45 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "66a32a99-4a7e-4273-b2f1-da463b63cd0d", "type": "Gene", "text": [ "SCN5A" ], "offsets": [ [ 46, 51 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6f0a062a-ef3e-42de-989b-af1b4c0ac642", "type": "FamilyName", "text": [ "cardiac sodium channel gene" ], "offsets": [ [ 229, 256 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9b4c9933-d592-493c-bffc-ade855ef6cf4", "type": "Gene", "text": [ "SCN5A" ], "offsets": [ [ 257, 262 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2d1d913d-651d-4f0e-a6bd-145a3001034e", "type": "Gene", "text": [ "SCN5A" ], "offsets": [ [ 354, 359 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "b3d329dd-c9d0-4f9f-b259-d69459184747", "type": "title", "text": [ "Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk." ], "offsets": [ [ 0, 110 ] ] }, { "id": "fc4edff2-6032-4909-96ee-d7362b54eca6", "type": "abstract", "text": [ "Rare germline mutations of macrophage scavenger receptor 1 (MSR1) gene were reported to be associated with prostate cancer risk in families with hereditary prostate cancer (HPC) and in patients with non-HPC (Xu et al. 2002). To further evaluate the role of MSR1 in prostate cancer susceptibility, at Johns Hopkins Hospital, we studied five common variants of MSR1 in 301 patients with non-HPC who underwent prostate cancer treatment and in 250 control subjects who participated in prostate cancer-screening programs and had normal digital rectal examination and PSA levels (<4 ng/ml). Significantly different allele frequencies between case subjects and control subjects were observed for each of the five variants (P value range.01-.04). Haplotype analyses provided consistent findings, with a significant difference in the haplotype frequencies from a global score test (P=.01). Because the haplotype that is associated with the increased risk for prostate cancer did not harbor any of the known rare mutations, it appears that the observed association of common variants and prostate cancer risk are independent of the effect of the known rare mutations. These results consistently suggest that MSR1 may play an important role in prostate carcinogenesis." ], "offsets": [ [ 111, 1371 ] ] } ]

[ { "id": "8df423fc-6c2b-4470-80f7-68805af2989d", "type": "Gene", "text": [ "macrophage scavenger receptor 1" ], "offsets": [ [ 32, 63 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7f67c147-0f58-40eb-b47b-f5b5ce604280", "type": "Gene", "text": [ "macrophage scavenger receptor 1" ], "offsets": [ [ 138, 169 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c5ce379f-e3bc-44d6-82b9-f4e1abd119c8", "type": "Gene", "text": [ "MSR1" ], "offsets": [ [ 171, 175 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "52d7b8d0-63c7-4cf8-a746-e1ac8eabaa8b", "type": "Gene", "text": [ "MSR1" ], "offsets": [ [ 368, 372 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2ea073bb-3b03-4254-a568-f9fe7f95f18a", "type": "Gene", "text": [ "MSR1" ], "offsets": [ [ 470, 474 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f25190d7-4c7f-4c2c-9c24-1cfce8df1ee1", "type": "Gene", "text": [ "PSA" ], "offsets": [ [ 673, 676 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "779ae657-1895-4cb9-9713-aca314644af7", "type": "Gene", "text": [ "MSR1" ], "offsets": [ [ 1312, 1316 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "aecbf94c-aa72-41e7-8b3b-d1865fea18b9", "type": "title", "text": [ "Subcortical band heterotopia with simplified gyral pattern and syndactyly." ], "offsets": [ [ 0, 74 ] ] }, { "id": "343a8d82-7cb9-48d0-8ec1-605ba6cce266", "type": "abstract", "text": [ "We describe a girl with an unusual form of subcortical band heterotopia (SBH) and a complex malformation syndrome. SBH had an irregular inner margin, organized in contiguous fascicles of migrating neurons, sometimes giving the appearance of many small contiguous gyri. The true cortex had decreased thickness and showed a simplified gyral pattern with decreased number of gyri, which were usually of increased width, and shallow sulci. The cerebellum was hypoplastic. Additional features included epicanthal folds, hypertelorism, small nose with hypoplastic nares, bilateral syndactyly of the toes, pulmonary valve stenosis, atrial and ventricular septal defects. At the age of 1 year the patient had severe developmental delay and epilepsy. Chromosome studies and mutation analysis of the DCX and LIS1 genes gave negative results. This observation delineates a new multiple congenital abnormalities mental retardation syndrome and confirms genetic heterogeneity of SBH." ], "offsets": [ [ 75, 1045 ] ] } ]

[ { "id": "85c05b4f-4a18-4472-8a27-a2a8ef94d2e9", "type": "Gene", "text": [ "DCX" ], "offsets": [ [ 865, 868 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6015c2f6-ca0e-4596-b9b4-426b07b4748a", "type": "Gene", "text": [ "LIS1" ], "offsets": [ [ 873, 877 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "28b456bb-d872-4f28-af86-6b4ff40aa68b", "type": "title", "text": [ "Lack of association between the G protein beta3 subunit gene and essential hypertension in Chinese: a case-control and a family-based study." ], "offsets": [ [ 0, 140 ] ] }, { "id": "8b62a143-af0c-43fa-a6be-59d878b737bc", "type": "abstract", "text": [ "A C825T polymorphism of the gene encoding the G protein beta3 subunit (GNB3) is associated with enhanced G protein activity and increased intracellular signal transduction. The 825T allele has been implicated in the development of hypertension in some ethnic groups, especially in whites. Studies in Asians and blacks are more controversial, and little information is available on this polymorphism in the susceptibility to hypertension in the Chinese population. Furthermore, the inconsistency between studies may be due to genetic heterogeneity of the population selected and/or the lack of statistical power. We investigated the relationship of this polymorphism with hypertension in two independent northern Chinese populations using both a case-control and a family-based study design. The GNB3 C825T polymorphism was determined by polymerase chain reaction and restriction enzyme digestion. In the case-control study which included 585 hypertensive case subjects and 580 normotensive control subjects there was no significant association between the polymorphism and hypertension status or blood pressure levels. The lack of association was confirmed by the results obtained in 181 hypertensive families using both transmission disequilibrium test and sib transmission disequilibrium test. No preferential transmission was observed for the GNB3 825T allele to the affected subjects. Furthermore, there was no significant association between the polymorphism and body mass index in the case-control study. Therefore our work does not provide evidence in favor of GNB3 C825T being a candidate gene for conferring genetic susceptibility to hypertension or obesity in northern Chinese population." ], "offsets": [ [ 141, 1839 ] ] } ]

[ { "id": "16b0ff47-ccec-410e-8ac1-8c009ba6e84f", "type": "Gene", "text": [ "G protein beta3" ], "offsets": [ [ 32, 47 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fcb5da96-745f-4661-8ad3-267204262dff", "type": "Gene", "text": [ "G protein beta3" ], "offsets": [ [ 187, 202 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e5e9bf05-4821-4d8b-8ee9-1af519625d08", "type": "Gene", "text": [ "GNB3" ], "offsets": [ [ 212, 216 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "16c713c8-ec3c-470b-a580-152fcd174778", "type": "FamilyName", "text": [ "G protein" ], "offsets": [ [ 246, 255 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "43120bab-ee5a-4f65-9b81-0668f6911475", "type": "Gene", "text": [ "GNB3" ], "offsets": [ [ 936, 940 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b431d24d-299c-4669-977a-65947de8d021", "type": "Gene", "text": [ "GNB3" ], "offsets": [ [ 1487, 1491 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4630110b-821d-4e73-86eb-faa856ce3755", "type": "Gene", "text": [ "GNB3" ], "offsets": [ [ 1709, 1713 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "199b3625-9aae-4331-a038-4e13296e4360", "type": "title", "text": [ "Gene-gene interaction between the monoamine oxidase A gene and solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 gene in anorexia nervosa (restrictive subtype)." ], "offsets": [ [ 0, 188 ] ] }, { "id": "7bfac6fe-17a6-406e-a2b6-f7d0af71f436", "type": "abstract", "text": [ "We earlier found an association between anorexia nervosa (AN) restrictive subtype (AN-R) and an inserted sequence within the NETpPR, a polymorphic region located in the promoter of the solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 (SLC6A2) gene. To further examine the noradrenergic system in AN-R we performed an association study with a functional polymorphism (MAOA-uVNTR) in the promoter of the monoamine oxidase A (MAOA) gene. Since monoamine oxidase A metabolises noradrenalin, a positive association with the MAOA gene would be biologically plausible. The transmission disequilibrium test and 95 trios/duos (AN-R females+biological parents) showed the main effect of the longer, more transcriptionally active form of the MAOA-uVNTR (MAOA-L) to be statistically non-significant (McNemar's chi(2)=1.4, df=1, P=0.238, odds ratio: 1.4, 95% CI 0.8-2.7). A case-control approach supported this finding. We then stratified the MAOA-uVNTR TDT data according to the (a) NETpPR genotype of the AN-R females, and (b) NETpPR allele transmitted from NETpPR-S4/L4 heterozygous mothers. In both cases, contingency table analysis revealed previously unreported gene-gene interaction between the MAOA and SLC6A2 genes (P=0.019 and 0.019, respectively). Receiving an MAOA-L allele more than doubles the risk for developing AN-R, conditional on an individual also being a NETpPR-L4 homozygote (stratum-specific odds ratio: 2.4, 95% CI 1.1-6.0). These results suggest important involvement of the noradrenergic system in the biological underpinnings of AN-R." ], "offsets": [ [ 189, 1771 ] ] } ]

[ { "id": "14f0013b-e40a-4dce-ab40-6a48923ee58c", "type": "Gene", "text": [ "monoamine oxidase A" ], "offsets": [ [ 34, 53 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "af7ae46f-66f5-4f99-9928-4b16479e1d1e", "type": "Gene", "text": [ "solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2" ], "offsets": [ [ 63, 140 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0bfd2d28-f88f-42ed-8558-1624d3d9398a", "type": "Gene", "text": [ "solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2" ], "offsets": [ [ 374, 451 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fc9267f6-5453-4fe6-a936-3591845c8211", "type": "Gene", "text": [ "SLC6A2" ], "offsets": [ [ 453, 459 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "daaf943c-ae02-4dd6-92b9-c95bfce41310", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 585, 589 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "76f361ac-cb7e-47a3-abc5-b05874d92f32", "type": "Gene", "text": [ "monoamine oxidase A" ], "offsets": [ [ 620, 639 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8bebbec6-cd3c-4502-86a7-696c23f00ade", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 641, 645 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "072e5e3c-be96-4a24-8c10-16c032bea89e", "type": "Gene", "text": [ "monoamine oxidase A" ], "offsets": [ [ 659, 678 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5ab85a14-ad02-40a5-b487-11c3824affd2", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 737, 741 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7ac12294-6cf6-4bc5-ada4-aa9bc621b9c8", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 949, 953 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "85425dab-49b3-4939-89f2-0b7820e37ef9", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 961, 965 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "85641d86-e6a5-4a61-98f7-4581c46f2687", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 1153, 1157 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2cbc475e-3a82-47ae-8f36-e4505a1decb5", "type": "Gene", "text": [ "TDT" ], "offsets": [ [ 1164, 1167 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b2ee5e47-7416-4085-b6b2-f036d7ce0796", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 1412, 1416 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "248c2a44-2490-4395-9230-1b5b30fc2f57", "type": "Gene", "text": [ "SLC6A2" ], "offsets": [ [ 1421, 1427 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8356be5f-15f4-408a-a4b6-1a4c67f8ba68", "type": "Gene", "text": [ "MAOA" ], "offsets": [ [ 1482, 1486 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "e4ea5ab3-db43-496e-a6b9-dbc492868555", "type": "title", "text": [ "Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population." ], "offsets": [ [ 0, 97 ] ] }, { "id": "ea1c55a9-00b3-4c4c-945a-9e0f8fe323c7", "type": "abstract", "text": [ "The genetic basis of cardiovascular disease (CVD) with its complex etiology is still largely elusive. Plasma levels of lipids and apolipoproteins are among the major quantitative risk factors for CVD and are well-established intermediate traits that may be more accessible to genetic dissection than clinical CVD end points. Chromosome 19 harbors multiple genes that have been suggested to play a role in lipid metabolism and previous studies indicated the presence of a quantitative trait locus (QTL) for cholesterol levels in genetic isolates. To establish the relevance of genetic variation at chromosome 19 for plasma levels of lipids and apolipoproteins in the general, out-bred Caucasian population, we performed a linkage study in four independent samples, including adolescent Dutch twins and adult Dutch, Swedish and Australian twins totaling 493 dizygotic twin pairs. The average spacing of short-tandem-repeat markers was 6-8 cM. In the three adult twin samples, we found consistent evidence for linkage of chromosome 19 with LDL cholesterol levels (maximum LOD scores of 4.5, 1.7 and 2.1 in the Dutch, Swedish and Australian sample, respectively); no indication for linkage was observed in the adolescent Dutch twin sample. The QTL effects in the three adult samples were not significantly different and a simultaneous analysis of the samples increased the maximum LOD score to 5.7 at 60 cM pter. Bivariate analyses indicated that the putative LDL-C QTL also contributed to the variance in ApoB levels, consistent with the high genetic correlation between these phenotypes. Our study provides strong evidence for the presence of a QTL on chromosome 19 with a major effect on LDL-C plasma levels in outbred Caucasian populations." ], "offsets": [ [ 98, 1838 ] ] } ]

[ { "id": "a655949f-2023-4233-991e-e04dd86a87c9", "type": "Gene", "text": [ "ApoB" ], "offsets": [ [ 1600, 1604 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "ed2a6986-6a70-46c2-96ad-85c4478465e5", "type": "title", "text": [ "A 3.4-kbp transcript of ZNF331 is solely expressed in follicular thyroid adenomas." ], "offsets": [ [ 0, 82 ] ] }, { "id": "6a02a4ff-5f4c-4fce-8381-abef22ec543e", "type": "abstract", "text": [ "Translocations involving chromosomal region 19q13 are a frequent finding in follicular adenomas of the thyroid and might represent the most frequent type of structural aberration in human epithelial tumors. By positional cloning, a putative candidate gene, ZNF331 (formerly RITA) located close to the breakpoint was identified. Recently, aberrant expression of ZNF331 has been described in two cell lines of follicular thyroid adenomas with aberrations in 19q13 indicating an involvement of ZNF331 in tumorigenesis. Nevertheless, knowledge about structure and expression of ZNF331 is limited. We performed RACE-PCR and genomic sequence analyses to gain a deeper insight into its molecular structure. To elucidate ZNF331 expression patterns we performed Northern blot analyses on various normal tissues as well as on thyroid carcinoma and adenoma cell lines. Herein, unique expression of a 3.4-kbp transcript is described in thyroid adenoma cell lines with 19q13 aberrations, which was not detected either in normal tissues or in thyroid carcinoma cell lines." ], "offsets": [ [ 83, 1141 ] ] } ]

[ { "id": "56f63d66-09c8-48e8-9091-bcb7a9d52d30", "type": "Gene", "text": [ "ZNF331" ], "offsets": [ [ 24, 30 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b640c69a-c7a8-460c-bc37-1da7bb98407a", "type": "Gene", "text": [ "ZNF331" ], "offsets": [ [ 340, 346 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1c59eaf2-9f19-4440-9d3d-e6048ce25269", "type": "Gene", "text": [ "RITA" ], "offsets": [ [ 357, 361 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fe6b1f4c-cfac-4c07-825c-0f46813c7508", "type": "Gene", "text": [ "ZNF331" ], "offsets": [ [ 444, 450 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2b292801-9f79-4b09-b1c6-d28efabb02e7", "type": "Gene", "text": [ "ZNF331" ], "offsets": [ [ 574, 580 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8dc35fc0-197d-4ae9-8b89-48c016abe9e1", "type": "Gene", "text": [ "ZNF331" ], "offsets": [ [ 657, 663 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "33cdb9b7-f037-4b46-a40e-14c82cfcf925", "type": "Gene", "text": [ "ZNF331" ], "offsets": [ [ 796, 802 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "7aa2d1e8-446b-46eb-a782-5715cb5fe3b2", "type": "title", "text": [ "Developmentally-programmed FMRP expression in oligodendrocytes: a potential role of FMRP in regulating translation in oligodendroglia progenitors." ], "offsets": [ [ 0, 146 ] ] }, { "id": "a51a6ba3-59db-4ddb-8c74-8b11562a920b", "type": "abstract", "text": [ "The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein whose function is implicated in regulating protein synthesis of its mRNA targets. The lack of FMRP leads to abnormal synapse development in the brain and impaired learning/memory. Although FMRP is predominantly expressed in neurons of the adult brain, whether FMRP also functions in glia during early development remains elusive, since expression of FMRP in glia has not been rigorously examined. This is an important question because recent studies revealed important roles of glia in synaptic development. Here we report that in addition to the observed neuronal expression, FMRP expression is detected in oligodendroglia progenitor cells (OPCs), immature oligodendrocytes and oligodendroglia cell lines, where it interacts with a subgroup of oligodendrocyte-specific mRNAs, including the myelin basic protein (MBP) mRNA. FMRP expression gradually declines as oligodendrocytes differentiate in vitro and in the developing brain. The decline of FMRP expression during oligodendrocyte differentiation is associated with a vigorous up-regulation of the MBP protein. In addition, we show that the MBP 3'untranslated region (3'UTR) is necessary and sufficient for binding FMRP, and mediates translation inhibition of a reporter gene by FMRP specifically in oligodendrocytes. These results support the hypothesis that FMRP may participate in regulating translation of its bound mRNAs in oligodendroglia during early brain development." ], "offsets": [ [ 147, 1670 ] ] } ]

[ { "id": "d69de8c5-6d09-4bf2-abbf-7b84453612a7", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 27, 31 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9f93cbe6-5541-4701-8eb7-b3815ab52862", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 84, 88 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c244fe74-463f-4352-b132-838db5145725", "type": "Gene", "text": [ "fragile X mental retardation protein" ], "offsets": [ [ 151, 187 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bb7fb23a-704b-4e39-a29b-8872672bfb06", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 189, 193 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6b4f14bd-89cd-4592-a5b6-aa6aa470907f", "type": "FamilyName", "text": [ "RNA-binding protein" ], "offsets": [ [ 210, 229 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "54320a2b-4289-4bca-9270-2476f27d359f", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 324, 328 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "62064a05-df54-41c4-a112-c0c0cbaaffa9", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 419, 423 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8d174225-71ae-4c10-a51e-8957715df5e0", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 490, 494 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a6a351d5-a427-401a-a5e4-6de9b3693d98", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 580, 584 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2d2a805c-7404-4bdb-ade7-4e799012524c", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 807, 811 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dba40003-f314-4a3e-8e6b-79751cb82362", "type": "Gene", "text": [ "myelin basic protein" ], "offsets": [ [ 1021, 1041 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "73998b07-1583-4142-8c66-40f9d47ebf47", "type": "Gene", "text": [ "MBP" ], "offsets": [ [ 1043, 1046 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0855427c-74fe-4952-a4d4-17f6b1ab7d9a", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 1054, 1058 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "30f0bf07-4614-4eae-86c1-61bdacaa7bcd", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 1176, 1180 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fa986d48-426c-49df-bf78-39f34ff6e2dc", "type": "Gene", "text": [ "MBP" ], "offsets": [ [ 1282, 1285 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6a6297af-3269-4528-a40d-88c2699f56c8", "type": "Gene", "text": [ "MBP" ], "offsets": [ [ 1325, 1328 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b4fefd0b-c3c7-4856-825c-da15d78d8678", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 1409, 1413 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ef29a1ae-cdea-4c41-856d-e475ec4ee8f5", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 1473, 1477 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d7fb0df7-6484-4d40-ac87-341edfbe8124", "type": "Gene", "text": [ "FMRP" ], "offsets": [ [ 1554, 1558 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "469b0398-f954-484a-9de8-da053dd85d5f", "type": "title", "text": [ "Propofol anesthesia in children does not induce sister chromatid exchanges in lymphocytes." ], "offsets": [ [ 0, 90 ] ] }, { "id": "e0bfe66f-88c0-4ed1-b8c3-ffe24dd5cd3e", "type": "abstract", "text": [ "BACKGROUND: Propofol is frequently used for general anesthesia in children although little is known about possible genotoxic effects in humans. We investigated the formation of sister chromatid exchanges (SCE) in metaphase chromosomes of T-lymphocytes of children as a marker for possible genotoxocity following total intravenous anesthesia with propofol for minor surgical procedures. METHODS: 40 children ASA classification I-III were included (ASA I n=34, ASA II n=5, ASA III n=1) in the study. Anesthesia was induced by propofol (3mg/kg) and alfentanil. Succinylcholine or rocuronium were administered for muscle relaxation. After tracheal intubation anesthesia was maintained by continuous propofol infusion at 12 mg/(kgh). Blood samples were drawn before induction and after termination of anesthesia. Following a 72 h cell culture period, 25 T-lymphocyte metaphases per blood sample for all children were analyzed for SCE frequencies. RESULTS: Total intravenous anesthesia with propofol on children did not influence SCE rates in metaphase chromosomes of T-lymphocytes. No SCE differences could be detected between blood samples before initiation and after termination of anesthesia (Wilcoxon signed rank test). Slightly elevated SCE rates were obtained in T-lymphocytes of girls compared to boys, but these differences did not reach statistical significance. CONCLUSIONS: Propofol anesthesia under the chosen conditions did not induce the formation of SCE in children in vivo. No genotoxic effect of a short term exposure to propofol during pediatric anesthesia had been observed." ], "offsets": [ [ 91, 1679 ] ] } ]

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[ { "id": "64744c9b-537c-4237-a763-ec13cc78b477", "type": "title", "text": [ "Y-chromosomal microsatellite mutation rates: differences in mutation rate between and within loci." ], "offsets": [ [ 0, 98 ] ] }, { "id": "7027945d-604f-41db-8d53-c61391ac1b98", "type": "abstract", "text": [ "Precise estimates of mutation rates at Y-chromosomal microsatellite STR (short tandem repeat) loci make an important basis for paternity diagnostics and dating of Y chromosome lineage origins. There are indications of considerable locus mutation rate variability between (inter-) and within (intra-) loci. We have studied nine Y-STR loci-DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385, and DYS388-in 1,766 father-son pairs of confirmed paternity (a total of 15,894 meioses). Five biallelic markers were also analyzed in the fathers-Tat, YAP, 12f2, SRY1532, and 92R7-defining haplogroups 1, 2, 3, 4, 9, and 16, respectively. A total of 36 fragment length mutations were observed: 24 gains (22 single-step, two double-step) and 12 single-step losses. Thus, there was a significant surplus of gains (p=0.045). Overall, the mutation rate was positively correlated to STR repeat length and there was a significant relative excess of losses in long alleles and gains in short alleles (p=0.043). In contrast to the situation in autosomal STR loci and in MSY-1, no noteworthy correlation between mutation rate and the father's age at the child's birth was observed. We observed significant interlocus differences in Y-STR mutation rates (p<0.01). The number of observed mutations ranged from zero in DYS392 to eight in DYS391 and DYS390. We have also demonstrated obvious differences in mutation rates between the haplogroups studied (p=0.024), a phenomenon that is a reflection of the dependence of mutation rate on allele size. Our study has thus demonstrated the necessity of not only locus-specific, but even allele-specific, mutation rate estimates for forensic and population genetic purposes, and provides a considerable basis for such estimates." ], "offsets": [ [ 99, 1868 ] ] } ]

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[ { "id": "f0d25e61-1180-4ad0-8a43-e88de4d8c5b8", "type": "title", "text": [ "Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants." ], "offsets": [ [ 0, 94 ] ] }, { "id": "136b1a2f-901a-4578-bbea-3ef23fb2cc31", "type": "abstract", "text": [ "A large proportion of non-syndromic autosomal recessive deafness (NSARD) in many populations is caused by variants of the GJB2 gene. Here, the frequency of GJB2 variants was studied in 406 and 183 apparently unrelated children from Kenya and Sudan, respectively, with mostly severe to profound non-syndromic deafness. Nine (2.2 %) Kenyan and 12 (6.6 %) of the Sudanese children only were carriers of variants within the coding sequence of the GJB2 gene. Variants in the 5'-adjacent region were detected in further 115 individuals. A total of 10 novel variants was recognized, among them four variants in the adjacent 5'-region of the GJB2 coding exon 2 (g.3318-6T>A, g.3318-15C>T, g.3318-34C>T, g.3318-35T>G), a 6 base-pair deletion (g.3455_3460del [p.Asp46_Gln48delinsGlu]), a variant leading to a stop codon (g.3512C>A [p.Tyr65X]), synonymous variants (g.3395C>T [p.Thr26], g.3503C>T [p.Asn62], g.3627A>C [p.Arg104]), and one non-synonymous variant (g.3816C>A [p.Val167Met]). In addition, the previously described variants g.3352delG (commonly designated 30delG or 35 delG), g.3426G>A [p.Val37Ile], g.3697G>A [p.Arg127His], g.3774G>A [p.Val153Ile], and g.3795G>A [p.Gly160Ser] were identified. With the exception of g.3318-34C>T and g.3352delG, all variants occurred heterozygously. For most of the variants identified in the Kenyan and Sudanese study population, a causative association with NSARD appears to be unlikely. Compared to many other ethnic groups, deafness-associated variants of the coding region of GJB2 are rare in Sudan and Kenya, suggesting a role of other genetic, or epigenetic factors as a cause for deafness in these countries." ], "offsets": [ [ 95, 1798 ] ] } ]

[ { "id": "95d888ec-faf0-4082-8898-530c77ca9abd", "type": "Gene", "text": [ "GJB2" ], "offsets": [ [ 37, 41 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "39f65097-3fd8-44ba-9fd5-5ebcd15443e0", "type": "Gene", "text": [ "GJB2" ], "offsets": [ [ 80, 84 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dd3fa20e-c10e-4d4e-b91e-5f5adab996d6", "type": "Gene", "text": [ "GJB2" ], "offsets": [ [ 217, 221 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fcfa0b1e-38a7-44e4-8fbe-791aef9a8f1a", "type": "Gene", "text": [ "GJB2" ], "offsets": [ [ 251, 255 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e1fa89f2-8ba9-4c15-a19b-a9adb85c0fac", "type": "Gene", "text": [ "GJB2" ], "offsets": [ [ 538, 542 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "114f0792-0d5a-49b8-b0f6-6b737507fe3b", "type": "Gene", "text": [ "GJB2" ], "offsets": [ [ 739, 743 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "12f2f261-7c63-477e-9da0-6c782297e64a", "type": "Gene", "text": [ "GJB2" ], "offsets": [ [ 1663, 1667 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "afcf1586-0caf-40f8-941d-926dd1bba11a", "type": "title", "text": [ "Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF: a family based association study." ], "offsets": [ [ 0, 138 ] ] }, { "id": "98ff9e67-2455-44f6-aa2e-6d46707b431a", "type": "abstract", "text": [ "Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia." ], "offsets": [ [ 139, 1836 ] ] } ]

[ { "id": "3a04ce10-c4f0-4925-9b9b-e529299d4f3d", "type": "Gene", "text": [ "HT2A" ], "offsets": [ [ 62, 66 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7b0c88b1-bfd8-4e5b-8d08-e26f50d593ac", "type": "Gene", "text": [ "DRD2" ], "offsets": [ [ 68, 72 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4c424130-3930-42e4-b759-40730ceb3824", "type": "Gene", "text": [ "DRD4" ], "offsets": [ [ 74, 78 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3377733c-8da7-4ddd-a7ef-ee1141373164", "type": "Gene", "text": [ "SLC6A3" ], "offsets": [ [ 80, 86 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "29b2a10f-a2b1-4a27-974f-3446e22fb5dc", "type": "Gene", "text": [ "DAT1" ], "offsets": [ [ 88, 92 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c7f9e459-5661-456e-9255-ab9e05ee5656", "type": "Gene", "text": [ "BDNF" ], "offsets": [ [ 99, 103 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9e65f905-9c24-4a57-993b-8e950be7cf9c", "type": "Gene", "text": [ "serotonin 2A receptor" ], "offsets": [ [ 561, 582 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3f0d8946-b483-4118-8624-3e3b0170c028", "type": "Gene", "text": [ "HT2A" ], "offsets": [ [ 584, 588 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "08c484e5-65a6-4289-bbea-ae30e4c34117", "type": "Gene", "text": [ "dopamine receptor types 2 and 4" ], "offsets": [ [ 591, 622 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2f8a013e-ec3f-472b-8fce-549e394a9fbf", "type": "Gene", "text": [ "dopamine transporter" ], "offsets": [ [ 624, 644 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9a4dc39b-67cb-430d-a919-9c7170c10e67", "type": "Gene", "text": [ "SLC6A3" ], "offsets": [ [ 646, 652 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c1a78c89-79aa-437d-ab03-e39daa8d41ea", "type": "Gene", "text": [ "brain-derived neurotrophic factor" ], "offsets": [ [ 659, 692 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f3900e49-5368-4193-98be-c83bddf7f403", "type": "Gene", "text": [ "BDNF" ], "offsets": [ [ 694, 698 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "394c260e-e3ed-4a70-b4c7-10e110df8bda", "type": "Gene", "text": [ "HT2A" ], "offsets": [ [ 1358, 1362 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a9dda996-bd0f-4e97-bfec-73e5dc276796", "type": "Gene", "text": [ "BDNF" ], "offsets": [ [ 1419, 1423 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fd3b164d-94a6-48f5-bcfe-98831eb971fe", "type": "Gene", "text": [ "SLC6A3" ], "offsets": [ [ 1483, 1489 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3f647b48-0d2a-46e7-ab27-5e15802ef308", "type": "Gene", "text": [ "DAT1" ], "offsets": [ [ 1493, 1497 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "1ee6dbd8-a1d2-4120-8c28-2334a9ec71f1", "type": "title", "text": [ "Genomic evidence for recent positive selection at the human MDR1 gene locus." ], "offsets": [ [ 0, 76 ] ] }, { "id": "283de6e5-f897-46c4-9587-4bd75351d8c5", "type": "abstract", "text": [ "The MDR1 multidrug transporter regulates the traffic of drugs, peptides and xenobiotics into the body as well as sensitive tissues like the brain, germ cells and the developing fetus. Hence, it may influence an individual's response to drugs as well as his/her susceptibility to complex diseases in which environmental factors, especially xenobiotics, play a role. Polymorphisms within this gene, especially single-nucleotide polymorphism e26/3435(C/T), have been variously associated with differences in MDR1 expression, function, drug response and disease susceptibility. Here, we report the detailed characterization of the haplotype and linkage disequilibrium architecture of the entire 200 kb of the MDR1 gene in five world populations, namely, Chinese, Malays, Indians, Caucasians and African-Americans. We observed varied haplotype diversity across the entire gene in the different populations. The major haplotype mh5, which contains the subhaplotype e12/1236T-e21/2677T-e26/3435T, is highly represented among the four non-African populations, while mh7, which contains the subhaplotype e12/1236C-e21/2677G-e26/3435C, accounts for over a third of African-American chromosomes. These observations are inconsistent with a simple population evolution model, but instead are suggestive of recent historical events that have maintained such long range linkage disequilibrium. Using a modified long-range haplotype test, we found statistically significant evidence of recent positive selection for the e21/2677T and e26/3435T alleles in the Chinese population, and for the e26/3435T allele in the Malay population. Interestingly, we also detected evidence for positive selection of the alternative allele e26/3435C in the African-American population. These data suggest that independent mutational events may have occurred on the mh5 and mh7 haplotypes of the MDR1 gene to confer positive selection in the non-African and African-American populations, respectively." ], "offsets": [ [ 77, 2049 ] ] } ]

[ { "id": "a2359ca5-4f17-4151-84e0-a898f06d6e45", "type": "Gene", "text": [ "MDR1" ], "offsets": [ [ 60, 64 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a39f3622-29d3-4161-b922-11215868c672", "type": "Gene", "text": [ "MDR1" ], "offsets": [ [ 81, 85 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4aedc276-adbc-4e22-8081-76bdf2e884ec", "type": "Gene", "text": [ "MDR1" ], "offsets": [ [ 587, 591 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a6953fed-f47b-430c-aeef-4d4a01a24780", "type": "Gene", "text": [ "MDR1" ], "offsets": [ [ 787, 791 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7e94d962-b526-4b2a-99e2-0431d2d9532a", "type": "Gene", "text": [ "MDR1" ], "offsets": [ [ 1944, 1948 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7f21f122-b478-4e1b-bc50-92530eb0b381", "type": "Gene", "text": [ "MDR1" ], "offsets": [ [ 1944, 1948 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c0c04381-1c7a-4f88-a188-2f73e6809894", "type": "title", "text": [ "Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia." ], "offsets": [ [ 0, 95 ] ] }, { "id": "a9ce43e7-12a4-4faa-80d5-c35416ff3d30", "type": "abstract", "text": [ "Proprotein convertase subtilisin/kexin type 9 (PCSK9) is at a locus for autosomal dominant hypercholesterolemia, and recent data indicate that the PCSK9 gene is involved in cholesterol biosynthesis. Mutations within this gene have previously been found to segregate with hypercholesterolemia. In this study, DNA sequencing of the 12 exons of the PCSK9 gene has been performed in 51 Norwegian subjects with a clinical diagnosis of familial hypercholesterolemia where mutations in the low-density lipoprotein receptor gene and mutation R3500Q in the apolipoprotein B-100 gene had been excluded. Two novel missense mutations were detected in the catalytic subdomain of the PCSK9 gene. Two patients were heterozygotes for D374Y, and one patient was a double heterozygote for D374Y and N157K. D374Y segregated with hypercholesterolemia in the two former families where family members were available for study. Our findings support the notion that mutations in the PCSK9 gene cause autosomal dominant hypercholesterolemia." ], "offsets": [ [ 96, 1112 ] ] } ]

[ { "id": "a71db557-4b60-4cd8-abaa-95f56da5101a", "type": "Gene", "text": [ "PCSK9" ], "offsets": [ [ 17, 22 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0cab83b9-e058-463c-9933-98a3cc589e1c", "type": "Gene", "text": [ "Proprotein convertase subtilisin/kexin type 9" ], "offsets": [ [ 96, 141 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "190d1c1f-f9fb-433c-a25f-352f92d8bf6e", "type": "Gene", "text": [ "PCSK9" ], "offsets": [ [ 143, 148 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c9629b30-335c-4588-b4b5-e51ce0ec96fd", "type": "Gene", "text": [ "PCSK9" ], "offsets": [ [ 243, 248 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "554013a7-01aa-49f8-97b3-6d6ffb394136", "type": "Gene", "text": [ "PCSK9" ], "offsets": [ [ 442, 447 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c9592b36-346e-48e2-9baa-1664bf278b3b", "type": "Gene", "text": [ "low-density lipoprotein receptor" ], "offsets": [ [ 579, 611 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4d8c3396-7336-4d1f-8e39-a17d823990ca", "type": "Gene", "text": [ "apolipoprotein B-100" ], "offsets": [ [ 644, 664 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e3fbc732-2b72-45da-bbb2-dbf9e3026f12", "type": "DomainMotif", "text": [ "catalytic" ], "offsets": [ [ 739, 748 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bac79ae7-395d-420c-b52c-d3a74910ae94", "type": "Gene", "text": [ "PCSK9" ], "offsets": [ [ 766, 771 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "128d0620-9173-4da5-be0c-d57f43091e5b", "type": "Gene", "text": [ "PCSK9" ], "offsets": [ [ 1055, 1060 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "bb0ac1d2-404e-4531-8fd5-5d1e88a2cf58", "type": "title", "text": [ "Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome." ], "offsets": [ [ 0, 108 ] ] }, { "id": "59d70c9c-7c60-4f2a-8525-151c96f9b250", "type": "abstract", "text": [ "3p deletion syndrome is a rare contiguous-gene disorder involving the loss of the telomeric portion of the short arm of chromosome 3 and characterized by developmental delay, growth retardation, and dysmorphic features. All reported cases have involved, at a minimum, the deletion of chromosome 3 telomeric to the band 3p25.3. Despite the presence of several genes in this region that are involved in neural development, a causative relationship between a particular transcript and the observed clinical manifestations has remained elusive. We have identified a child with characteristic physical features of 3p deletion syndrome and both verbal and nonverbal developmental delay who carries a de novo balanced translocation involving chromosomes 3 and 10. Fine mapping of this rearrangement demonstrates that the translocation breakpoint on chromosome 3 falls within the recently identified minimal candidate region for 3p deletion syndrome and disrupts the Contactin 4 (CNTN4) mRNA transcript at 3p26.2-3p26.3. This transcript (also known as BIG-2) is a member of the immunoglobulin super family of neuronal cell adhesion molecules involved in axon growth, guidance, and fasciculation in the central nervous system (CNS). Our results demonstrate the association of CNTN4 disruption with the 3p deletion syndrome phenotype and strongly suggest a causal relationship. These findings point to an important role for CNTN4 in normal and abnormal CNS development." ], "offsets": [ [ 109, 1568 ] ] } ]

[ { "id": "151f1aa3-75a4-48d2-a44f-25af873733f5", "type": "Gene", "text": [ "contactin 4" ], "offsets": [ [ 14, 25 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "894b9764-e9e1-4265-9758-424c6ccadbdf", "type": "Gene", "text": [ "CNTN4" ], "offsets": [ [ 27, 32 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c4b48b2e-d3b9-457c-af74-ca3b80b5ce17", "type": "Gene", "text": [ "Contactin 4" ], "offsets": [ [ 1068, 1079 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e11e664b-4e61-4eac-a535-f0335805ba1e", "type": "Gene", "text": [ "CNTN4" ], "offsets": [ [ 1081, 1086 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b151ebb1-ca29-4272-9288-06ff96c578a3", "type": "Gene", "text": [ "BIG-2" ], "offsets": [ [ 1153, 1158 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "244728a8-ded0-4870-87ca-5fcbb4489d08", "type": "FamilyName", "text": [ "immunoglobulin" ], "offsets": [ [ 1179, 1193 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "79d4da95-1776-40fc-a2c1-09d4c6277db4", "type": "Gene", "text": [ "CNTN4" ], "offsets": [ [ 1376, 1381 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4c74de41-ddbc-4dcf-85d6-c9800258ff62", "type": "Gene", "text": [ "CNTN4" ], "offsets": [ [ 1523, 1528 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "17ed319d-3e35-41e1-b4ee-c32ce0ca93ea", "type": "title", "text": [ "Offspring gender ratio and the rate of recurrent spontaneous miscarriages in jewish women at high risk for breast/ovarian cancer." ], "offsets": [ [ 0, 129 ] ] }, { "id": "2d1f0b73-423b-4bca-8fb8-bf92de804659", "type": "abstract", "text": [ "BRCA1/BRCA2 germline mutations are associated with an increased breast/ovarian cancer risk. Offspring gender ratios may be skewed against male births in BRCA1 mutation carriers. In addition, the lack of viable homozygous BRCA1/BRCA2-mutation carriers implies that recurrent miscarriages may be associated with homozygous fetuses. Jewish Israeli high-risk women who were tested for being carriers of the predominant BRCA1/BRCA2 mutations in Jewish high-risk families were analyzed for the sex of offspring and the rate of spontaneous miscarriages. Overall, 817 women participated: 393 BRCA1/BRCA2-mutation carriers (229 with breast/ovarian cancer) and 424 high-risk noncarriers (208 with breast/ovarian cancer). No differences between the male-to-female offspring ratios of all study groups were noted. Among mutation carriers, the offspring male-to-female ratio was 0.97 (444 : 460), and among mutation carriers with cancer it was 0.92 (262 : 284). Similarly, no offspring gender skewing was noted among high-risk noncarriers, regardless of health status. The rates of three or more spontaneous miscarriages among participants with at least one live birth were 4.37% (15/343) among mutation carriers and 3% (12/401) among high-risk women (P = not significant). In conclusion, the offspring gender ratio is similar in high-risk Jewish families and in the general population. The issue of the rate of recurrent miscarriages in high-risk Jewish women is unresolved." ], "offsets": [ [ 130, 1592 ] ] } ]

[ { "id": "d0b96984-31a5-4468-ac09-d0e0bc143751", "type": "Gene", "text": [ "BRCA1" ], "offsets": [ [ 130, 135 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "14365a93-7601-47ee-aa0a-1ca0732acfd1", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 136, 141 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "04a680ca-fc80-4768-b130-b0c6bfa0342c", "type": "Gene", "text": [ "BRCA1" ], "offsets": [ [ 283, 288 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "01c74881-29fe-46b8-8f7b-fa334a704bd8", "type": "Gene", "text": [ "BRCA1" ], "offsets": [ [ 351, 356 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5d8b9863-008b-4eb5-8276-e608993a7f4d", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 357, 362 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "badf18b3-f2aa-442a-a4e3-722fc7de3bfc", "type": "Gene", "text": [ "BRCA1" ], "offsets": [ [ 545, 550 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d2f706db-4926-4ab9-a8d7-5df3fe3baa82", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 551, 556 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "93e68b63-8ceb-4d2d-81af-9d1d0643a4e7", "type": "Gene", "text": [ "BRCA1" ], "offsets": [ [ 714, 719 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ba8c18ac-eb22-4464-8c25-7162b16eb9cc", "type": "Gene", "text": [ "BRCA2" ], "offsets": [ [ 720, 725 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "5aac8701-bc00-4473-86ce-21073fd2180e", "type": "title", "text": [ "Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids." ], "offsets": [ [ 0, 154 ] ] }, { "id": "77690bcb-0521-40f8-b208-d91f6803d95f", "type": "abstract", "text": [ "Corticosteroids mediate a variety of immunological actions and are commonly utilized in the treatment of a wide range of diseases. Unfortunately, therapy with this class of medications is associated with a large proportion of non-responders and significant side effects. Inhaled corticosteroids are the most commonly used asthma controller therapy. However, asthmatic response to corticosteroids also varies widely between individuals. We investigated the genetic contribution to the variation in response to inhaled corticosteroid therapy in asthma. The association of longitudinal change in lung function and single nucleotide polymorphisms from candidate genes crucial to the biologic actions of corticosteroids were evaluated in three independent asthmatic clinical trial populations utilizing inhaled corticosteroids as the primary therapy in at least one treatment arm. Variation in one gene, corticotropin-releasing hormone receptor 1 (CRHR1) was consistently associated with enhanced response to therapy in each of our three populations. Individuals homozygous for the variants of interest manifested a doubling to quadrupling of the lung function response to corticosteroids compared with lack of the variants (P-values ranging from 0.006 to 0.025 for our three asthmatic populations). As the primary receptor mediating the release of adrenocorticotropic hormone, which regulates endogenous cortisol levels, CRHR1 plays a pivotal, pleiotropic role in steroid biology. These data indicate that genetic variants in CRHR1 have pharmacogenetic effects influencing asthmatic response to corticosteroids, provide a rationale for predicting therapeutic response in asthma and other corticosteroid-treated diseases, and suggests this gene pathway as a potential novel therapeutic target." ], "offsets": [ [ 155, 1943 ] ] } ]

[ { "id": "b2f6c05d-c0b9-42c4-848e-0231e17057a3", "type": "Gene", "text": [ "CRHR1" ], "offsets": [ [ 69, 74 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4047c9e4-86be-4146-b54e-7acce1db340b", "type": "Gene", "text": [ "corticotropin-releasing hormone receptor 1" ], "offsets": [ [ 1054, 1096 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5df90131-3067-44e8-925a-d35dbdcba68b", "type": "Gene", "text": [ "CRHR1" ], "offsets": [ [ 1098, 1103 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "35650e69-0dd5-44b9-8481-ee52b1616b68", "type": "Gene", "text": [ "adrenocorticotropic hormone" ], "offsets": [ [ 1499, 1526 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1b597cbb-7720-4075-9370-af04c5bec1b7", "type": "Gene", "text": [ "CRHR1" ], "offsets": [ [ 1572, 1577 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ff4a0cc6-8250-4f9c-a5be-ead467fec52d", "type": "Gene", "text": [ "CRHR1" ], "offsets": [ [ 1677, 1682 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "353a8327-df10-4a67-af41-d260c596eff8", "type": "title", "text": [ "A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf-Hirschhorn syndrome." ], "offsets": [ [ 0, 123 ] ] }, { "id": "7fc7978e-acf5-4b91-a72b-00707d4dc93f", "type": "abstract", "text": [ "A total of five Wolf-Hirschhorn syndrome (WHS) patient with a 4p16.3 de novo microdeletion was referred because of genotype-phenotype inconsistencies, first explained as phenotypic variability of the WHS. The actual deletion size was found to be about 12 Mb in three patients, 5 Mb in another one and 20 Mb in the last one, leading us to hypothesize the presence of an extrachromosome segment on the deleted 4p. A der(4)(4qter --> p16.1::8p23 --> pter) chromosome, resulting from an unbalanced de novo translocation was, in fact, detected in four patients and a der(4)(4qter --> q32::4p15.3 --> qter) in the last. Unbalanced t(4;8) translocations were maternal in origin, the rec(4p;4q) was paternal. With the purpose of verifying frequency and specificity of this phenomenon, we investigated yet another group of 20 WHS patients with de novo large deletions (n = 13) or microdeletions (n = 7) and with apparently straightforward genotype-phenotype correlations. The rearrangement was paternal in origin, and occurred as a single anomaly in 19 out of 20 patients. In the remaining patient, the deleted chromosome 4 was maternally derived and consisted of a der(4)(4qter --> 4p16.3::8p23 --> 8pter). In conclusions, we observed that 20% (5/25) of de novo WHS-associated rearrangements were maternal in origin and 80% (20/25) were paternal. All the maternally derived rearrangements were de novo unbalanced t(4;8) translocations and showed specific clinical phenotypes. Paternally derived rearrangements were usually isolated deletions. It can be inferred that a double, cryptic chromosome imbalance is an important factor for phenotypic variability in WHS. It acts either by masking the actual deletion size or by doubling a quantitative change of the genome." ], "offsets": [ [ 124, 1900 ] ] } ]

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[ { "id": "9fe58283-ea5e-4384-b782-6fb72a49cdcf", "type": "title", "text": [ "Paraoxonase 1 polymorphisms and survival." ], "offsets": [ [ 0, 41 ] ] }, { "id": "baaf42d8-6e81-459b-89db-fbbb2f2315c0", "type": "abstract", "text": [ "The antioxidant enzyme paraoxonase 1 (PON1) has previously been suggested to confer protection against coronary heart disease (CHD), one of the main causes of death in the Western world. Two coding polymorphisms, 55M/L and 192Q/R, and a promoter variant, -107C/T, has been extensively studied with respect to susceptibility to CHD. In this study, we have investigated the impact of these three polymorphisms on mortality using a sample of 1932 Danish individuals aged 47-93 years, previously used in gene-longevity studies. A cross-sectional study comparing the genotype distribution of the three polymorphisms separately as well as the haplotype distribution in different age groups did not reveal any difference. However, a longitudinal follow-up study on survival in the same sample indicated that 192RR homozygotes have a poorer survival compared to QQ homozygotes (hazard rate: 1.38, P = 0.04). We hereafter used an independent sample of 541 Danish individuals from the oldest cohort and confirmed the initial findings (hazard rate: 1.38, P = 0.09). In both samples, the effect was most pronounced in women. Using self-reported data on ischemic heart disease to evaluate the impact of the PON 192Q/R polymorphism on susceptibility to CHD, we found only a nonsignificant trend of 192RR homozygosity in women being a risk factor. Our results thus indicates that PON1 192RR homozygosity is associated with increased mortality in women in the second half of life and that this increased mortality is possibly related to CHD severity and survival after CHD rather than susceptibility to development of CHD." ], "offsets": [ [ 42, 1648 ] ] } ]

[ { "id": "e830c363-958d-42af-b7ae-ced13d46d995", "type": "Gene", "text": [ "Paraoxonase 1" ], "offsets": [ [ 0, 13 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9ac37039-d5d3-46cb-9aec-dc933b07cea7", "type": "Gene", "text": [ "paraoxonase 1" ], "offsets": [ [ 65, 78 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2903428c-73b3-49f9-8e92-8806f67a4e7f", "type": "Gene", "text": [ "PON1" ], "offsets": [ [ 80, 84 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e2b6efcb-d1b7-4ccd-8f9b-7ec4913197ca", "type": "Gene", "text": [ "PON" ], "offsets": [ [ 1236, 1239 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c9dd6646-ce3b-4e5d-966f-1f2c948ceeb9", "type": "Gene", "text": [ "PON1" ], "offsets": [ [ 1407, 1411 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "1d6b0adb-19af-4df3-b8dd-79724f62d943", "type": "title", "text": [ "Trisomy 1 in a case of a missed abortion." ], "offsets": [ [ 0, 41 ] ] }, { "id": "19f7b1c5-44e5-4ae9-9c09-069757b559de", "type": "abstract", "text": [ "Most chromosomal trisomies lead to miscarriages. In all trisomies, trisomy 1 is the most rare case. We herein present a patient who demonstrated a gestational sac and a yolk sac on transvaginal ultrasound. However, at 53 days of gestation, the pregnancy was lost with a diagnosis of a blighted ovum. A D_C was recommended and performed. A cytogenetic analysis from chorionic villi demonstrated a 47,XX,+1 chromosome complement in all 100 cells. Regarding full trisomy 1, there has only been one case report of a preembryo and two case reports in a clinically recognized pregnancy to date." ], "offsets": [ [ 42, 630 ] ] } ]

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[ { "id": "9165601d-3fa2-4af8-93b7-d71a050472ae", "type": "title", "text": [ "CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations." ], "offsets": [ [ 0, 153 ] ] }, { "id": "5aeac667-ef69-4918-a934-49af882a65ea", "type": "abstract", "text": [ "PURPOSE: We reviewed CFTR mutation distribution among Hispanic and African American individuals referred for CF carrier screening and compared mutation frequencies to those derived from CF patient samples. METHODS: Results from CFTR mutation analyses received from January 2001 through September 2003, were analyzed for four populations: Hispanic individuals with a CF diagnosis (n = 159) or carrier screening indication (n = 15,333) and African American individuals with a CF diagnosis (n = 108) or carrier screening indication (n = 8,973). All samples were tested for the same 87 mutation panel. RESULTS: In the Hispanic population, 42 mutations were identified: 30 in the patient population (77.5% detection rate) and 33 among carrier screening referrals. Five mutations not included in the ACMG/ACOG carrier screening panel (3876delA, W1089X, R1066C, S549N, 1949del84) accounted for 7.55% detection in patients and 5.58% among carriers. Among African American referrals, 33 different mutations were identified: 21 in the patient population (74.4% detection) and 23 in the carrier screening population. Together, A559T and 711+5G>A were observed at a detection rate of 3.71% in CF patients and 6.38% in carriers. The mutation distribution seen in both the carrier screening populations reflected an increased frequency of mutations with variable expression such as D1152H, R117H, and L206W. CONCLUSIONS: A detailed analysis of CFTR mutation distribution in the Hispanic and African American patient and carrier screening populations demonstrates that a diverse group of mutations is most appropriate for diagnostic and carrier screening in these populations. To best serve the increasingly diverse U.S. population, ethnic-specific mutations should be included in mutation panels." ], "offsets": [ [ 154, 1939 ] ] } ]

[ { "id": "089b3973-16e2-4e24-9133-cc2dd025b2da", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 0, 4 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "96a90502-431d-4fa2-b003-0eb11c74ba21", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 175, 179 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a474f367-c709-41c7-93b0-3a5c6e2d5b8e", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 382, 386 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bcda9dae-14c8-40e3-9017-08ce3b6781f0", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 1587, 1591 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "3e430490-2cae-4466-aea9-c6d888057e0c", "type": "title", "text": [ "Fine mapping and identification of a candidate gene SSH1 in disseminated superficial actinic porokeratosis." ], "offsets": [ [ 0, 107 ] ] }, { "id": "40e7a76a-7fc1-4370-a2c4-3917fae2685c", "type": "abstract", "text": [ "Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, the genetic basis and pathogenesis of this disorder have not been elucidated yet. In this study, we performed a genome-wide linkage analysis in three Chinese affected families and localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on chromosome 12. Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family, and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role in actin dynamics. Our data suggested that cytoskeleton disorganization in epidermal cells is likely associated with the pathogenesis of DSAP." ], "offsets": [ [ 108, 1178 ] ] } ]

[ { "id": "c0b476af-d2fd-4df8-870c-1f8a0f797372", "type": "Gene", "text": [ "SSH1" ], "offsets": [ [ 52, 56 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5264241b-89b0-4cd5-a336-448168f42eda", "type": "Gene", "text": [ "SSH1" ], "offsets": [ [ 748, 752 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "144b37d5-5eea-451d-902f-f565fba27f4a", "type": "Gene", "text": [ "SSH1" ], "offsets": [ [ 848, 852 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ceb65f8b-94d7-4ce3-90d2-0027bb52cf5a", "type": "Gene", "text": [ "SSH1" ], "offsets": [ [ 983, 987 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "2233255f-d570-435f-90e0-eb3d5fa3a526", "type": "title", "text": [ "Alternative splicing in the N-terminus of Alzheimer's presenilin 1." ], "offsets": [ [ 0, 72 ] ] }, { "id": "e16902ee-b056-4c6e-b156-177a92b6b2cf", "type": "abstract", "text": [ "Presenilin 1 (PS1) is mutated in the majority of familial cases of Alzheimer disease (AD). Although it is clear that PS1 is involved in the processing of the amyloid precursor protein (APP), the exact function of PS1 is still elusive. Human presenilin 1 (PS1) is alternatively spliced, resulting in the presence or absence of a four-amino acid motif, VRSQ, in the PS1 N-terminus. In human tissues, both isoforms are expressed. Here we report that mouse and rat only express the longer PS1 isoform. The presence of this motif introduces a potential phosphorylation site for protein kinase C. Because the splice occurs in the region of PS1 that we have previously shown to bind to rabGDI, this might provide a regulatory mechanism for this interaction. Our data show that the -VRSQ isoform binds rabGDI, but the +VRSQ does not. Moreover, mutation of the putatively phosphorylated threonine in PS1 disrupts the binding to rabGDI, showing its importance for the interaction. To our knowledge this is the first study showing a functional difference between PS1 splice variants. The possible consequences for APP processing and the pathogenesis of AD are discussed." ], "offsets": [ [ 73, 1232 ] ] } ]

[ { "id": "60db7851-2a60-49b5-9f77-938507386a3d", "type": "Gene", "text": [ "presenilin 1" ], "offsets": [ [ 59, 71 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f91755e2-13a9-4d5a-b41d-27e4d3f03782", "type": "Gene", "text": [ "Presenilin 1" ], "offsets": [ [ 73, 85 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "23501194-bfed-4bb5-86f6-e4eebc7db612", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 87, 90 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4cfe6172-db8f-414a-a828-765ca3ac319e", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 190, 193 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "61713152-82fb-4a72-8aa6-b5239b78677f", "type": "FamilyName", "text": [ "amyloid precursor protein" ], "offsets": [ [ 231, 256 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b43787a5-01d0-4894-a8d1-9172246b2100", "type": "FamilyName", "text": [ "APP" ], "offsets": [ [ 258, 261 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3d2c92a5-560a-4b0c-b895-c1a658736536", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 286, 289 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8a735655-cc08-4619-ad7f-97e3772aea95", "type": "Gene", "text": [ "presenilin 1" ], "offsets": [ [ 314, 326 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e60d6b1c-0cc1-4f24-8c88-a60608ae4507", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 328, 331 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5ff83b88-3b38-4bb1-82d8-8a2d35542fca", "type": "DomainMotif", "text": [ "VRSQ" ], "offsets": [ [ 424, 428 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "43400ace-b38a-47c9-9003-45855bf606e9", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 437, 440 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "95320bfa-4965-451e-8af4-ec66341e155f", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 558, 561 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "462d11a1-b380-4136-a5b2-029d83b4e694", "type": "FamilyName", "text": [ "protein kinase C" ], "offsets": [ [ 646, 662 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d03e8299-a7c5-4eec-b300-c3ff17dcd5ea", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 707, 710 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b2ffd4fc-4dcf-42f6-aa7e-df4dd12a0d93", "type": "FamilyName", "text": [ "rabGDI" ], "offsets": [ [ 752, 758 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eac93dea-a26b-492b-be4a-d3c11752daed", "type": "DomainMotif", "text": [ "VRSQ" ], "offsets": [ [ 848, 852 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "00c0fcb0-c4d1-4bc1-802b-d407e0c93597", "type": "FamilyName", "text": [ "rabGDI" ], "offsets": [ [ 867, 873 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cdb783df-b70c-40ce-9900-0e0ccc3d1ba5", "type": "DomainMotif", "text": [ "VRSQ" ], "offsets": [ [ 884, 888 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5be63275-9a02-4c86-a61f-7cb05d12c5b7", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 964, 967 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bc15ff26-44de-4935-bf06-837c0a44bc93", "type": "FamilyName", "text": [ "rabGDI" ], "offsets": [ [ 992, 998 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1b5eb195-905b-484c-a2f9-45dbc892accf", "type": "Gene", "text": [ "PS1" ], "offsets": [ [ 1125, 1128 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9195689d-3ba8-41d0-b561-e5c13253a1f5", "type": "FamilyName", "text": [ "APP" ], "offsets": [ [ 1176, 1179 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "9e53545b-afcd-4b60-8a1d-8d78fc4f674b", "type": "title", "text": [ "Haplotype structure of the beta adrenergic receptor genes in US Caucasians and African Americans." ], "offsets": [ [ 0, 97 ] ] }, { "id": "66698400-49a0-4b76-96b5-9b469128be88", "type": "abstract", "text": [ "The beta-adrenergic receptors (beta-AR) are G protein-coupled receptors activated by epinephrine and norepinephrine and are involved in a variety of their physiological functions. Previously, three beta-AR genes (ADRB1, ADRB2 and ADRB3) were resequenced, identifying polymorphisms that were used in genetic association studies of cardiovascular and metabolic disorders. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: ADRB1 Arg389Gly and Gly49Ser, ADRB2 Arg16Gly and Gln27Glu, and ADRB3 Arg64Trp provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for each beta-AR gene that included the known functional markers and also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 27 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations and for each gene, a single block with little evidence of historical recombination was observed. For each gene, haplotype captured most of the information content of each functional locus, even if that locus was not genotyped, and presumably haplotype would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using beta-AR gene haplotype maps and marker panels as tools for linkage studies on beta-AR function." ], "offsets": [ [ 98, 1574 ] ] } ]

[ { "id": "9c7a26ad-5495-433a-a2be-64362157b120", "type": "FamilyName", "text": [ "beta adrenergic receptor" ], "offsets": [ [ 27, 51 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "96c237a5-0872-460b-90e3-bd367be34612", "type": "FamilyName", "text": [ "beta-adrenergic receptors" ], "offsets": [ [ 102, 127 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "689c7cb8-9f09-4340-96f0-61b233a9e690", "type": "FamilyName", "text": [ "beta-AR" ], "offsets": [ [ 129, 136 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f98af976-acd2-4157-ab37-ab372b9b9393", "type": "FamilyName", "text": [ "G protein-coupled receptors" ], "offsets": [ [ 142, 169 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c8953d4d-b4fc-4bc0-ab59-3913d4ccd58f", "type": "FamilyName", "text": [ "beta-AR" ], "offsets": [ [ 296, 303 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6a4c510f-64b7-41bc-af8d-686647e8d906", "type": "Gene", "text": [ "ADRB1" ], "offsets": [ [ 311, 316 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8315f970-bc9b-4e18-b6c3-5b382e88acce", "type": "Gene", "text": [ "ADRB2" ], "offsets": [ [ 318, 323 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a25d79e9-c03c-466e-97db-87e4db96b199", "type": "Gene", "text": [ "ADRB3" ], "offsets": [ [ 328, 333 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0568c2ae-6769-44a1-a32b-e4f2c04bfcd0", "type": "Gene", "text": [ "ADRB1" ], "offsets": [ [ 584, 589 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "40d20621-928e-48ab-a8bb-820706a071e1", "type": "Gene", "text": [ "ADRB2" ], "offsets": [ [ 614, 619 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6865a428-133b-450a-9c2b-9ceed701f3d5", "type": "Gene", "text": [ "ADRB3" ], "offsets": [ [ 647, 652 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "914f2da9-d993-410d-9245-542d004da6b9", "type": "FamilyName", "text": [ "beta-AR" ], "offsets": [ [ 788, 795 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8aae6996-5df7-4354-ba3a-e4949dc314b5", "type": "FamilyName", "text": [ "beta-AR" ], "offsets": [ [ 1479, 1486 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fc9dc3aa-b85f-48ef-aab3-6c86b485df2f", "type": "FamilyName", "text": [ "beta-AR" ], "offsets": [ [ 1557, 1564 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "096bbdaa-1f63-44d2-a981-79679dc164e4", "type": "title", "text": [ "Cis-acting transmission of genomic instability." ], "offsets": [ [ 0, 47 ] ] }, { "id": "d6bb7a20-1bbc-474b-8b25-c338954c6e69", "type": "abstract", "text": [ "Genomic instability is a highly pleiotropic phenotype, which may reflect a variety of underlying mechanisms. Destabilization has been shown in some cases to involve mutational alteration or inactivation of trans-acting cellular factors, for example, p53 or mismatch repair functions. However, aspects of instability are not well explained by mutational inactivation of trans-acting factors, and other epigenetic and cis-acting mechanisms have recently been proposed. The trans and cis models result in divergent predictions for the distribution of instability-associated genetic alterations within the genome, and for the inheritance of genomic instability among sibling sub-clones of unstable parents. These predictions have been tested in this study primarily by tracking the karyotypic distribution of chromosomal rearrangements in clones and sub-clones exhibiting radiation-induced genomic instability; inheritance of mutator phenotypes was also analyzed. The results indicate that genomic instability is unevenly transmitted to sibling sub-clones, that chromosomal rearrangements within unstable clones are non-randomly distributed throughout the karyotype, and that the majority of chromosomal rearrangements associated with instability affect trisomic chromosomal segments. Observations of instability in trisomic regions suggests that in addition to promoting further alterations in chromosomal number, aneuploidy can affect the recovery of structural rearrangements. In summary, these findings cannot be fully explained by invoking a homogeneously distributed factor acting in trans, but do provide support for previous suggestions that genomic instability may in part be driven by a cis-acting mechanism." ], "offsets": [ [ 48, 1762 ] ] } ]

[ { "id": "93b9beb6-05d0-40e6-a8d5-b40c205dd570", "type": "FamilyName", "text": [ "trans-acting cellular factors" ], "offsets": [ [ 254, 283 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5cefe8de-7c1c-412c-ade9-169fbd7caccb", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 298, 301 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "320f0e2b-bf8f-4a5f-b841-7e870fcec540", "type": "FamilyName", "text": [ "trans-acting factors" ], "offsets": [ [ 417, 437 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "13816048-30ea-4693-9b51-e055a9e6a333", "type": "title", "text": [ "Tumor associated antigen recognition by autologous serum in patients with breast cancer." ], "offsets": [ [ 0, 88 ] ] }, { "id": "cff137bd-ed5c-4b2a-8a4f-c40bac1e6136", "type": "abstract", "text": [ "Breast cancer accounts for 30-40% of all deaths from cancers in females. In an effort to identify tumor associated antigens that may be useful for immunotherapy, we utilized serological analysis of recombinant cDNA expression libraries (SEREX) technique to identify breast cancer-associated antigens. SEREX screening of cDNA expression libraries derived from 3 breast cancer patients identified a total of 88 positive clones (bcg-1 to bcg-88), including 27 hitherto unknown sequences. The cDNA sequences and mRNA expression patterns were characterized. Seroreactivity of the SEREX clones were determined in sera from 75 breast cancer patients, 75 colon cancer patients, and 25 healthy donors. Expression analysis on a cDNA panel from 17 different normal tissues by reverse transcription-PCR (RT-PCR) revealed tissue restricted mRNA expression of 2 of the 27 unknown antigens. Bcg-72 is expressed only in breast, prostate and thymus, while bcg-84 is expressed at moderate levels in testis, spleen and breast. The other 25 unknown antigens were expressed in most other tissues. Serologic assay revealed that 7 out of the 88 clones showed reactivity to at least one serum from either 75 breast or 75 colon cancer patients. These clones did not react with sera from a panel of 25 healthy adult individuals. Our results demonstrate the utility of the SEREX approach for the identification of potential tumor associated antigens in human breast cancer." ], "offsets": [ [ 89, 1535 ] ] } ]

[ { "id": "39dfa60b-d49d-4196-9e80-60b81dc15b0c", "type": "Gene", "text": [ "bcg-1" ], "offsets": [ [ 515, 520 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "125a4ef9-1c94-46d2-aba4-7ebb4f50adac", "type": "title", "text": [ "Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy." ], "offsets": [ [ 0, 143 ] ] }, { "id": "0143b086-0991-44ef-b357-b61eac413001", "type": "abstract", "text": [ "INTRODUCTION: Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). BM is a relatively mild dominantly inherited disorder with proximal weakness and distal joint contractures. UCMD is an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. METHODS: We developed a method for rapid direct sequence analysis of all 107 coding exons of the COL6 genes using single condition amplification/internal primer (SCAIP) sequencing. We have sequenced all three COL6 genes from genomic DNA in 79 patients with UCMD or BM. RESULTS: We found putative mutations in one of the COL6 genes in 62% of patients. This more than doubles the number of identified COL6 mutations. Most of these changes are consistent with straightforward autosomal dominant or recessive inheritance. However, some patients showed changes in more than one of the COL6 genes, and our results suggest that some UCMD patients may have dominantly acting mutations rather than recessive disease. DISCUSSION: Our findings may explain some or all of the cases of UCMD that are unlinked to the COL6 loci under a recessive model. The large number of single nucleotide polymorphisms which we generated in the course of this work may be of importance in determining the major phenotypic variability seen in this group of disorders." ], "offsets": [ [ 144, 1583 ] ] } ]

[ { "id": "0d221903-7a5e-441d-8467-59e9e273b924", "type": "FamilyName", "text": [ "collagen VI" ], "offsets": [ [ 49, 60 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ab6cb78f-b278-4977-b031-fb5fb449dc11", "type": "FamilyName", "text": [ "collagen VI" ], "offsets": [ [ 190, 201 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c5f874c2-0f4f-4b35-a512-5aa8f611cfe3", "type": "Gene", "text": [ "COL6A1" ], "offsets": [ [ 203, 209 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8a45ac2-d31c-4f90-8ca9-64161550b00d", "type": "Gene", "text": [ "COL6A2" ], "offsets": [ [ 211, 217 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "07d8177c-50cb-42ad-9f8e-9522f5b493ad", "type": "Gene", "text": [ "COL6A3" ], "offsets": [ [ 223, 229 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "211a29ce-2793-485a-9578-1fe124305665", "type": "FamilyName", "text": [ "COL6" ], "offsets": [ [ 643, 647 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d1449a3e-64c5-4ac3-ad50-42cd7c5ac232", "type": "FamilyName", "text": [ "COL6" ], "offsets": [ [ 755, 759 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "214f5f9b-1ddf-41a9-a4d3-7b06c835c367", "type": "FamilyName", "text": [ "COL6" ], "offsets": [ [ 866, 870 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "577e23f3-98f1-4ce3-bf2b-2294179c5813", "type": "FamilyName", "text": [ "COL6" ], "offsets": [ [ 945, 949 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b65e8766-7750-466c-aed4-70bfa257dbbd", "type": "FamilyName", "text": [ "COL6" ], "offsets": [ [ 1126, 1130 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b8f65317-5bad-4165-a90c-66b04bc46944", "type": "FamilyName", "text": [ "COL6" ], "offsets": [ [ 1349, 1353 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "d3be72ff-1575-4fd3-84f2-d274066c4abc", "type": "title", "text": [ "Photochemoprevention of ultraviolet B signaling and photocarcinogenesis." ], "offsets": [ [ 0, 72 ] ] }, { "id": "8c4d6b1a-9fd7-4612-b729-411e77409431", "type": "abstract", "text": [ "Exposure to solar radiation, particularly its ultraviolet (UV) B component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formation, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. Amongst these various adverse effects of UV radiation, skin cancer is of the greatest concern. Over the years, changes in lifestyle has led to a significant increase in the amount of UV radiation that people receive, and this consequently has led to a surge in the incidence of skin cancer. The development of skin cancer is a complex multistage phenomenon involving three distinct stages exemplified by initiation, promotion and progression stages. Each of these stages is mediated via alterations in various cellular, biochemical, and molecular changes. Initiation, the first step in the carcinogenesis process is essentially an irreversible step in which genetic alterations occur in genes that ultimately leads to DNA modification and fixation of mutation. Tumor promotion is the essential process in cancer development involving clonal expansion of initiated cells giving rise to pre-malignant and then to malignant lesions, essentially by alterations in signal transduction pathways. Tumor progression involves the conversion of pre-malignant and malignant lesions into an invasive and potentially metastatic malignant tumor. All these processes for skin cancer development involve stimulation of DNA synthesis, DNA damage and proliferation, inflammation, immunosuppression, epidermal hyperplasia, cell cycle dysregulation, depletion of antioxidant defenses, impairment of signal transduction pathways, induction of cyclooxygenase, increase in prostaglandin synthesis, and induction of ornithine decarboxylase. Photochemoprevention has been appreciated as a viable approach to reduce the occurrence of skin cancer and in recent years, the use of agents, especially botanical antioxidants, present in the common diet and beverages consumed by human population have gained considerable attention as photochemopreventive agents for human use. Many such agents have also found a place in skin care products. Although this is more common in oriental countries, its popularity is significantly growing in western countries. In this article, we have summarized the available information of laboratory studies on UVB-mediated signaling that can be exploited as targets for photochemoprevention. We suggest that the use of skin care products supplemented with proven chemopreventive agents in conjunction with the use of sunscreens along with educational efforts may be an effective strategy for reducing UV-induced photodamage and skin cancer in humans. The mechanistic basis for the use of such products is discussed." ], "offsets": [ [ 73, 2871 ] ] } ]

[ { "id": "01860412-1325-419e-b54e-5ff9200135fb", "type": "Gene", "text": [ "ornithine decarboxylase" ], "offsets": [ [ 1847, 1870 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c4433a12-e6de-464c-be92-ca50270c8420", "type": "title", "text": [ "Molecular genetic and ocular findings in patients with holt-oram syndrome." ], "offsets": [ [ 0, 74 ] ] }, { "id": "fc68ea2a-1b69-4503-9d74-d453337ec467", "type": "abstract", "text": [ "PURPOSE: The autosomal dominant Holt-Oram syndrome (HOS) is characterized by upper limb and cardiac septal defects. Mutations of the TBX5 gene have been identified as the underlying gene defect in HOS. Embryonic expression of TBX5 has been found in the human retina. This is the first report of ocular findings in two unrelated families with mutations in the TBX5 gene. METHODS: Six living persons affected with HOS and 10 unaffected family members were subjected to mutation analysis and complete ophthalmological examination, including electrophysiological examinations (EOG and flash ERG). RESULTS: A heterozygous single base-pain substitution in exon 5 (408C --> A) was detected in all affected patients. All examined affected patents were ophthalmological asymptomatic with normal EOG. A scotopic elongated b-wave latency was found in affected family members who were older than 35 years. The ERG was normal in the young patients. CONCLUSIONS: Haploinsufficiency of TBX5 alters the dorsal-ventral polarity in developing eye vesicles without amy detected functional loss in human. Slight ERG abnormalities later in life may be a result of changes induced by the inner ganglion cell layer in the inner nuclear layer." ], "offsets": [ [ 75, 1297 ] ] } ]

[ { "id": "9f787042-8991-47f7-a216-3fe36f77eee2", "type": "Gene", "text": [ "TBX5" ], "offsets": [ [ 208, 212 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f4b7f960-ca61-4309-95a2-9a69ac4c5aee", "type": "Gene", "text": [ "TBX5" ], "offsets": [ [ 301, 305 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "44ae3652-185d-4427-98b7-e7a47f402f05", "type": "Gene", "text": [ "TBX5" ], "offsets": [ [ 434, 438 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8e5f57b4-0b0f-4c06-9ef0-4b48023da7d6", "type": "Gene", "text": [ "TBX5" ], "offsets": [ [ 1049, 1053 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "3ebed2cf-c34d-4b79-aaba-3ec9178cc221", "type": "title", "text": [ "Low RET mutation frequency and polymorphism analysis of the RET and EDNRB genes in patients with Hirschsprung disease in Taiwan." ], "offsets": [ [ 0, 128 ] ] }, { "id": "93086d3a-d7c1-49d9-adb7-21ff0d695a51", "type": "abstract", "text": [ "Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a relatively common disorder characterized by the absence of ganglion cells in the nerve plexuses of the lower digestive tract, resulting in intestinal obstruction in neonates. Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. In this study, we collected genomic DNA samples from 55 HSCR patients in central Taiwan and analyzed the coding regions of the RET and EDNRB genes by PCR amplification and DNA sequencing. In the 55 patients, an A to G transition was detected in two (identical twin brothers). The mutation was at the end of RET exon 19 at codon 1062 (Y1062C), a reported critical site for the signaling pathways. Single nucleotide polymorphisms (SNP) in exons 2, 7, 11, 13, and 15 of RET and exon 4 of EDNRB in the HSCR patients or controls were detected. The differences between patients and controls in allele distribution of the five RET polymorphic sites were statistically significant. The most frequent genotype encompassing exons 2 and 13 SNPs (the polymorphic sites with the highest percentage of heterozygotes) was AA/GG in patients, which was different from the AG/GT in the normal controls. Transmission disequilibrium was observed in exons 2, 7, and 13, indicating nonrandom association of the susceptibility alleles with the disease in the patients. This study represents the first comprehensive genetic analysis of HSCR disease in Taiwan." ], "offsets": [ [ 129, 1672 ] ] } ]

[ { "id": "8a72ffad-5c6a-4430-aaa6-878d911edbe9", "type": "Gene", "text": [ "RET" ], "offsets": [ [ 4, 7 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "48103664-5051-4b17-b797-acf54dfc696b", "type": "Gene", "text": [ "RET" ], "offsets": [ [ 60, 63 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "42a29552-1bcb-48a9-b71e-ce90e1acf066", "type": "Gene", "text": [ "EDNRB" ], "offsets": [ [ 68, 73 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6f63c83b-9f9e-42bc-949e-9edc1149fc78", "type": "Gene", "text": [ "RET" ], "offsets": [ [ 404, 407 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "80a76999-0d98-4ec4-96c1-01011775d56a", "type": "Gene", "text": [ "receptor tyrosine kinase" ], "offsets": [ [ 408, 432 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cb4032b5-4808-4be9-8c7a-5b79d1cce1ab", "type": "Gene", "text": [ "endothelin receptor B" ], "offsets": [ [ 437, 458 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d5ea59ea-f936-4e08-812f-b359795c4956", "type": "Gene", "text": [ "EDNRB" ], "offsets": [ [ 460, 465 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2df4c2a6-c0a5-4d57-8a0f-36007bcd9316", "type": "Gene", "text": [ "RET" ], "offsets": [ [ 664, 667 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dace0ae8-90ae-4494-80cd-8bc32d016487", "type": "Gene", "text": [ "EDNRB" ], "offsets": [ [ 672, 677 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "896ec89d-ec1b-4769-9073-a3fbe6441e6f", "type": "Gene", "text": [ "RET" ], "offsets": [ [ 844, 847 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "37bc33b4-6f12-4e04-aeac-5b42197df116", "type": "Gene", "text": [ "RET" ], "offsets": [ [ 1004, 1007 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "05f6aaa2-c895-4a22-827e-822cf26f3a45", "type": "Gene", "text": [ "EDNRB" ], "offsets": [ [ 1022, 1027 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "abdb4af0-8855-4925-b6ab-bb9c09fe86e6", "type": "Gene", "text": [ "RET" ], "offsets": [ [ 1157, 1160 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "97e4d6db-b05b-47a7-94f7-4eefe5f480b8", "type": "title", "text": [ "Superimposing polymorphism: the case of a point mutation within a polymorphic Alu insertion." ], "offsets": [ [ 0, 92 ] ] }, { "id": "a2f126f1-1f52-4949-bd84-7270691b640f", "type": "abstract", "text": [ "The COL3A1 Alu insertion is a member of the AluY subfamily. It has been found to be absent in non-human primates and polymorphic in worldwide human populations. The integration of the element into the human genome seems to have preceded the initial migration(s) of anatomically modern humans out of the African continent. Although the insertion has been detected in populations from all the continents, its highest frequency values are located within sub-Saharan Africa. The sequence alignment of the COL3A1 insertion from several African individuals revealed a bi-allelic single nucleotide polymorphism (SNP) at the downstream terminus of the element's poly-A tract. Once discovered, a selective PCR procedure was designed to determine the frequency of both alleles in 19 worldwide populations. The A-allele in this binary SNP experiences a clinal increase in the eastward direction from Africa to Southeast Asia and Mongolia, reaching fixation in the two latter regions. The T variant, on the other hand, exhibits a westward clinal increase outside of Africa, with its lowest frequency in Asia and achieving fixation in northern Europe. The presence of this internal SNP extends the usefulness provided by the polymorphic Alu insertion (PAI). It is possible that superimposing polymorphisms like this one found in the COL3A1 locus may accentuate signals from genetic drift events allowing for visualization of recent dispersal patterns." ], "offsets": [ [ 93, 1536 ] ] } ]

[ { "id": "26d20025-143a-4267-952d-775931781849", "type": "Gene", "text": [ "COL3A1" ], "offsets": [ [ 97, 103 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7e6408e3-9bf6-4d6e-88ff-974da6b85a2c", "type": "FamilyName", "text": [ "AluY" ], "offsets": [ [ 137, 141 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8f2324c4-ea25-4127-9e8f-b1fd185f04bd", "type": "Gene", "text": [ "COL3A1" ], "offsets": [ [ 594, 600 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f1c78e04-1717-4d1d-a0b1-7476b29472f8", "type": "Gene", "text": [ "COL3A1" ], "offsets": [ [ 1418, 1424 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "ce80f99a-ee40-4b52-bacb-92f980f47056", "type": "title", "text": [ "Burkitt-type acute leukemia in a patient with B-prolymphocytic leukemia: evidence for a common origin." ], "offsets": [ [ 0, 102 ] ] }, { "id": "dd75798a-4c65-4938-9c35-26a50b875fc2", "type": "abstract", "text": [ "Burkitt-type acute leukemia cells were present in the bone marrow of a patient with B-prolymphocytic leukemia diagnosed from peripheral blood cell morphology. Immunophenotype analysis confirmed morphological patterns. Cytogenetic and fluorescence in situ hybridization (FISH) analysis showed an identical t(8;22)(q24;q21) with MYC locus rearrangement in blood and bone marrow cells, with additional chromosome abnormalities in the bone marrow. In addition, the loss of one copy of the TP53 gene and identical IGH DNA clonal rearrangements were shown with FISH and polymerase chain reaction analysis respectively in the two types of leukemic cells. These data indicated the common origin of the two coexisting leukemias and are the first example of such occurrence in a leukemic patient." ], "offsets": [ [ 103, 889 ] ] } ]

[ { "id": "d33147f1-385e-49ac-bc43-5aa4389ebc11", "type": "Gene", "text": [ "MYC" ], "offsets": [ [ 430, 433 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2e404285-9839-4d39-8387-5d32620749d1", "type": "Gene", "text": [ "TP53" ], "offsets": [ [ 588, 592 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8814848-7695-4f52-8048-75712b64b6b9", "type": "Gene", "text": [ "IGH" ], "offsets": [ [ 612, 615 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "20659cc9-5e94-4658-b6ef-caaa4dfefc66", "type": "title", "text": [ "Haplotypes of variants in the UDP-glucuronosyltransferase1A9 and 1A1 genes." ], "offsets": [ [ 0, 75 ] ] }, { "id": "d2ae1d92-0a14-4eed-a92c-f4958584d04d", "type": "abstract", "text": [ "OBJECTIVES: Nine different functional UGT1A enzymes are generated from a single UGT1A gene by alternative splicing, with each enzyme having a unique exon 1. SN-38, the active metabolite of the anticancer agent irinotecan, is metabolized by both UGT1A1 and UGT1A9. We aim to characterize the UGT1A9-UGT1A1 haplotypes in Asians and Caucasians and gain insights on their functional consequences. METHODS: Asian and Caucasian individuals were genotyped for UGT1A1 and UGT1A9 variants. RESULTS: A higher frequency of the UGT1A9 -118T10 allele was observed in Asians compared to Caucasians, while the -275T>A and -2152C>T variants were relatively uncommon in Caucasians and not found in Asians. The strongest linkage disequilibrium (LD) was observed between the UGT1A1 -53 and -3156 and between the UGT1A9 -275 and -2152 loci. Lower LD was observed between the -118 UGT1A9 variant and the UGT1A1 variants. Fourteen UGT1A9-UGT1A1 haplotypes were found in Asians, seven of them found to be shared by both populations. Common UGT1A9-UGT1A1 diplotypes were defined, and a difference was observed across the SN-38 glucuronidation rates in Caucasian livers stratified by diplotypes. CONCLUSION: This study for the first time described common UGT1A9-UGT1A1 haplotypes, highlighting important ethnic differences between Asians and Caucasians. If the functional effect of these haplotypes can be confirmed, this haplotypic information would be applicable to the correct design of prospective clinical studies of irinotecan, as well as of other drugs primarily metabolized by both UGT1A1 and UGT1A9." ], "offsets": [ [ 76, 1665 ] ] } ]

[ { "id": "4bfaeea7-438f-4935-987d-969887ddb1af", "type": "Gene", "text": [ "UDP-glucuronosyltransferase1A9 and 1A1" ], "offsets": [ [ 30, 68 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ac7b2817-c2ca-4eee-a0f0-2a51d6a8adf9", "type": "Gene", "text": [ "UGT1A" ], "offsets": [ [ 114, 119 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a537f414-1a09-4594-8d85-4232cf3d4771", "type": "Gene", "text": [ "UGT1A" ], "offsets": [ [ 156, 161 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "168ceb7b-44d1-4035-b04d-f8c6b65905eb", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 321, 327 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a1a82ff3-f09a-4174-b005-8fefc84533e4", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 332, 338 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4454c99f-da80-4981-aa80-e62bd4b94856", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 367, 373 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5accd88d-c4e1-4de8-95b8-a22e4fb4ae8e", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 374, 380 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b40090c7-be03-4102-9eb6-06ce6bdada5f", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 529, 535 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bf1b64bb-1a8d-4051-b39f-b6215d7c9978", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 540, 546 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6d9af0b8-3986-4718-9807-5c24d7a0bf30", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 592, 598 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "496fd57f-dd27-42db-b45c-4299af71cf4b", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 838, 844 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "377e822a-9b97-4c5e-b09c-effe75ecdcae", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 875, 881 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6860d24d-dba5-4815-a14b-e5ff8c8cedd5", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 942, 948 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2fe217ff-b14d-41fd-b863-9ef678a5ebea", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 965, 971 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1fc5c1d1-6e98-4d32-afaf-b0a00aac05ae", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 991, 997 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0f88a3f9-c942-422c-91db-67797a844140", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 998, 1004 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "50d63ec2-2c17-4e8c-b977-d1b5aee78860", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 1099, 1105 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b7847fa1-233e-4b11-b91d-abf6ec0648d2", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 1106, 1112 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "964114f3-4b7c-4a05-9fc5-b808cb6af34e", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 1312, 1318 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7aa9cdf9-6926-436f-a2a6-fde8e47c96b3", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 1319, 1325 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ffef7ef5-9813-40f7-a977-97c70b4ccd90", "type": "Gene", "text": [ "UGT1A1" ], "offsets": [ [ 1647, 1653 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a3c07e53-c306-4a3b-b865-fe1e9044f2ae", "type": "Gene", "text": [ "UGT1A9" ], "offsets": [ [ 1658, 1664 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "020ceac5-45b4-49e2-b8e3-764963d58a19", "type": "title", "text": [ "Identification of a transcriptionally active hVH-5 pseudogene on 10q22.2." ], "offsets": [ [ 0, 73 ] ] }, { "id": "5efb6a4b-f6ba-4067-9d89-83e565f86b9f", "type": "abstract", "text": [ "Mitogen-activated protein kinases (MAPKs) are important regulators of a vast number of biological functions that affect life and death of eukaryotic cells and are tightly regulated by the concerted action of several phosphatases. Among these is the human homologue of vaccinia virus H1 phosphatase gene clone 5 (hVH-5) product, which dephosphorylates and thus inhibits members of the MAPK family. Here, we analyzed hVH-5 transcripts in mammary carcinoma cell lines and discovered a sequence with 88% similarity to hVH-5 transcripts. Because this variant of hVH-5 lacked intronic sequences in its genomic structure, we suggest it might be a processed pseudogene of hVH-5. psihVH-5 transcripts were detected in human peripheral tissues as well as in 11 of 14 breast cancer cell lines. In respect to the normal hVH-5 gene, the pseudogene contains several point mutations and a frame shift due to the deletion of 2 bases that would lead to the truncation of the putative psihVH-5 product." ], "offsets": [ [ 74, 1058 ] ] } ]

[ { "id": "ca40e606-582b-41d8-90c0-4b53c97daa54", "type": "Gene", "text": [ "hVH-5" ], "offsets": [ [ 45, 50 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "732edec5-30e2-41b1-bb87-13fe96f17d82", "type": "FamilyName", "text": [ "Mitogen-activated protein kinases" ], "offsets": [ [ 74, 107 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c4f7d2e3-d4fe-4491-b3f8-94371af1c04d", "type": "FamilyName", "text": [ "MAPKs" ], "offsets": [ [ 109, 114 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "878e632f-a03e-4edc-82c7-27c0b3ef492d", "type": "Gene", "text": [ "vaccinia virus H1 phosphatase gene clone 5" ], "offsets": [ [ 342, 384 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a9b072d4-701c-415d-8012-73e0da0fa036", "type": "Gene", "text": [ "hVH-5" ], "offsets": [ [ 386, 391 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "29b34b91-e8a1-4898-bb77-2f99615a4a71", "type": "FamilyName", "text": [ "MAPK" ], "offsets": [ [ 458, 462 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "63d1f194-ab71-4454-8d2b-bc598448f742", "type": "Gene", "text": [ "hVH-5" ], "offsets": [ [ 489, 494 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "af16887f-62ce-4f99-8cfc-57b658241398", "type": "Gene", "text": [ "hVH-5" ], "offsets": [ [ 588, 593 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "87b8b45c-1ed3-4f22-b48b-44308a32872f", "type": "Gene", "text": [ "hVH-5" ], "offsets": [ [ 631, 636 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6914db1c-6d29-4952-8ef9-82e94911d1fe", "type": "Gene", "text": [ "hVH-5" ], "offsets": [ [ 738, 743 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "685dbe85-3642-482d-ba96-0ca753034c87", "type": "Gene", "text": [ "hVH-5" ], "offsets": [ [ 882, 887 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "3f8958a7-35bb-4f2e-a46c-b298df3b2735", "type": "title", "text": [ "Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells." ], "offsets": [ [ 0, 166 ] ] }, { "id": "842a582b-a9e3-4c32-86dd-37ced3824a23", "type": "abstract", "text": [ "OBJECTIVES: SLCO1B1*5 and SLCO1B1*15 have been reported to reduce the clearance of pravastatin in healthy volunteers. However, there remains controversy in the effects of SLCO1B1*5 on the activity of OATP1B1 in vitro. In addition, the effect of SLCO1B1*15 on the function of OATP1B1 has not been studied using cDNA-expression systems. Object of the present study was to study the influence of SLCO1B1*5, *15 and *15+C1007G, a novel haplotype found in a patient with pravastatin-induced myopathy, on the functional properties of OATP1B1 by transient expression systems of HEK293 and HeLa cells using endogenous conjugates and statins as substrates. METHODS: Transporting assays for endogenous substrates were performed using tritium labeled estradiol-17beta-D-glucuronide and estrone-3-sulfate. Quantitation of pravastatin, atorvastatin, cerivastatin and simvastatin were carried out using HPLC tandem mass spectrometry. RESULTS: The transporting activities of cells expressing SLCO1B1*5, *15 and *15+C1007G decreased significantly but those of SLCO1B1*1b, *1a+C1007G and *1b+C1007G were not altered for all of the substrates tested except for simvastatin. Kinetic analysis of pravastatin and atorvastatin showed that Km values were not altered but Vmax values decreased significantly in cells expressing SLCO1B1*5, *15 and *15+C1007G. Immunocytochemical study showed that SLCO1B1*5, *15 and *15+C1007G proteins are localized not only at the plasma membrane but also in the intracellular space. CONCLUSIONS: These findings suggest that 521T>C, existing commonly in SLCO1B1*5, *15 and *15+C1007G, is the key single nucleotide polymorphism (SNP) that determines the functional properties of SLCO1B1*5, *15 and *15+C1007G allelic proteins and that decreased activities of these variant proteins are mainly caused by a sorting error produced by this SNP." ], "offsets": [ [ 167, 2019 ] ] } ]

[ { "id": "e5937e2c-bbc3-46c2-8482-b8cd8c2af726", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 31, 38 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5122ddd7-91ab-44ff-af68-2cc8752f268c", "type": "Gene", "text": [ "OATP-C" ], "offsets": [ [ 40, 46 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "56446020-f055-4762-aea2-0d2280132336", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 58, 65 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c4841abf-d914-4c68-be92-dd14ceb1eefb", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 69, 76 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "272b640a-a8ff-4251-a056-57922e628cdf", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 84, 91 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "915a1d3a-380a-4051-bc9c-2eb61a228696", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 179, 186 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c2572cd8-6298-4272-a542-61f6b52b1a4b", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 193, 200 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "56654082-2676-4ad4-b612-46a11ea94b49", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 338, 345 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a49e5eb8-6564-44fd-83c6-9ebd8224319a", "type": "Gene", "text": [ "OATP1B1" ], "offsets": [ [ 367, 374 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8bf570f0-1710-4d7a-9d6f-e3580785a709", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 412, 419 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1d6b2f61-f9e7-4509-b921-9d4af2050255", "type": "Gene", "text": [ "OATP1B1" ], "offsets": [ [ 442, 449 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7a1f6000-f645-4022-aa03-07208e79216b", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 560, 567 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f3806e5c-fd15-4d24-b62b-a165d8edb9fc", "type": "Gene", "text": [ "OATP1B1" ], "offsets": [ [ 695, 702 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0b6f8205-c150-4e22-9465-017f01e03f83", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1144, 1151 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8551fcf-dee7-425c-9be0-9a6d22c02ea7", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1211, 1218 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dda72416-0aa6-4349-834a-3ff9b9b958c2", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1471, 1478 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c5e66a77-1e16-4a02-b2ae-088f678bf104", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1539, 1546 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8d8f2b0d-b2e5-446d-9eda-79a3783e69da", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1734, 1741 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7fe39d87-a01e-419c-aa5e-e76732230a93", "type": "Gene", "text": [ "SLCO1B1" ], "offsets": [ [ 1858, 1865 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "8e184aaf-400c-4396-85a5-ae465b782456", "type": "title", "text": [ "The effect of exogenous estradiol treatment on the mRNA expression of vascular endothelial growth factor and its receptors in cultured human oviduct mucosal cells." ], "offsets": [ [ 0, 163 ] ] }, { "id": "6bcd5b18-59a4-4c13-b54b-e23096e93af1", "type": "abstract", "text": [ "PURPOSE: To evaluate the responses of cultured oviduct mucosal cells to exogenous estradiol treatment in regulating the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors. METHODS: The mucosal layer of the ampullary regions of the human oviduct was isolated and cultured with (study groups) or without (control group) the addition of exogenous estradiol in five different concentrations. Semiquantitative reverse-transcriptase-polymerase chain reaction was performed on the oviduct mucosal cells before and after the 6-day culture. RESULTS: There were no significant differences in the mRNA expression of VEGF and its receptors, both KDR and flt-1, between the five study groups and the control group. CONCLUSIONS: The mRNA expression of VEGF and its receptors is not altered by exogenous estradiol treatment in cultured oviduct. This helps to explain the mechanism of temporal regulation of VEGF in human oviduct, which reaches the peak level in the peri-ovulatory stage when both the serum estradiol and gonadotropins concentrations are high." ], "offsets": [ [ 164, 1236 ] ] } ]

[ { "id": "cd97ec3a-9560-49c9-825b-32515743a2ae", "type": "Gene", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 70, 104 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6659b0a8-9b9a-45ab-9c1f-c8020ddbeba5", "type": "Gene", "text": [ "vascular endothelial growth factor" ], "offsets": [ [ 303, 337 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bb07a9a1-3f14-4e06-af03-f2436eca054b", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 339, 343 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9d595df6-9ecf-4b4e-bf27-8d38091e7fb5", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 797, 801 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cf0f73e5-f4d7-4ec8-b18c-c17dc0abdea0", "type": "Gene", "text": [ "KDR" ], "offsets": [ [ 826, 829 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f66766be-1575-4f57-a442-f708d954a033", "type": "Gene", "text": [ "flt-1" ], "offsets": [ [ 834, 839 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "75491926-6bee-4704-bfa8-6cffc3711804", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 930, 934 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "886ee3fd-e491-49a9-88a0-9b5f5a2e774c", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 1084, 1088 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "d7f82eda-2b80-4ef8-8240-0f1bd7a5e04f", "type": "title", "text": [ "Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology." ], "offsets": [ [ 0, 104 ] ] }, { "id": "2bdd9638-8172-4f61-a3f6-f171eb7727fe", "type": "abstract", "text": [ "PURPOSE: DNA-damaging factors have been reported in patients that failed to achieve pregnancy after assisted reproductive technologies (ART). The hypothesis was that increased circulating cell-free DNA released by damaged cells could predict unfavorable conditions leading to failed ART treatment. The objective was to compare the relative concentrations of cell-free DNA in the luteal phase sera of nonpregnant versus pregnant patients. METHODS: Frozen-thawed sera (30 IVF cases) were obtained 1 week after embryo transfer. There were 16 pregnant and 14 nonpregnant cases and controls consisting of male sera (n = 8 cases). Modified isocratic capillary electrophoresis was performed and the images analyzed for cell-free DNA. RESULTS: Circulating cell-free DNA were identified in the sera of all patients. The serum concentrations of high (12 kb) and low (1 kb) molecular weight cell-free DNA were similar for both nonpregnant and pregnant patients. Male control sera had higher cell-free DNA concentrations compared with females. Evaluation of sera from a control case showed no fluctuations in cell-free DNA concentrations throughout specific days of the menstrual cycle. CONCLUSIONS: The results do not support the use of the luteal phase cell-free DNA concentration as a marker for failed pregnancies. The equal concentrations of high and low molecular weight cell-free DNA and ladder band-like gel patterns suggested cell apoptosis as the source of DNA." ], "offsets": [ [ 105, 1564 ] ] } ]

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[ { "id": "de8a5e31-7fb8-40eb-8da5-465199d3b4e8", "type": "title", "text": [ "Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome: report of a child with phenotypic overlap with ulnar-mammary syndrome and a new mutation in TP63." ], "offsets": [ [ 0, 150 ] ] }, { "id": "9eec032f-27ed-47aa-a03f-b23e170e3263", "type": "abstract", "text": [ "We report on a new patient with clinical findings consistent with acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome. The child had sparse hair, extensive freckling, lacrimal duct stenosis, oligodontia, dystrophic nails, reduced sweating, and bilateral athelia. Examination of his hands showed ulnar ray hypoplasia with bilateral fifth finger brachydactyly and camptodactyly. He also had surgical repair of an imperforate anus. Mutation analysis of TP63 showed a single nucleotide substitution, c.G518A, predicting a novel missense mutation, p.V114M in exon 4. This is the third mutation to be reported in TP63 in ADULT syndrome." ], "offsets": [ [ 151, 781 ] ] } ]

[ { "id": "23588cd9-4c7d-4a43-b193-b38aa874206c", "type": "Gene", "text": [ "TP63" ], "offsets": [ [ 145, 149 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "adc5799a-50c7-44bb-877e-3781084fc079", "type": "Gene", "text": [ "TP63" ], "offsets": [ [ 601, 605 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e2e53787-cf64-4c44-b52e-a95a366d1335", "type": "Gene", "text": [ "TP63" ], "offsets": [ [ 758, 762 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "783a7860-71a6-4c63-83a2-b2b05d47c6de", "type": "title", "text": [ "Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families." ], "offsets": [ [ 0, 144 ] ] }, { "id": "9e1f9418-0b8e-4ea4-a58e-de3e4da086f6", "type": "abstract", "text": [ "Recent reports have demonstrated that mutations in the OPHN1 gene were responsible for a syndromic rather than non-specific mental retardation. Abnormalities of the posterior fossa with cerebellar hypoplasia have been demonstrated in all male patients reported to date. We report here a new family with X-linked mental retardation due to mutation in OPHN1 and present unpublished data about two families previously reported, concerning the facial and psychological phenotype of affected males and carrier females. Our study confirms that cerebellar hypoplasia is a hallmark of this syndrome. In addition, affected males display facial similarities that can help the diagnosis. Most carrier females have mild mental retardation and subtle facial changes." ], "offsets": [ [ 145, 898 ] ] } ]

[ { "id": "708486e6-1b2e-4889-9a07-1807285d226d", "type": "Gene", "text": [ "OPHN1" ], "offsets": [ [ 54, 59 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "17b81b1d-fdb4-4c68-9d8d-1d6907761621", "type": "Gene", "text": [ "OPHN1" ], "offsets": [ [ 200, 205 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e757c7a1-b28c-4149-bbcf-d10668ae79ee", "type": "Gene", "text": [ "OPHN1" ], "offsets": [ [ 495, 500 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "7608a890-66a4-4f82-9599-88e4b4e16dce", "type": "title", "text": [ "Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation." ], "offsets": [ [ 0, 93 ] ] }, { "id": "a713e0ef-d782-4e11-a6e1-7960a718470d", "type": "abstract", "text": [ "In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere." ], "offsets": [ [ 94, 1404 ] ] } ]

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[ { "id": "63e055e4-00d0-4524-accc-9b53b99d8829", "type": "title", "text": [ "NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory." ], "offsets": [ [ 0, 89 ] ] }, { "id": "a1b1ea65-726c-4f1f-a2ce-edc3625e41ad", "type": "abstract", "text": [ "PURPOSE: Sotos syndrome is a genetic disorder characterized primarily by overgrowth, developmental delay, and a characteristic facial gestalt. Defects in the NSD1 gene are present in approximately 80% of patients with Sotos syndrome. The goal of this study was to determine the incidence of NSD1 abnormalities in patients referred to a clinical laboratory for testing and to identify clinical criteria that distinguish between patients with and without NSD1 abnormalities. METHODS: Deletion or mutation analysis of the NSD1 gene was performed on 435 patients referred to our clinical genetics laboratory. Detailed clinical information was obtained on 86 patients with and without NSD1 abnormalities, and a clinical checklist was developed to help distinguish between these two groups of patients. RESULTS: Abnormalities of the NSD1 gene were identified in 55 patients, including 9 deletions and 46 mutations. Thus, in the clinical laboratory setting, deletions were found in 2% and mutations in 21% of samples analyzed, because not all patients had both tests. Thirty-three previously unreported mutations in the NSD1 gene were identified. Clinical features typically associated with Sotos syndrome were not found to be significantly different between individuals with and without NSD1 abnormalities. The clinical checklist developed included poor feeding, increased body mass index, and enlarged cerebral ventricles, in addition to the typical clinical features of Sotos syndrome, and was able to distinguish between the two groups with 80% sensitivity and 70% specificity. CONCLUSIONS: The dramatic decrease in the frequency of finding NSD1 abnormalities in the clinical laboratory is likely because of the heterogeneity of the patient population. Our experience from a diagnostic laboratory can help guide clinicians in deciding for whom NSD1 genetic analysis is indicated." ], "offsets": [ [ 90, 1966 ] ] } ]

[ { "id": "010582f4-6967-4020-8b8c-f01f2b791f15", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 0, 4 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5fefa0ad-b1ca-4d18-8b9e-f8184a9931a3", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 248, 252 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fa6f974f-0bc2-4fa0-b5dc-b5ce5f2b941a", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 381, 385 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "55417a34-efbe-42f1-9d29-4be53bc7b37b", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 543, 547 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "154cba66-20f5-47b7-9cf7-5d33cd339742", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 609, 613 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "31ebf775-a4fc-4ac4-9c6a-f1f2614430e3", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 770, 774 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "acf20520-a2bd-4055-a603-26850a6024af", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 917, 921 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1598acb3-d278-4ec8-bd1d-5c7b41566d5f", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 1203, 1207 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fdde7360-307e-43e2-923e-e4322ef3d47f", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 1371, 1375 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4676bb95-98ba-4ed9-b93a-9014d5e601cb", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 1728, 1732 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "956a79c7-1331-4896-8294-46e35488b28c", "type": "Gene", "text": [ "NSD1" ], "offsets": [ [ 1931, 1935 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "324c2db0-7a55-4942-a638-555f6be20869", "type": "title", "text": [ "Rarity of IgH translocations in Waldenstrom macroglobulinemia." ], "offsets": [ [ 0, 62 ] ] }, { "id": "a87de02b-94af-4b2e-8fed-8a6b888501c4", "type": "abstract", "text": [ "Comparatively little is known of the cytogenetics of Waldenstrom macroglobulinemia (WM). This is primarily due to the low proliferation of the clonal B cells, which precludes conventional karyotyping in many cases. Translocations involving the immunoglobulin heavy chain (IGH) gene at 14q32 are characteristic of many B-cell lymphomas and myelomas. Initial reports suggested that the t(9;14) was characteristic of lymphoplasmacytic lymphoma (the underlying pathological diagnosis in WM), but subsequent studies have failed to confirm the uniqueness of the translocation. To clarify this, we examined 69 cases of WM with interphase fluorescence in situ hybridization and failed to demonstrate an IgH translocation in 67 (97%). We conclude that IGH translocations are not a feature of WM, and the implications of this finding are discussed." ], "offsets": [ [ 63, 901 ] ] } ]

[ { "id": "67db44bc-eacf-45f2-a2eb-86710c847ba8", "type": "Gene", "text": [ "IgH" ], "offsets": [ [ 10, 13 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "82c55171-1615-46e6-9578-8f963332635a", "type": "Gene", "text": [ "immunoglobulin heavy chain" ], "offsets": [ [ 307, 333 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4d8f4f38-5a9c-4259-bb02-4bd7e32c5fa1", "type": "Gene", "text": [ "IGH" ], "offsets": [ [ 335, 338 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "20d11a36-7646-4870-afea-c3b08175ee6e", "type": "Gene", "text": [ "IgH" ], "offsets": [ [ 758, 761 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0a2b5f36-c89c-4b85-85da-edd898c75d8a", "type": "Gene", "text": [ "IGH" ], "offsets": [ [ 806, 809 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "6204e66c-d41c-4024-a1de-0c07ead2a55e", "type": "title", "text": [ "IL-1 receptor antagonist attenuates MAP kinase/AP-1 activation and MMP1 expression in UVA-irradiated human fibroblasts induced by culture medium from UVB-irradiated human skin keratinocytes." ], "offsets": [ [ 0, 190 ] ] }, { "id": "512be4c5-cc8c-4bdf-9332-0b25c2a06b7d", "type": "abstract", "text": [ "Solar UV light comprises UVB wavelengths (290-320 nm) and UVA wavelengths (320-400 nm). UVB radiation reaches the epidermis and, to a lesser extent, the upper part of the dermis, while UVA radiation penetrates more deeply into human skin. Existing studies have demonstrated that UV-irradiated epidermal keratinocytes release cytokines that indirectly promote MMP-1 production in dermal fibroblasts. In this study, we first investigated the effect of IL-1 on MAPK activity, c-Jun and c-Fos mRNA expression, and MMP-1 and MMP-2 production in UVA-irradiated human dermal fibroblasts. The results showed that UVA irradiation dose-dependently increased MMP-1 but not MMP-2 production in human skin fibroblasts. IL-1alpha and IL-1beta promoted MMP-1 but not MMP-2 production in UVA-irradiated fibroblasts. Both IL-1alpha and IL-1beta activated MAP kinase, significantly elevating c-Jun and c-Fos mRNA expression. We then investigated the indirect effect of UVB-irradiated keratinocyte culture medium on MMP-1 production in UVA-irradiated primary cultured human dermal fibroblasts and the effect of IL-1Ra. The results showed that cell culture medium from UVB-irradiated keratinocytes increased MMP-1 production in UVA-irradiated fibroblasts, and IL-1Ra dose-dependently inhibited MMP-1 production. IL-1Ra dose-dependently inhibited c-Jun mRNA expression of fibroblasts with no significant effect on c-Fos mRNA expression. These results demonstrate that UVB-irradiated keratinocytes promoted MMP-1 production in UVA-irradiated fibroblasts in a paracrine manner while IL-1Ra reduced MMP-1 production through inhibiting c-Jun mRNA expression. Collectively, our data suggest that IL-1 plays an important role in the dermal collagen degradation associated with UV-induced premature aging of the skin and IL-1Ra may be applied for the prevention and treatment of photoaging." ], "offsets": [ [ 191, 2053 ] ] } ]

[ { "id": "9a9a97a4-d04b-4c14-8f97-d049a9d2738b", "type": "Gene", "text": [ "IL-1 receptor antagonist" ], "offsets": [ [ 0, 24 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "39e7d7f5-9873-4cb9-b510-40539910f814", "type": "FamilyName", "text": [ "MAP kinase" ], "offsets": [ [ 36, 46 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f4e3e154-37dd-41ac-b276-5d6ce75b9593", "type": "FamilyName", "text": [ "AP-1" ], "offsets": [ [ 47, 51 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ca7594a8-277c-4af6-a50d-4058ba733500", "type": "Gene", "text": [ "MMP1" ], "offsets": [ [ 67, 71 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "687f371b-d555-422e-81b7-6f5c47fd330b", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 550, 555 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eed4983b-5199-4e86-b627-661add52cd38", "type": "Gene", "text": [ "IL-1" ], "offsets": [ [ 641, 645 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ebe9b3fa-339d-4793-98c1-e5637a2d64a4", "type": "FamilyName", "text": [ "MAPK" ], "offsets": [ [ 649, 653 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "19753db3-a2b9-4f7b-bafd-db027851f0f4", "type": "Gene", "text": [ "c-Jun" ], "offsets": [ [ 664, 669 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3af04c26-53d6-4c26-bed7-84286ffddec4", "type": "Gene", "text": [ "c-Fos" ], "offsets": [ [ 674, 679 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9572e89f-e430-4ac7-a3a5-0e2587c7d696", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 701, 706 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1f3c677a-313b-4363-abbc-cfd5e6afdb49", "type": "Gene", "text": [ "MMP-2" ], "offsets": [ [ 711, 716 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "77c1f400-8578-444e-996c-086330dab8fe", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 839, 844 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8acff8f2-d3c5-4883-9632-35354ba1b629", "type": "Gene", "text": [ "MMP-2" ], "offsets": [ [ 853, 858 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "52985374-ee00-466f-b080-250752443ecd", "type": "Gene", "text": [ "IL-1alpha" ], "offsets": [ [ 897, 906 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a611c4ac-6a2e-40c6-b5cb-54bad106c4bf", "type": "Gene", "text": [ "IL-1beta" ], "offsets": [ [ 911, 919 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6051c4b5-bcd7-4555-861c-0eabdcc01c81", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 929, 934 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d5ac1e55-7cc1-40db-b9c7-e70a7ff2a6e9", "type": "Gene", "text": [ "MMP-2" ], "offsets": [ [ 943, 948 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7c53d6d1-342e-4276-891d-81ab99c37674", "type": "Gene", "text": [ "IL-1alpha" ], "offsets": [ [ 996, 1005 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e9379167-dba9-4592-9cda-d7402647f17f", "type": "Gene", "text": [ "IL-1beta" ], "offsets": [ [ 1010, 1018 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0062d804-ef7d-4694-a929-b762de31bdc5", "type": "FamilyName", "text": [ "MAP" ], "offsets": [ [ 1029, 1032 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "42177e62-7888-4e25-afb8-e3d1831477e2", "type": "Gene", "text": [ "c-Jun" ], "offsets": [ [ 1065, 1070 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c830f2c6-ddd9-4bac-9199-85cf6d9fe212", "type": "Gene", "text": [ "c-Fos" ], "offsets": [ [ 1075, 1080 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6c20984b-64f8-46e9-a0e1-ce232c6196bb", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 1188, 1193 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d5d8b76b-0c05-47fa-8c26-6282d511b0d3", "type": "Gene", "text": [ "IL-1Ra" ], "offsets": [ [ 1283, 1289 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7d81f016-17a1-4ab1-b9db-8baf25f3bdc8", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 1379, 1384 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8b84d53c-f848-41e7-ba24-96ec84668250", "type": "Gene", "text": [ "IL-1Ra" ], "offsets": [ [ 1431, 1437 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0981977c-8f79-4073-bf9c-2ace5147b0d4", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 1465, 1470 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bdcacf6d-bf0a-4124-9fdd-8f4b0611a49e", "type": "Gene", "text": [ "IL-1Ra" ], "offsets": [ [ 1483, 1489 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ef18ff51-6b53-4949-be6b-60c68986d89d", "type": "Gene", "text": [ "c-Jun" ], "offsets": [ [ 1517, 1522 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "abdf7c4e-1835-4830-83f0-1de379636d20", "type": "Gene", "text": [ "c-Fos" ], "offsets": [ [ 1584, 1589 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "791a5ad0-4110-4965-8427-0dacc95ec737", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 1676, 1681 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e588baa7-126d-4171-bea5-79119023e9f4", "type": "Gene", "text": [ "IL-1Ra" ], "offsets": [ [ 1751, 1757 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f64cfbb7-b860-467a-9e48-f585c9b73d9e", "type": "Gene", "text": [ "MMP-1" ], "offsets": [ [ 1766, 1771 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b32e5abb-595d-4f04-8b9a-5619e215bdd2", "type": "Gene", "text": [ "c-Jun" ], "offsets": [ [ 1802, 1807 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2e92c16d-1756-4cab-a30c-d53fdbe03c2c", "type": "Gene", "text": [ "IL-1" ], "offsets": [ [ 1861, 1865 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "01241d83-8394-4b24-886f-ea0039454564", "type": "Gene", "text": [ "IL-1Ra" ], "offsets": [ [ 1984, 1990 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "478770c3-aa33-4c08-ae50-cf9d6b44fa34", "type": "title", "text": [ "Temporal and parental-specific expression of imprinted genes in a newly derived Chinese human embryonic stem cell line and embryoid bodies." ], "offsets": [ [ 0, 139 ] ] }, { "id": "d33112cb-6b22-4827-9edc-1714dfe8617e", "type": "abstract", "text": [ "Although the study of imprinted genes in human development is very important, little is known about their expression and regulation in the early differentiation of human tissues due to lack of an appropriate model. In this study, a Chinese human embryonic stem (hES) cell line, SHhES1, was derived and fully characterized. Expression profiles of human imprinted genes were determined by Affymetrix Oligo micro-array in undifferentiated SHhES1 cells and SHhES1-derived embryoid bodies (EBs) at day 3, 8, 13 and 18. Thirty-two known human imprinted genes were detected in undifferentiated ES cells. Significantly, differential expression was found in nine genes at different stages of EB formation. Expression profile changes were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction in SHhES1 cells as well as in another independently derived hES cell line, HUES-7. In addition, the monoallelic expressions of four imprinted genes were examined in three different passages of undifferentiated ES cells and EBs of both hES cell lines. The monoallelic expressions of imprinted genes, H19, PEG10, NDNL1 and KCNQ1 were maintained in both undifferentiated hES cells and derived EBs. More importantly, with the availability of maternal peripheral blood lymphocyte sample, we demonstrated that the maternal expression of KCNQ1 and the paternal expression of NDNL1 and PEG10 were maintained in SHhES1 cells. These data provide the first demonstration that the parental-specific expression of imprinted genes is stable in EBs after extensive differentiation, also indicating that in vitro fertilization protocol does not disrupt the parental monoallelic expression of the imprinted genes examined." ], "offsets": [ [ 140, 1858 ] ] } ]

[ { "id": "9223e8d9-a751-4d6c-a9e8-39478d284482", "type": "Gene", "text": [ "H19" ], "offsets": [ [ 1252, 1255 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1b7f56db-67d9-4e87-9f6f-e2b8e258ceee", "type": "Gene", "text": [ "PEG10" ], "offsets": [ [ 1257, 1262 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7bf39590-bd43-4aeb-a015-5fd3bbc7aafd", "type": "Gene", "text": [ "NDNL1" ], "offsets": [ [ 1264, 1269 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cd02f004-d902-44b3-b15e-6e85c0018b8d", "type": "Gene", "text": [ "KCNQ1" ], "offsets": [ [ 1274, 1279 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "950eb9cd-f669-4e2c-8c33-040b2e66a935", "type": "Gene", "text": [ "KCNQ1" ], "offsets": [ [ 1484, 1489 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dc7db7f2-56dc-4be1-820f-0f147eed19e7", "type": "Gene", "text": [ "NDNL1" ], "offsets": [ [ 1521, 1526 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "561b7bfc-58e2-4ab3-af1f-d63ca962724d", "type": "Gene", "text": [ "PEG10" ], "offsets": [ [ 1531, 1536 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "21c0078e-f038-45af-857d-aa4a593b6de5", "type": "title", "text": [ "A comparison of folic acid deficiency-induced genomic instability in lymphocytes of breast cancer patients and normal non-cancer controls from a Chinese population in Yunnan." ], "offsets": [ [ 0, 174 ] ] }, { "id": "92f2454c-50fe-492c-9ddc-49dc064eaf0d", "type": "abstract", "text": [ "We hypothesized that the genomic response to folate deficiency might be different between breast cancer cases and healthy subjects. To test this hypothesis, we performed a comprehensive study on the genotoxic and cytotoxic effects of in vitro folic acid (FA) deficiency on primary human lymphocytes from 19 breast cancer patients and 20 age-matched healthy females from Yunnan, China using the cytokinesis-block micronucleus assay. Lymphocytes from the volunteers were cultured in RPMI1640 medium containing 30, 120 or 240 nM FA for 9 days. The results showed that 30 nM FA was associated with increased frequencies of micronucleated binucleated cell (MNed BNC), nucleoplasmic bridges (NPB), nuclear buds (BUD), apoptosis (APO) and necrosis (NEC) relative to 120 and 240 nM FA (P<0.001) in lymphocytes of case and control groups in vitro, however there were no significant differences between the 120 and 240 nM FA within each sampling group. The case group showed significantly higher frequencies of MNed BNC than control at 120 and 240 nM FA (P<0.05-0.001) but not at 30 nM FA (P=0.052). NEC was significantly higher in breast cancer group than control at all concentrations of FA (P<0.005). FA concentration explained 60, 39, 39, 52 and 71% of the variance of MNed BNC, NPB, BUD, APO and NEC, respectively compared with breast cancer status which only explained 6 and 7% of the variance of MNed BNC and NEC(Two way ANOVA, P<0.0001). Difference of difference analysis showed that breast cancer cases were not abnormally sensitive to the genome-damaging effect of folate deficiency. We concluded that (i) increased concentrations of FA abolished the genome-damaging effect of FA deficiency in lymphocytes of both breast cancer patients and controls to a similar extent and (ii) FA concentration is much more important than breast cancer status in determining genomic instability and cell death." ], "offsets": [ [ 175, 2082 ] ] } ]

[ { "id": "2fb0b7ae-2118-4cd5-9ef7-612bf450e060", "type": "Gene", "text": [ "APO" ], "offsets": [ [ 898, 901 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7b900364-941e-4a0b-a277-8546c46d4442", "type": "Gene", "text": [ "APO" ], "offsets": [ [ 1467, 1470 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "ca0deff3-a1c1-412d-96ab-e02b009f2f10", "type": "title", "text": [ "Evaluating the role of the 620W allele of protein tyrosine phosphatase PTPN22 in Crohn's disease and multiple sclerosis." ], "offsets": [ [ 0, 125 ] ] }, { "id": "b34f95b3-969a-432e-919b-ff9ef1f14015", "type": "abstract", "text": [ "The 620W allele of PTPN22 has been associated with susceptibility to several different forms of chronic inflammatory disease, including Type 1 diabetes (T1D), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroiditis (AIT). We set out to explore its possible role in two other inflammatory diseases: multiple sclerosis (MS) and Crohn's disease (CD). In our cohort of 496 MS trios from the United Kingdom, we observed reduced transmission of the PTPN22 620W allele. The CD sample consisted of 169 trios as well as 249 cases of CD with their 207 matched control subjects collected in the province of Quebec, Canada; there was also no evidence of association between the PTPN22 620W allele and susceptibility for CD. Pooled analyses combining our data with published data assessed a total of 1496 cases of MS and 1019 cases of CD but demonstrated no evidence of association with either disease. Given the modest odds ratios of known risk alleles for inflammatory diseases, these analyses do not exclude a role for the PTPN22 allele in susceptibility to CD or MS, but they do suggest that such a putative role would probably be more modest than that reported so far in T1D, RA, SLE, and AIT." ], "offsets": [ [ 126, 1350 ] ] } ]

[ { "id": "8f71353b-3ba8-4453-aeab-b552d9501f2b", "type": "Gene", "text": [ "protein tyrosine phosphatase" ], "offsets": [ [ 42, 70 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1aa40be5-2ba7-4bad-a3e5-f85add958053", "type": "Gene", "text": [ "PTPN22" ], "offsets": [ [ 71, 77 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0ee797b4-40b2-46e7-b672-0ebae9ea3c55", "type": "Gene", "text": [ "PTPN22" ], "offsets": [ [ 145, 151 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dacd0273-de8a-4771-b1cc-e5527055bdd6", "type": "Gene", "text": [ "PTPN22" ], "offsets": [ [ 608, 614 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fb917a91-31ca-4d9b-aed4-bb9e6091b6f2", "type": "Gene", "text": [ "PTPN22" ], "offsets": [ [ 831, 837 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d37a4b8c-e414-47a7-8936-c3bcc3b53697", "type": "Gene", "text": [ "PTPN22" ], "offsets": [ [ 1178, 1184 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "91ff2d6f-efb0-4dae-9f44-bb4ec2824c24", "type": "title", "text": [ "Peroxisomal proliferator activated receptor-gamma deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3)." ], "offsets": [ [ 0, 134 ] ] }, { "id": "ddc73c52-d90e-4535-b297-cbf6d16d5859", "type": "abstract", "text": [ "BACKGROUND: Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-gamma. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition. METHODS: We present a Canadian FPLD3 kindred with an affected mother who had loss of fat on arms and legs, but no increase in facial, neck, suprascapular or abdominal fat. She had profound insulin resistance, diabetes, severe hypertriglyceridemia and relapsing pancreatitis, while her pre-pubescent daughter had normal fat distribution but elevated plasma triglycerides and C-peptide and depressed high-density lipoprotein cholesterol. RESULTS: The mother and daughter were each heterozygous for PPARG nonsense mutation Y355X, whose protein product in vitro was transcriptionally inactive with no dominant-negative activity against the wild-type receptor. In addition the mutant protein appeared to be markedly unstable. CONCLUSION: Taken together with previous studies of human PPARG mutations, these findings suggest that PPAR-gamma deficiency due either to haploinsufficiency or to substantial activity loss due to dominant negative interference of the normal allele product's function can each contribute to the FPLD3 phenotype." ], "offsets": [ [ 135, 1486 ] ] } ]

[ { "id": "528c5953-00a1-47c9-b41d-e0b357e6a810", "type": "Gene", "text": [ "Peroxisomal proliferator activated receptor-gamma" ], "offsets": [ [ 0, 49 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2a2922c6-f63b-4897-9b28-49d90da62add", "type": "Gene", "text": [ "PPARG" ], "offsets": [ [ 286, 291 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a12e1dbe-440a-4ee8-9799-bd3c8f597fc1", "type": "Gene", "text": [ "peroxisomal proliferator-activated receptor-gamma" ], "offsets": [ [ 301, 350 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0dcc4e35-987b-4622-bf9d-747d66f9aa25", "type": "Gene", "text": [ "insulin" ], "offsets": [ [ 638, 645 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "261cd0d3-25f8-4b16-8fc4-45c5ca214e18", "type": "Gene", "text": [ "PPARG" ], "offsets": [ [ 945, 950 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9911cb69-5cfe-40a5-ad6d-3ef659de0e83", "type": "FamilyName", "text": [ "wild-type receptor" ], "offsets": [ [ 1085, 1103 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5c12d4bf-27ac-43b4-bc39-15202797efd1", "type": "Gene", "text": [ "PPARG" ], "offsets": [ [ 1228, 1233 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "82aa6a55-193f-4c0d-bfbb-16c5f1fa0a08", "type": "Gene", "text": [ "PPAR-gamma" ], "offsets": [ [ 1273, 1283 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "7f41a16c-aa3b-4837-a96e-eb4572068dce", "type": "title", "text": [ "The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis." ], "offsets": [ [ 0, 127 ] ] }, { "id": "8ed6e092-81fd-49fd-8feb-833032a7c421", "type": "abstract", "text": [ "The CFTR mutations in cystic fibrosis (CF) lead to ion transport anomalities which predispose to chronic infection and inflammation of CF airways as the major determinants for morbidity and mortality in CF. Discordant clinical phenotypes of siblings with identical CFTR mutations and the large variability of clinical manifestations of patients who are homozygous for the most common mutation F508del suggest that both environment and genes other than CFTR contribute substantially to CF disease. The prime candidates for genetic modifiers in CF are elements of host defence such as the TNFalpha receptor and of ion transport such as the amiloride-sensitive epithelial sodium channel ENaC, both of which are encoded side by side on 12p13 (TNFRSF1A, SCNN1A) and 16p12 (SCNN1B, SCNN1G). Thirty-seven families with F508del-CFTR homozygous siblings exhibiting extreme clinical phenotypes that had been selected from the 467 pairs of the European CF Twin and Sibling Study were genotyped at 12p13 and 16p12 markers. The ENaC was identified as a modulator of CF by transmission disequilibrium at SCNN1G and association with CF phenotype intrapair discordance at SCNN1B. Family-based and case-control analyses and sequencing of SCNN1A and TNFRSF1A uncovered an association of the TNFRSF1A intron 1 haplotype with disease severity. Carriers of risk haplotypes were underrepresented suggesting a strong impact of both loci on survival. The finding that TNFRSF1A, SCNN1B and SCNN1G are clinically relevant modulators of CF disease supports current concepts that the depletion of airway surface liquid and inadequate host inflammatory responses trigger pulmonary disease in CF." ], "offsets": [ [ 128, 1794 ] ] } ]

[ { "id": "732f73b2-0804-4539-8b23-d99ddc60a61c", "type": "FamilyName", "text": [ "TNFalpha receptor" ], "offsets": [ [ 4, 21 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "043b3fc3-b8ac-4b75-a335-5be854090e59", "type": "Gene", "text": [ "TNFRSF1A" ], "offsets": [ [ 22, 30 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "542aa11c-0fcf-49c9-a9c0-417049fd0d0f", "type": "FamilyName", "text": [ "amiloride-sensitive sodium channel" ], "offsets": [ [ 54, 88 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "84ff2bd8-17bc-4441-ad77-38d1a3a14092", "type": "FamilyName", "text": [ "ENaC" ], "offsets": [ [ 89, 93 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "36ba7356-5bb2-4229-aea6-207ddc3331ff", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 132, 136 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6ed091c3-119c-48fd-be66-e6d00bb87efc", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 393, 397 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a7920e20-2f0d-4836-9469-943ec3f0db96", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 580, 584 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1aa0379b-561f-48da-a924-e44973049a49", "type": "FamilyName", "text": [ "TNFalpha receptor" ], "offsets": [ [ 715, 732 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "856d2bf1-ef93-4e4c-a37a-c0322b3dde78", "type": "FamilyName", "text": [ "amiloride-sensitive epithelial sodium channel" ], "offsets": [ [ 766, 811 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4cd783d3-6677-4870-b72f-bd8fdd5b86e4", "type": "FamilyName", "text": [ "ENaC" ], "offsets": [ [ 812, 816 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "252bc767-a2b4-43f8-9bb9-4e97ed76e571", "type": "Gene", "text": [ "TNFRSF1A" ], "offsets": [ [ 867, 875 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "aa7ec447-6475-4e9f-8d8c-5feda3c6bce3", "type": "Gene", "text": [ "SCNN1A" ], "offsets": [ [ 877, 883 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3613922b-4970-4809-828b-4b1b32dfb616", "type": "Gene", "text": [ "SCNN1B" ], "offsets": [ [ 896, 902 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5a1d5a0d-8b88-4384-8141-0f8103ddc842", "type": "Gene", "text": [ "SCNN1G" ], "offsets": [ [ 904, 910 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ecec630c-f457-424c-839d-0ed912290243", "type": "Gene", "text": [ "CFTR" ], "offsets": [ [ 948, 952 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7d78851f-f497-40c2-a012-b3d73f36a992", "type": "FamilyName", "text": [ "ENaC" ], "offsets": [ [ 1143, 1147 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6b49fe2e-9df2-4fa2-a3b0-7756057ea203", "type": "Gene", "text": [ "SCNN1G" ], "offsets": [ [ 1218, 1224 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "749bc0e4-1f29-424d-a067-9194c1d3ffa7", "type": "Gene", "text": [ "SCNN1B" ], "offsets": [ [ 1284, 1290 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "38983c7c-656b-4dc3-a6df-479384468a1c", "type": "Gene", "text": [ "SCNN1A" ], "offsets": [ [ 1349, 1355 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f36d30a6-0f53-4129-974d-ef3b4175e574", "type": "Gene", "text": [ "TNFRSF1A" ], "offsets": [ [ 1360, 1368 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a7850937-d60c-4252-b73c-f020329b4c2f", "type": "Gene", "text": [ "TNFRSF1A" ], "offsets": [ [ 1401, 1409 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e4003213-0cec-4a8a-aded-49f182e6abc4", "type": "Gene", "text": [ "TNFRSF1A" ], "offsets": [ [ 1572, 1580 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e2204edf-e11c-4948-9bb5-84ffb3c9e74f", "type": "Gene", "text": [ "SCNN1B" ], "offsets": [ [ 1582, 1588 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c72e21b1-336d-4608-a32f-f2200a3d7ed5", "type": "Gene", "text": [ "SCNN1G" ], "offsets": [ [ 1593, 1599 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "4d44965d-853f-4fbd-baa5-e49b9a64bbdf", "type": "title", "text": [ "Chiari type I malformation in four unrelated patients affected with Fabry disease." ], "offsets": [ [ 0, 82 ] ] }, { "id": "315c8767-edec-43c5-9e63-adfab2ce7d74", "type": "abstract", "text": [ "Fabry disease (FD) is an X-linked inborn error of metabolism resulting from the deficient activity of alpha-galactosidase A which leads to the widespread deposition of glycosphingolipids in lysosomes, and to ischemic complications involving kidneys, heart and brain. Among neurological symptoms, strokes and transient ischemic attacks (TIA) have been reported. A 30-year-old male patient, with FD, was referred to us for evaluation of a sudden episode of dizziness, with disequilibrium, and diplopia, in agreement with the diagnosis of a TIA. Head magnetic resonance imaging (MRI) showed no cerebrovascular involvement but revealed the presence of Chiari type I malformation (CMI). We subsequently performed head MRI in a cohort of 44 consecutive hemizygous male patients and seven heterozygous females affected with FD, and identified three additional cases (two males and one female) of CMI. Whether the association is coincidental or not will need further studies but our data suggest that CMI should be ruled out in all Fabry patients." ], "offsets": [ [ 83, 1122 ] ] } ]

[ { "id": "1be4a3bc-3550-47a7-bccd-bd4c5c27ab80", "type": "Gene", "text": [ "alpha-galactosidase A" ], "offsets": [ [ 185, 206 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "418d46c6-d48e-40c1-8b51-6ac9062a19ad", "type": "title", "text": [ "Fibrin sealant promotes migration and proliferation of human articular chondrocytes: possible involvement of thrombin and protease-activated receptors." ], "offsets": [ [ 0, 151 ] ] }, { "id": "c7984e2f-f6b6-4bab-8513-28d281b0c730", "type": "abstract", "text": [ "Fibrin sealant (FS), a biological adhesive material, has been recently recommended as an adjunct in autologous chondrocyte implantation (ACI). While FS has been shown to possess osteoinductive potential, little is known about its effects on chondrogenic cells. In this study, we assessed the bioactivity of FS (Tisseel) on the migration and proliferation of human articular chondrocytes in vitro. Using a co-culture assay to mimic matrix-induced ACI (MACI), chondrocytes were found to migrate from collagen membranes towards FS within 12 h of culture, with significant migratory activity evident by 24 h. In addition, 5-bromo-2'-deoxyuridine (BrdU) incorporation experiments revealed that thrombin, the active component of the tissue glue, stimulated chondrocyte proliferation, with maximal efficacy observed at 48 h post-stimulation (1-10 U/ml). In an effort to elucidate the molecular mechanisms underlying these thrombin-induced effects, we examined the expression and activation of protease-activated receptors (PARs), established thrombin receptors. Using a combination of RT-PCR and immunohistochemistry, all four PARs were detected in human chondrocytes, with PAR-1 being the major isoform expressed. Moreover, thrombin and a PAR-1, but not other PAR-isotype-specific peptide agonists, were found to induce rapid intracellular Ca2+ responses in human chondrocytes in calcium mobilization assays. Together, these data demonstrate that FS supports both the migration and proliferation of human chondrocytes. We propose that these effects are mediated, at least in part, via thrombin-induced PAR-1 signalling in human chondrocytes." ], "offsets": [ [ 152, 1792 ] ] } ]

[ { "id": "de010bda-4152-45b4-97c6-79781f4112aa", "type": "Gene", "text": [ "thrombin" ], "offsets": [ [ 109, 117 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4abd3e59-a080-426e-84f5-5ebe75448960", "type": "FamilyName", "text": [ "protease-activated receptors" ], "offsets": [ [ 122, 150 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d35580c3-370f-42c5-ae72-886af0130796", "type": "Gene", "text": [ "thrombin" ], "offsets": [ [ 846, 854 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a1de7253-e74c-4cd4-86b3-6286b0f0ef5c", "type": "Gene", "text": [ "thrombin" ], "offsets": [ [ 1072, 1080 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9c11dcba-15a0-4a69-8d76-56d5a25fc4ae", "type": "FamilyName", "text": [ "protease-activated receptors" ], "offsets": [ [ 1143, 1171 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2846be73-4c40-49b4-9c0a-b120348f2f41", "type": "FamilyName", "text": [ "PARs" ], "offsets": [ [ 1173, 1177 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "470865b1-84ef-48c4-976b-3f02ed5f327f", "type": "FamilyName", "text": [ "thrombin receptors" ], "offsets": [ [ 1192, 1210 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6f3443d2-3d62-4344-9b46-655ce75376a8", "type": "FamilyName", "text": [ "PARs" ], "offsets": [ [ 1277, 1281 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "be738123-78e8-43a6-94ed-33852a7eaab6", "type": "Gene", "text": [ "PAR-1" ], "offsets": [ [ 1324, 1329 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f5ac0fc8-1965-4b43-8c0c-6ae5a619d826", "type": "Gene", "text": [ "thrombin" ], "offsets": [ [ 1375, 1383 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "93c82968-a7b1-47a8-be05-bcae177b60b9", "type": "Gene", "text": [ "PAR-1" ], "offsets": [ [ 1390, 1395 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "574ce629-0f51-4c92-b207-eabaf06fdc24", "type": "FamilyName", "text": [ "PAR" ], "offsets": [ [ 1411, 1414 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7dfe597b-7c8e-4c32-bef7-06d27b600386", "type": "Gene", "text": [ "thrombin" ], "offsets": [ [ 1736, 1744 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dcad6edf-5f11-4e89-9ec1-731ff0a19787", "type": "Gene", "text": [ "PAR-1" ], "offsets": [ [ 1753, 1758 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "43d42a59-66a4-4d18-bba5-bd2abd585dbc", "type": "title", "text": [ "WISP-2 expression in human salivary gland tumors." ], "offsets": [ [ 0, 49 ] ] }, { "id": "8136ca88-a991-4019-9781-9ce84f6e52d1", "type": "abstract", "text": [ "This study was designed to disclose detailed genetic mechanisms in salivary gland tumors (SGTs) for development of novel independent marker. We constructed an in-house cDNA microarray carrying 2,201 cDNA clones derived from SGT and oral squamous cell carcinoma cDNA libraries. Four cell lines that originated from the SGT-derived cell lines were analyzed using this microarray system. The genes identified by our microarray system were further analyzed at the mRNA or protein expression level in other types of human cancer cell lines and clinical samples (ten normal salivary glands [NSGs], eleven pleomorphic adenomas, ten adenoid cystic carcinomas and three adenocarcinomas). Two up-regulated genes and six down-regulated genes were identified in common when compared with the control RNA. Of the up-regulated genes, WISP-2, which plays an important role in breast carcinogenesis, was selected for further analyses. We found a higher expression of the WISP-2 gene in the SGT-derived cell lines compared with other types of human cancer cell lines. Furthermore, WISP-2 mRNA and protein expression levels in NSGs were significantly higher than those in SGTs. These results suggest that WISP-2 could be a reliable independent marker and that down-regulation or loss of the WISP-2 gene may be associated with the development of SGTs." ], "offsets": [ [ 50, 1382 ] ] } ]

[ { "id": "b96c29d2-f2e9-4266-bdcf-83aa1c0a3f8e", "type": "Gene", "text": [ "WISP-2" ], "offsets": [ [ 0, 6 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "526b5a51-d5af-43cf-9ff8-2bb70ecf11a5", "type": "Gene", "text": [ "WISP-2" ], "offsets": [ [ 870, 876 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "62b9e451-7da7-4f32-8a51-ff3369d51fe8", "type": "Gene", "text": [ "WISP-2" ], "offsets": [ [ 1005, 1011 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b5bbe2e2-5b23-443c-baf2-18375dfcc5fa", "type": "Gene", "text": [ "WISP-2" ], "offsets": [ [ 1114, 1120 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0f67d24a-cb45-435d-8feb-e1cab15aad73", "type": "Gene", "text": [ "WISP-2" ], "offsets": [ [ 1237, 1243 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0f1f0cb4-e07a-4614-866e-6bcb16bc1533", "type": "Gene", "text": [ "WISP-2" ], "offsets": [ [ 1323, 1329 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "a90e0c68-3451-42e1-9051-7038b5d1ac2c", "type": "title", "text": [ "Evaluation of RGS4 as a candidate gene for schizophrenia." ], "offsets": [ [ 0, 57 ] ] }, { "id": "72154d9f-0e1c-4963-b8b4-48e96294af8a", "type": "abstract", "text": [ "Several studies have suggested that the regulator of G-protein signaling 4 (RGS4) may be a positional and functional candidate gene for schizophrenia. Three single nucleotide polymorphisms (SNP) located at the promoter region (SNP4 and SNP7) and the intron 1 (SNP18) of RGS4 have been verified in different ethnic groups. Positive results have been reported in these SNPs with different numbers of SNP combinatory haplotypes. In this study, these three SNP markers were genotyped in 218 schizophrenia pedigrees of Taiwan (864 individuals) for association analysis. Among these three SNPs, neither SNP4, SNP7, SNP18 has shown significant association with schizophrenia in single locus association analysis, nor any compositions of the three SNP haplotypes has shown significantly associations with the DSM-IV diagnosed schizophrenia. Our results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated from these three SNP markers." ], "offsets": [ [ 58, 1010 ] ] } ]

[ { "id": "a015e458-7bd4-4385-b3e0-8b489e0a5fd8", "type": "Gene", "text": [ "RGS4" ], "offsets": [ [ 14, 18 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "da2b1f8f-467b-4bc5-bbf7-eefa56ebbcfc", "type": "Gene", "text": [ "regulator of G-protein signaling 4" ], "offsets": [ [ 98, 132 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "398e4699-a0d2-4b43-b824-f6dcd0f8001f", "type": "Gene", "text": [ "RGS4" ], "offsets": [ [ 134, 138 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f4417778-b11d-446e-975b-a872dd41b8b7", "type": "Gene", "text": [ "RGS4" ], "offsets": [ [ 328, 332 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "78acb4c6-73db-478c-9506-5135a22f93b2", "type": "Gene", "text": [ "RGS4" ], "offsets": [ [ 923, 927 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "b52dafa2-685c-4e52-9163-5cd0ea1a902c", "type": "title", "text": [ "Distinct patterns of germ-line deletions in MLH1 and MSH2: the implication of Alu repetitive element in the genetic etiology of Lynch syndrome (HNPCC)." ], "offsets": [ [ 0, 151 ] ] }, { "id": "acfb811f-1433-4f2a-bb3f-c60137cf4721", "type": "abstract", "text": [ "A relatively high frequency of germ-line genomic rearrangements in MLH1 and MSH2 has been reported among Lynch Syndrome (HNPCC) patients from different ethnic populations. To investigate the underlying molecular mechanisms, we characterized the DNA breakpoints of 11 germ-line deletions, six for MLH1 and five for MSH2. Distinct deletion patterns were found for the two genes. The five cases of MSH2 deletions result exclusively from intragenic unequal recombination mediated by repetitive Alu sequences. In contrast, five out of the six MLH1 deletions are due to recombinations involving sequences of no significant homology (P=0.015). A detailed analysis of the DNA breakpoints in the two genes, previously characterized by other groups, validated the observation that Alu-mediated unequal recombination is the main type of deletion in MSH2 (n=34), but not in MLH1 (n=21) (P<0.0001). Plotting the distribution of known DNA breakpoints among the introns of the two genes showed that, the highest breakpoint density is co-localized with the highest Alu density. Our study suggests that Alu is a promoting factor for the genomic recombinations in both MLH1 and MSH2, and the local Alu density may be involved in shaping the deletion pattern." ], "offsets": [ [ 152, 1395 ] ] } ]

[ { "id": "231e6e83-fff6-4eb1-bb28-303364da7cbc", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 44, 48 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6465792c-64ec-4155-9ba2-62515a060f26", "type": "Gene", "text": [ "MSH2" ], "offsets": [ [ 53, 57 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c6365cea-a6ea-4afc-9047-4eee019cab92", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 219, 223 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e9ecd3d6-ef39-4f94-b0ea-5e44c813274b", "type": "Gene", "text": [ "MSH2" ], "offsets": [ [ 228, 232 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "48f167b1-cea0-4ea5-b803-44a6068402bf", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 448, 452 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0fe72475-de05-4785-8327-5c26d69e3346", "type": "Gene", "text": [ "MSH2" ], "offsets": [ [ 466, 470 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3a1fc78c-2b43-4591-bfae-aab8d0e7bdaa", "type": "Gene", "text": [ "MSH2" ], "offsets": [ [ 547, 551 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "067b2754-87f0-48a8-8e88-3cc02aa6fb03", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 690, 694 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7d2008ee-e785-405a-b3b4-6a07efcb2a99", "type": "Gene", "text": [ "MSH2" ], "offsets": [ [ 990, 994 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4ebe831c-ebd8-4da1-8ea6-1b5a09f9cca5", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 1014, 1018 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "433d54b8-29fe-4a56-975b-311e39850706", "type": "Gene", "text": [ "MLH1" ], "offsets": [ [ 1306, 1310 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cabc3b67-2f7a-4c1b-8a89-e5fe41c0bc6c", "type": "Gene", "text": [ "MSH2" ], "offsets": [ [ 1315, 1319 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "eb49167f-0005-49ea-9f67-cd02338c08b6", "type": "title", "text": [ "Gene therapy for cystic fibrosis airway disease- is clinical success imminent?" ], "offsets": [ [ 0, 78 ] ] }, { "id": "de155251-c21b-4bc4-ab10-0d5455a2e516", "type": "abstract", "text": [ "Cystic fibrosis (CF) was one of the first inherited disorders for which gene therapy was seriously considered as a realistic option for treatment, and as such, it has long provided a paradigm for gene therapy of inherited diseases. However, despite the cloning of the cystic fibrosis transmembrane conductance regulator gene in 1989, over 15 years later a practical gene therapy for CF has not eventuated. There are a number of reasons for this, and analysis of the specific issues that have delayed the successful development of gene therapy for CF also provides general insights into the practical complexities involved in the development of gene therapy for inherited disorders. The issues which have prevented the application of gene therapy for CF to date include the lack of suitable gene delivery technologies, the complexities of the interactions between the host and vector, the biology of the lung airways, and the nature of the pathology found in individuals with CF. We will discuss the history of CF gene therapy with specific reference to these and other issues that pre-occupy the field at present: namely, the question of what vectors appear to be suitable for airway gene delivery in CF, what cells must be targeted, how airway epithelium defences can be overcome or eluded to allow efficient gene delivery, how to ensure safe and long-term transgene expression and the need to identify relevant surrogate success measures that can be used to assess the outcome of gene therapy in CF patients." ], "offsets": [ [ 79, 1589 ] ] } ]

[ { "id": "57cbe95a-0d97-4429-a334-2c546b6a331e", "type": "Gene", "text": [ "cystic fibrosis transmembrane conductance regulator" ], "offsets": [ [ 347, 398 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c6e2a6d1-49d5-476a-8082-bb54e9c54ce3", "type": "FamilyName", "text": [ "CF" ], "offsets": [ [ 1089, 1091 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "fe737c49-62d0-45d1-b709-3238ccb54c17", "type": "title", "text": [ "Mutations responsible for Larsen syndrome cluster in the FLNB protein." ], "offsets": [ [ 0, 70 ] ] }, { "id": "a6cf951d-17f7-48e1-8b92-99855d910395", "type": "abstract", "text": [ "BACKGROUND: A gene for Larsen syndrome was recently described, and mutations were reported in five cases. OBJECTIVE: To test whether mutations in this gene, FLNB, could explain the disease in our independent collection of sporadic and dominant Larsen syndrome cases; and to test whether mutations occurred in a non-random pattern. RESULTS: Missense mutations were found in each of five cases. Four of the five were new; one was reported in a sporadic case in the original Larsen syndrome study of five cases. All mutations from the two studies were compiled. Clustered mutations were observed within three filamin B protein domains: the calponin homology 2 domain, repeat 14, and repeat 15. This suggested that as few as five (of the total of 46) coding exons of FLNB could be screened to detect Larsen syndrome mutations. Four of these exons were screened in a sixth (sporadic) case and a previously reported G1691S substitution mutation detected. CONCLUSIONS: Mutations in FLNB may be responsible for all cases of Larsen syndrome. They appear to occur in specific functional domains of the filamin B protein. This should simplify diagnostic screening of the FLNB gene. Analyses in larger patient series are warranted to quantify this. The study confirmed the extreme variability in clinical presentation and the presence of unaffected carriers. A molecular screen would be valuable for diagnosis and genetic counselling." ], "offsets": [ [ 71, 1493 ] ] } ]

[ { "id": "df50d4a1-d6ea-46e2-8b26-a210a02e5b3f", "type": "Gene", "text": [ "FLNB" ], "offsets": [ [ 57, 61 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "72d93df0-dfab-4fb7-9a79-ac27ef2a0720", "type": "Gene", "text": [ "FLNB" ], "offsets": [ [ 228, 232 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0157ed05-defd-4e27-b84a-681690f8afcb", "type": "Gene", "text": [ "filamin B" ], "offsets": [ [ 677, 686 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a067ab66-5295-4b3e-8490-e8791502dfa8", "type": "DomainMotif", "text": [ "calponin homology 2 domain" ], "offsets": [ [ 708, 734 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "505447b7-66db-4c3c-a8eb-22c643d62f6a", "type": "Gene", "text": [ "FLNB" ], "offsets": [ [ 834, 838 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0fec709d-fa5d-4a8d-be17-1fcd2ae4f259", "type": "Gene", "text": [ "FLNB" ], "offsets": [ [ 1046, 1050 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9fcbf8c1-0061-4acd-ad20-ffe1b7f03c12", "type": "Gene", "text": [ "filamin B" ], "offsets": [ [ 1163, 1172 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "18ee6fcc-4d47-4f07-9a94-aa57bb22443e", "type": "Gene", "text": [ "FLNB" ], "offsets": [ [ 1231, 1235 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c7f30308-7978-4fdf-8f27-1c7b288c5a3e", "type": "title", "text": [ "Array-based comparative genomic hybridization facilitates identification of breakpoints of a novel der(1)t(1;18)(p36.3;q23)dn in a child presenting with mental retardation." ], "offsets": [ [ 0, 172 ] ] }, { "id": "9a513ab4-f6c5-4b30-9dd8-17f957a49abd", "type": "abstract", "text": [ "Monosomy of distal 1p36 represents the most common terminal deletion in humans and results in one of the most frequently diagnosed mental retardation syndromes. This deletion is considered a contiguous gene deletion syndrome, and has been shown to vary in deletion sizes that contribute to the spectrum of phenotypic anomalies seen in patients with monosomy 1p36. We report on an 8-year-old female with characteristics of the monosomy 1p36 syndrome who demonstrated a novel der(1)t(1;18)(p36.3;q23). Initial G-banded karyotype analysis revealed a deleted chromosome 1, with a breakpoint within 1p36.3. Subsequent FISH and array-based comparative genomic hybridization not only confirmed and partially characterized the deletion of chromosome 1p36.3, but also uncovered distal trisomy for 18q23. In this patient, the duplicated 18q23 is translocated onto the deleted 1p36.3 region, suggesting telomere capture. Molecular characterization of this novel der(1)t(1;18)(p36.3;q23), guided by our clinical array-comparative genomic hybridization, demonstrated a 3.2 Mb terminal deletion of chromosome 1p36.3 and a 200 kb duplication of 18q23 onto the deleted 1p36.3, presumably stabilizing the deleted chromosome 1. DNA sequence analysis around the breakpoints demonstrated no homology, and therefore this telomere capture of distal 18q is apparently the result of a non-homologous recombination. Partial trisomy for 18q23 has not been previously reported. The importance of mapping the breakpoints of all balanced and unbalanced translocations found in the clinical laboratory, when phenotypic abnormalities are found, is discussed." ], "offsets": [ [ 173, 1800 ] ] } ]

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[ { "id": "690bb9c1-ca6a-4330-9170-2d7d4316f8ad", "type": "title", "text": [ "Clinical and molecular characterization of individuals with 18p deletion: a genotype-phenotype correlation." ], "offsets": [ [ 0, 107 ] ] }, { "id": "76216c3c-a440-4cbd-a1f7-5598222c119c", "type": "abstract", "text": [ "The deletion 18p syndrome is one of the most common chromosome abnormalities. The medical problems are mental and postnatal growth retardation, and sometimes malformations of the heart and brain. The individuals have some typical features, which might be easy to overlook and which are: ptosis, strabismus, hypertelorism, broad flat nose, micrognathia, big and low set ears. The aims of present study were to clinically and molecularly characterize the syndrome further in seven subjects with de novo 18p deletions and to perform genotype-phenotype correlation. All seven subjects had terminal deletions and no interstitial deletion was observed with subtelomeric FISH analyses. To define the extent of the 18p deletions and the parental origin of the deletion microsatellite- and FISH analyses were performed on genomic DNA and on lymphoblastoid cell lines of the study participants. Totally 19 chromosomes, 18 specific polymorphic microsatellite markers, and 5 BAC clones were used. The results revealed that the deletions were located in the centromeric region at 18p11.1 in four of the seven subjects. In the remaining three the breakpoints were located distal to 18p11.1 (18p11.21-p11.22). Four of the individuals had a paternal and three a maternal origin of the deletion. Genotype-phenotype correlation of the seven subjects suggests a correlation between the extent of the deleted region and the mental development. All the four children with a deletion in the centromeric region at 18p11.1 had a mental retardation (MR). Two of the three children with a more distal breakpoint (distal 18p11.21) had a normal mental development and one had a border-line mental retardation. There might be a critical region for the mental retardation located between 18p11.1 and 18p11.21. The children with a breakpoint at 18p11.1 had all a broad face, which was observed in only one of those with a more distal breakpoint, otherwise no genotype-phenotype correlation of the features was observed." ], "offsets": [ [ 108, 2096 ] ] } ]

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[ { "id": "e70c2d0e-d254-4571-ad45-c7289550a5f9", "type": "title", "text": [ "Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region." ], "offsets": [ [ 0, 131 ] ] }, { "id": "ca79bf23-7c30-4c6d-8ee5-fe563a2ef7c7", "type": "abstract", "text": [ "Split-hand/split-foot malformation (SHFM, also called ectrodactyly) is a clinically variable and genetically heterogeneous group of limb malformations. Several SHFM loci have been mapped, including SHFM1 (7q21), SHFM2 (Xq26), SHFM3 (10q24), SHFM4 (3q27) and SHFM5 (2q31). To date, mutations in a gene (TP63) have only been identified for SHFM4. SHFM3 has been shown by pulsed-field gel electrophoresis to be caused by an approximately 500 kb DNA rearrangement at 10q24. This region contains a number of candidate genes for SHFM3, though which gene(s) is (are) involved in the pathogenesis of SHFM3 is not known. Our aim in this study was to improve the diagnosis of SHFM3, and to begin to understand which genes are involved in SHFM3. Here we show, using two different techniques, FISH and quantitative PCR that SHFM3 is caused by a minimal 325 kb duplication containing only two genes (BTRC and POLL). The data presented provide improved methods for diagnosis and begin to elucidate the pathogenic mechanism of SHFM3. Expression analysis of 13 candidate genes within and flanking the duplicated region shows that BTRC (present in three copies) and SUFU (present in two copies) are overexpressed in SHFM3 patients compared to controls. Our data suggest that SHFM3 may be caused by overexpression of BTRC and SUFU, both of which are involved in beta-catenin signalling." ], "offsets": [ [ 132, 1500 ] ] } ]

[ { "id": "79bd5040-b62d-4604-9f45-08cb0212fc46", "type": "Gene", "text": [ "Split-hand/split-foot malformation 3" ], "offsets": [ [ 0, 36 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9c291ef0-b43e-48f1-a62b-6e0bff844c3b", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 38, 43 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1eb8ee94-2ad6-4ab9-a53b-3ef8f8066b82", "type": "FamilyName", "text": [ "Split-hand/split-foot malformation" ], "offsets": [ [ 132, 166 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f24cf4df-fa50-462d-810f-16f3d70faa10", "type": "FamilyName", "text": [ "SHFM" ], "offsets": [ [ 168, 172 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "279c7b89-4f41-40da-9e5f-a183da447fec", "type": "FamilyName", "text": [ "SHFM" ], "offsets": [ [ 292, 296 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "be69280c-76ca-4b92-bca3-c1f1768af3ea", "type": "Gene", "text": [ "SHFM1" ], "offsets": [ [ 330, 335 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "456a4e0b-151c-49ba-bdd5-ae9d42577d0a", "type": "Gene", "text": [ "SHFM2" ], "offsets": [ [ 344, 349 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9e99b1ce-f023-434c-8fa9-8f6993b510ee", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 358, 363 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c4a69097-4ae3-40ba-b79b-51f7bec74ab8", "type": "Gene", "text": [ "SHFM4" ], "offsets": [ [ 373, 378 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8188171e-df71-41e2-933f-f9d501d99e88", "type": "Gene", "text": [ "SHFM5" ], "offsets": [ [ 390, 395 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2c5eaec7-4ac6-4ed2-86c0-09a8702cfed8", "type": "Gene", "text": [ "TP63" ], "offsets": [ [ 434, 438 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cade65f7-fd77-4f1f-8113-510d77648f4a", "type": "Gene", "text": [ "SHFM4" ], "offsets": [ [ 470, 475 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "63f12262-444a-40d7-a69b-c62f71c3f7db", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 477, 482 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8e3f101b-9810-4182-bc54-b1ca70afacfa", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 655, 660 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c8e27829-6d70-41af-b25f-082f8da8fae5", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 724, 729 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "08c3beb9-a807-4979-9c18-1daa94e04637", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 798, 803 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1f5fe8eb-685f-4121-9843-f3ba8120a125", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 860, 865 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a4cfdaa4-d8c4-43fa-93fa-cee56fa7ffa4", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 944, 949 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "02725be2-103a-46ba-8465-5c67a308d0ed", "type": "Gene", "text": [ "BTRC" ], "offsets": [ [ 1019, 1023 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6e0023a8-70c3-4093-9776-003132ad8978", "type": "Gene", "text": [ "POLL" ], "offsets": [ [ 1028, 1032 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7c5222db-e19d-4cb3-be66-51f0dc403b1b", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 1144, 1149 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "80ce25b1-514c-4f25-847e-9c81e425c1e7", "type": "Gene", "text": [ "BTRC" ], "offsets": [ [ 1246, 1250 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a1c15ebf-6118-468f-bcc5-4dfc08129f34", "type": "Gene", "text": [ "SUFU" ], "offsets": [ [ 1281, 1285 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "150fa46a-9188-4984-94f5-24c6a3805346", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 1331, 1336 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9c99aafd-80ed-428a-8de2-bcbcf08c33f2", "type": "Gene", "text": [ "SHFM3" ], "offsets": [ [ 1390, 1395 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c0544a27-6c86-4fae-b7ca-eea0aca41366", "type": "Gene", "text": [ "BTRC" ], "offsets": [ [ 1431, 1435 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2442944b-2384-4f37-96c4-ef35d1b9d5e2", "type": "Gene", "text": [ "SUFU" ], "offsets": [ [ 1440, 1444 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2dff9620-0076-4c76-b83f-2d7272c39652", "type": "Gene", "text": [ "beta-catenin" ], "offsets": [ [ 1476, 1488 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "dfcf969d-d785-49e5-90cc-74e38c5c1074", "type": "title", "text": [ "Identification of the nuclear localization motif in the ETV6 (TEL) protein." ], "offsets": [ [ 0, 75 ] ] }, { "id": "4445c851-5780-4ae3-8bca-3e865e55f7df", "type": "abstract", "text": [ "ETV6, or Translocation-Ets-Leukemia (TEL), is an ETS family transcriptional repressor that is essential for establishing hematopoiesis in neonatal bone marrow, and is frequently a target of chromosomal translocations in human cancer. ETV6 is predominantly a nuclear phosphoprotein that represses transcription by binding directly to the promoters of target genes. The nuclear localization mechanism of ETV6, however, is not well understood. In this report, we provide evidence that a nuclear localization signal (NLS) exists in the C-terminal region of ETV6. ETV6 proteins with mutations outside of amino acids 332-452 localize to the nucleus, whereas proteins with mutations within amino acids 332-452 remain in the cytoplasm. Furthermore, when a fragment of ETV6 comprised of amino acids 332-452 was fused to cytoplasmic beta-galactosidase protein, the fusion protein was able to enter the nucleus. These results strongly indicate that residues 332-452 mediate nuclear localization of ETV6." ], "offsets": [ [ 76, 1068 ] ] } ]

[ { "id": "511b7070-d94a-4c54-b747-35fc0b80b099", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 56, 60 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ad61bf2f-950e-4831-98a3-4ef1f640e5f0", "type": "Gene", "text": [ "TEL" ], "offsets": [ [ 62, 65 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4e6b9e30-d788-4d30-ae1b-e203cc246430", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 76, 80 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7e3f733a-d69b-41aa-904c-e2ff54906082", "type": "Gene", "text": [ "Translocation-Ets-Leukemia" ], "offsets": [ [ 85, 111 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ec26a43f-c647-49be-8410-a9ffad2c8a1d", "type": "Gene", "text": [ "TEL" ], "offsets": [ [ 113, 116 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "caebbbe0-3501-44a9-ad05-ef04729a83c1", "type": "FamilyName", "text": [ "ETS family transcriptional repressor" ], "offsets": [ [ 125, 161 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b2fadc24-93a9-45e4-a2b2-29314396edec", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 310, 314 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "99635fad-4f4a-47c1-b295-90a971f1b6bc", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 478, 482 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a88dab0e-e233-4524-aa0e-490c58c43930", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 629, 633 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2f662457-c1b6-4047-8988-88f5403a9e7e", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 635, 639 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e6b41edd-128d-43f6-a641-5ea64da33030", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 836, 840 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "91128d63-3992-4221-9477-fe2c6301414d", "type": "Gene", "text": [ "beta-galactosidase" ], "offsets": [ [ 899, 917 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a9b16281-78db-4ad8-935f-ec760387f67b", "type": "Gene", "text": [ "ETV6" ], "offsets": [ [ 1063, 1067 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c0b1e402-731e-4ae3-8267-e3eb68d85be3", "type": "title", "text": [ "McArdle disease: the mutation spectrum of PYGM in a large Italian cohort." ], "offsets": [ [ 0, 73 ] ] }, { "id": "a09b6fd9-a4f2-4808-8fd7-2e5d260c6164", "type": "abstract", "text": [ "Deficiency of the muscle isozyme of glycogen phosphorylase is causative of McArdle disease or Glycogen storage disease type V (GSD-V), the most common autosomal recessive disorder of glycogen metabolism. The typical clinical presentation is characterized by exercise intolerance with cramps, and recurrent myoglobinuria. To date, 46 mutations in the PYGM gene have been detected in GSD-V patients. We report the mutational spectrum in 68 Italian patients. We identified 30 different mutations in the PYGM gene, including 19 mutations that have not been reported previously. The novel mutations include: eight missense mutations (c.475G>A, p.G159R; c.689C>G, p.P230R; c.1094C>T, p.A365E; c.1151C>A, p.A384D; c.1182C>T, p.R428C; c.1471C>T, p.R491C; c.2444A>C, p.D815A; c.2477G>C, p.W826S), two nonsense mutations (c.1475G>A, p.W492X; c.1627A>T, p.K543X), five splice site mutations (c.855 +1G>C; c.1092 +1G>A; c. 1093-1G>T; c.1239 +1G>A; c.2380 +1G>A), and four deletions (c.715_717delGTC, p.V239del; c.304delA, p.N102DfsX4; c.1970_2177del, p.V657_G726; c.2113_2114delGG, p.G705RfsX16). Whereas we confirmed lack of direct correlation between the clinical phenotype and the genotype, we also found that the so-called 'common mutation' (p.R50X) accounted for about 43% of alleles in our cohort and that no population-related mutations are clearly identified in Italian patients." ], "offsets": [ [ 74, 1504 ] ] } ]

[ { "id": "7516c441-486c-4821-bb5a-b6947b833386", "type": "Gene", "text": [ "PYGM" ], "offsets": [ [ 42, 46 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5fc0fd39-28bd-49f4-90c5-dbba10e8d3f9", "type": "Gene", "text": [ "PYGM" ], "offsets": [ [ 424, 428 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2000bb90-93d6-4d75-bab5-1eedef322998", "type": "Gene", "text": [ "PYGM" ], "offsets": [ [ 574, 578 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "dd9ddd5f-4d05-49be-9213-3ecd6feb9006", "type": "title", "text": [ "A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population." ], "offsets": [ [ 0, 138 ] ] }, { "id": "b9e32af9-e8ec-49e8-ae7f-1cba90780d77", "type": "abstract", "text": [ "Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression." ], "offsets": [ [ 139, 1781 ] ] } ]

[ { "id": "77180205-0247-470b-a760-461694820456", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 45, 49 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "096e0cd9-3cdc-488e-90e7-2b1aeabf07d0", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 254, 258 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b27b0ad6-ab33-4f58-a8af-a12dfa9ef4ab", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 360, 364 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b065905-5c1d-46e8-903d-aecc01e8a140", "type": "Gene", "text": [ "interleukin 1 beta" ], "offsets": [ [ 416, 434 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1e9042e1-b816-483e-bcab-869eae66d944", "type": "Gene", "text": [ "IL1beta" ], "offsets": [ [ 436, 443 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fe95850f-d461-412c-8f48-a821db1919c5", "type": "Gene", "text": [ "nuclear factor of kappa B" ], "offsets": [ [ 462, 487 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "dd330d9d-f174-4824-83dd-11d559efd3a6", "type": "Gene", "text": [ "NFkappaB" ], "offsets": [ [ 489, 497 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "771703e9-d27f-4e9d-b1ad-9ddf3aa86da6", "type": "Gene", "text": [ "FS-7 cell-associated cell surface antigen" ], "offsets": [ [ 584, 625 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "de636450-0493-4c66-9f7a-0a04d5186dc5", "type": "Gene", "text": [ "FAS" ], "offsets": [ [ 627, 630 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "caba59b9-32d1-4fab-b5ad-7dc8dfcb7e11", "type": "Gene", "text": [ "NFkappaB" ], "offsets": [ [ 727, 735 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "20754d52-dbbc-49b4-acda-91ed00e1d274", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 849, 853 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f5a30ca2-a5f7-49f5-95c1-83e21321c9e5", "type": "Gene", "text": [ "FAS" ], "offsets": [ [ 867, 870 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "efa7cc7f-3f54-406d-8e8d-341eb0940fdc", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1191, 1195 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "440281ce-3fc3-4dee-b098-7faa54a7ec6c", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1249, 1253 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "819198cf-da5d-4c6b-b40c-0e662f7fcc53", "type": "Gene", "text": [ "FAS" ], "offsets": [ [ 1267, 1270 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d6ad2e1b-24d3-461d-9388-48b1912ae7f0", "type": "Gene", "text": [ "FAS" ], "offsets": [ [ 1360, 1363 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d67e02cb-cf57-49e1-9c3b-f685df70d557", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1455, 1459 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ed17ea8b-a4cc-48ce-ad15-116bcf25b2d3", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1469, 1473 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "11ed1171-8708-4289-a30c-f51873cb45f7", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1617, 1621 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f412b8c4-e0ee-4ce5-bf02-775e87a4bc1b", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1631, 1635 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "83cf0a71-11c8-40ea-8937-484a09cf6e5a", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1716, 1720 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "92e59c70-b84e-4c38-96b2-0492fe6c6eeb", "type": "Gene", "text": [ "IL1B" ], "offsets": [ [ 1730, 1734 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c1873a1c-bfd2-4d1f-bb54-154d3204af95", "type": "title", "text": [ "A two base pair deletion in the PQBP1 gene is associated with microphthalmia, microcephaly, and mental retardation." ], "offsets": [ [ 0, 115 ] ] }, { "id": "82a53b97-9440-41e0-afcc-2e0bdace1c59", "type": "abstract", "text": [ "X-linked mental retardation has been traditionally divided into syndromic (S-XLMR) and non-syndromic forms (NS-XLMR), although the borderlines between these phenotypes begin to vanish and mutations in a single gene, for example PQBP1, can cause S-XLMR as well as NS-XLMR. Here, we report two maternal cousins with an apparently X-linked phenotype of mental retardation (MR), microphthalmia, choroid coloboma, microcephaly, renal hypoplasia, and spastic paraplegia. By multipoint linkage analysis with markers spanning the entire X-chromosome we mapped the disease locus to a 28-Mb interval between Xp11.4 and Xq12, including the BCOR gene. A missense mutation in BCOR was described in a family with Lenz microphthalmia syndrome, a phenotype showing substantial overlapping features with that described in the two cousins. However, no mutation in the BCOR gene was found in both patients. Subsequent mutation analysis of PQBP1, located within the delineated linkage interval in Xp11.23, revealed a 2-bp deletion, c.461_462delAG, that cosegregated with the disease. Notably, the same mutation is associated with the Hamel cerebropalatocardiac syndrome, another form of S-XLMR. Haplotype analysis suggests a germline mosaicism of the 2-bp deletion in the maternal grandmother of both affected individuals. In summary, our findings demonstrate for the first time that mutations in PQBP1 are associated with an S-XLMR phenotype including microphthalmia, thereby further extending the clinical spectrum of phenotypes associated with PQBP1 mutations." ], "offsets": [ [ 116, 1659 ] ] } ]

[ { "id": "556c9ee6-6dd3-4f6e-a8de-e102c4280a0a", "type": "Gene", "text": [ "PQBP1" ], "offsets": [ [ 32, 37 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ba16225d-8bb9-4c09-854f-e72ad1e4cf4c", "type": "Gene", "text": [ "PQBP1" ], "offsets": [ [ 344, 349 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9f38ecce-0ca6-41f5-91db-825c1538a90a", "type": "Gene", "text": [ "BCOR" ], "offsets": [ [ 745, 749 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2574aa25-fc48-4d46-9eb6-84ac73d267ca", "type": "Gene", "text": [ "BCOR" ], "offsets": [ [ 779, 783 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a4e716bd-08b7-4f2a-9ecb-58061035cbcc", "type": "Gene", "text": [ "BCOR" ], "offsets": [ [ 966, 970 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eefbb69b-1424-4136-bc31-495787c95209", "type": "Gene", "text": [ "PQBP1" ], "offsets": [ [ 1036, 1041 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d380c23a-370e-49a5-be68-fa21829eb5db", "type": "Gene", "text": [ "PQBP1" ], "offsets": [ [ 1493, 1498 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "92fe9cd3-41b3-41d3-83d1-6b70e9d2558b", "type": "Gene", "text": [ "PQBP1" ], "offsets": [ [ 1643, 1648 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "38862561-e2de-4db8-92c4-e5b7298a52be", "type": "title", "text": [ "A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutations." ], "offsets": [ [ 0, 119 ] ] }, { "id": "6fd3b77a-b381-49e4-a010-66efd59dbacf", "type": "abstract", "text": [ "Renal tubular dysgenesis (RTD) is a developmental abnormality of the renal proximal tubules found in patients with Potter syndrome. We report a female newborn with RTD who has survived for more than 18 months. Infusions of fresh frozen plasma (FFP) in the early neonatal period were effective in raising and maintaining her blood pressure. Peritoneal dialysis was required until the appearance of spontaneous urination at 29 days after birth. Histopathological examinations of the kidney revealed dilated renal tubular lumina and foamy columnar epithelial cells in the renal tubules. Endocrinological studies showed a discrepancy between low plasma renin activity (<0.1 ng/ml/hr) and high active renin concentration (135,000 pg/ml), suggesting an aberration in the renin substrate, angiotensinogen. Direct sequencing analysis revealed two novel mutations in the coding region of the angiotensinogen gene (AGT): a nonsense mutation in exon 2 (c.604C > T) and a frameshift deletion at nucleotide 1290 in exon 5 (c.1290delT). The mutations were in the compound heterozygous state, because each parent had each mutation. These findings suggest that angiotensinogen deficiency is one of the causes of RTD. A treatment of the condition with FFP may help to promote long survival." ], "offsets": [ [ 120, 1399 ] ] } ]

[ { "id": "eb24cb2b-7839-462a-a8e6-4bc2b8438a69", "type": "Gene", "text": [ "angiotensinogen" ], "offsets": [ [ 88, 103 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c26db7cb-94e4-4b76-bd8f-87f363576b88", "type": "Gene", "text": [ "renin" ], "offsets": [ [ 769, 774 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "952255f4-e949-4a40-8fef-406c728527c6", "type": "Gene", "text": [ "renin" ], "offsets": [ [ 819, 824 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bf541aab-7695-4a5d-92c6-05780fe77c93", "type": "Gene", "text": [ "renin" ], "offsets": [ [ 888, 893 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "38b62444-ae41-4760-b9f6-c2f691e41551", "type": "Gene", "text": [ "angiotensinogen" ], "offsets": [ [ 905, 920 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "223bfcaf-ed56-4386-ad06-6fee62bb92c5", "type": "Gene", "text": [ "angiotensinogen" ], "offsets": [ [ 1006, 1021 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4801ddcd-dba5-4140-988e-eae26f943a16", "type": "Gene", "text": [ "AGT" ], "offsets": [ [ 1028, 1031 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2ef2eb1e-e411-4172-8edc-042c4b94989e", "type": "Gene", "text": [ "angiotensinogen" ], "offsets": [ [ 1271, 1286 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "b33fc71f-ae6c-4660-b38e-07367de690e8", "type": "title", "text": [ "Functional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophrenia." ], "offsets": [ [ 0, 110 ] ] }, { "id": "bd3bcaef-997b-44fa-909f-f20a893e810e", "type": "abstract", "text": [ "The chitinase 3-like 1 gene (CHI3L1) is abnormally expressed in the hippocampus of subjects with schizophrenia and may be involved in the cellular response to various environmental events that are reported to increase the risk of schizophrenia. Here, we provide evidence that the functional variants at the CHI3L1 locus influence the genetic risk of schizophrenia. First, using case-control and transmission/disequilibrium-test (TDT) methodologies, we detected a significant association between schizophrenia and haplotypes within the promoter region of CHI3L1 in two independent cohorts of Chinese individuals. Second, the at-risk CCC haplotype (P=.00058 and .0018 in case-control and TDT studies, respectively) revealed lower transcriptional activity (P=2.2 x 10(-7)) and was associated with lower expression (P=3.1 x 10(-5)) compared with neutral and protective haplotypes. Third, we found that an allele of SNP4 (rs4950928), the tagging SNP of CCC, impaired the MYC/MAX-regulated transcriptional activation of CHI3L1 by altering the transcriptional-factor consensus sequences, and this may be responsible for the decreased expression of the CCC haplotype. In contrast, the protective TTG haplotype was associated with a high level of CHI3L1 expression. Our findings identify CHI3L1 as a potential schizophrenia-susceptibility gene and suggest that the genes involved in the biological response to adverse environmental conditions are likely to play roles in the predisposition to schizophrenia." ], "offsets": [ [ 111, 1609 ] ] } ]

[ { "id": "733b1bda-0376-4c4a-9362-35094b8c65d1", "type": "Gene", "text": [ "Chitinase 3-like 1" ], "offsets": [ [ 46, 64 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "31c33258-d5ad-4a43-a546-4e0c6d1e1c4a", "type": "Gene", "text": [ "CHI3L1" ], "offsets": [ [ 66, 72 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a4f98aa4-e158-495e-a6a5-5da6f3b06937", "type": "Gene", "text": [ "chitinase 3-like 1" ], "offsets": [ [ 115, 133 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9c96ffdc-aacb-4449-aa36-6a18b1358430", "type": "Gene", "text": [ "CHI3L1" ], "offsets": [ [ 140, 146 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "9034e126-2585-48a2-a80c-940b46474ff1", "type": "Gene", "text": [ "CHI3L1" ], "offsets": [ [ 418, 424 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "fd447785-ccc0-42b5-afb1-c0c537134498", "type": "Gene", "text": [ "CHI3L1" ], "offsets": [ [ 665, 671 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "26479396-766a-4f73-a8f8-f4b22717d2a6", "type": "Gene", "text": [ "MYC" ], "offsets": [ [ 1077, 1080 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f957f6d2-878f-4f44-879d-acb04bf15900", "type": "Gene", "text": [ "MAX" ], "offsets": [ [ 1081, 1084 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "36abc1d9-0520-4046-bede-bd82885157a7", "type": "Gene", "text": [ "CHI3L1" ], "offsets": [ [ 1125, 1131 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d7d05331-9242-45dc-8619-bc2253d79e06", "type": "Gene", "text": [ "CHI3L1" ], "offsets": [ [ 1349, 1355 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d527a2c2-80a3-4fd8-a692-c3d03e2334b7", "type": "Gene", "text": [ "CHI3L1" ], "offsets": [ [ 1390, 1396 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "68fc16f4-b914-458b-b106-ae65e0f869fd", "type": "FamilyName", "text": [ "potential schizophrenia-susceptibility gene" ], "offsets": [ [ 1402, 1445 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "9589fc95-1d7f-41fd-8f02-a878d3f383b8", "type": "title", "text": [ "Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants." ], "offsets": [ [ 0, 98 ] ] }, { "id": "7e109882-bf86-47e9-9428-269b0504d9a7", "type": "abstract", "text": [ "Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal NAT2 and CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set, NAT2 continued to show significant overtransmission of an allele to the fetus, with a final P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a GSTT1-null deletion, seen in both the Danish (P=.03) and Iowan (P=.002) studies, with a Fisher's combined P value of <.001, which remained significant after correction for multiple comparisons. Gene-expression analysis demonstrated expression of GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care." ], "offsets": [ [ 99, 1786 ] ] } ]

[ { "id": "a245d890-07e7-48d1-8565-7fe0c52469c6", "type": "FamilyName", "text": [ "detoxification-gene" ], "offsets": [ [ 69, 88 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0cabc8d0-2592-4d08-82c6-7a5f91a6855e", "type": "Gene", "text": [ "NAT2" ], "offsets": [ [ 927, 931 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0a5922f9-5542-47d3-be5c-88b2faa51644", "type": "Gene", "text": [ "CYP1A1" ], "offsets": [ [ 936, 942 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "57eb1818-0923-4e77-b083-e89408b94680", "type": "Gene", "text": [ "NAT2" ], "offsets": [ [ 1035, 1039 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "93e2f721-b941-4aa5-9411-c21a376b92d6", "type": "Gene", "text": [ "GSTT1" ], "offsets": [ [ 1223, 1228 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5e03079a-8515-47fb-a1de-fcecd4f2d385", "type": "Gene", "text": [ "GSTT1" ], "offsets": [ [ 1477, 1482 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c4324307-0812-482c-9976-ac277b75e2fb", "type": "title", "text": [ "Families with the risk allele of DISC1 reveal a link between schizophrenia and another component of the same molecular pathway, NDE1." ], "offsets": [ [ 0, 133 ] ] }, { "id": "ff902d9e-3120-4262-8dc6-b789c7b72310", "type": "abstract", "text": [ "We have previously reported a robust association between an allelic haplotype of 'Disrupted in Schizophrenia 1' (DISC1) and schizophrenia in a nationwide collection of Finnish schizophrenia families. This specific DISC1 allele was later identified to associate with visual working memory, selectively in males. DISC1 association to schizophrenia has since been replicated in multiple independent study samples from different populations. In this study, we conditioned our sample of Finnish families for the presence of the Finnish tentative risk allele for DISC1 and re-analyzed our genome-wide scan data of 443 markers on the basis of this stratification. Two additional loci displayed an evidence of linkage (LOD > 3) and included a locus on 16p13, proximal to the gene encoding NDE1, which has been shown to biologically interact with DISC1. Although none of the observed linkages remained significant after multiple test correction through simulation, further analysis of NDE1 revealed an association between a tag-haplotype and schizophrenia (P = 0.00046) specific to females, which proved to be significant (P = 0.011) after multiple test correction. Our finding would support the concept that initial gene findings in multifactorial diseases will assist in the identification of other components of complex genetic etiology. Notably, this and other converging lines of evidence underline the importance of DISC1-related functional pathways in the etiology of schizophrenia." ], "offsets": [ [ 134, 1627 ] ] } ]

[ { "id": "fac6bf6b-d3d4-435f-aa56-4c26a22afdc8", "type": "Gene", "text": [ "DISC1" ], "offsets": [ [ 33, 38 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "906e8482-072c-4da6-9470-b10d5d853960", "type": "Gene", "text": [ "NDE1" ], "offsets": [ [ 128, 132 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b5eaec0-05c2-429a-9a86-9374ba7bf5c6", "type": "Gene", "text": [ "Disrupted in Schizophrenia 1" ], "offsets": [ [ 221, 249 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "93ed3631-4161-437f-9833-1c6a5b5bfa69", "type": "Gene", "text": [ "DISC1" ], "offsets": [ [ 261, 266 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4bf1cf99-2146-412c-a97f-72e1f0bf33f2", "type": "Gene", "text": [ "DISC1" ], "offsets": [ [ 358, 363 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7abf0758-2611-4d53-acf9-089a7bc22c37", "type": "Gene", "text": [ "DISC1" ], "offsets": [ [ 455, 460 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "82182c08-ee25-4567-9c23-e64c20e79367", "type": "Gene", "text": [ "DISC1" ], "offsets": [ [ 701, 706 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8cf4211e-560f-45c3-9b4e-5e9011f1eb79", "type": "Gene", "text": [ "NDE1" ], "offsets": [ [ 928, 932 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2e51564b-1f7b-47c1-bc99-3d6c2c341a15", "type": "Gene", "text": [ "DISC1" ], "offsets": [ [ 985, 990 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "519876d1-2f38-478f-828c-edd32829d0bb", "type": "Gene", "text": [ "NDE1" ], "offsets": [ [ 1123, 1127 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0070e4bc-6a9e-4b28-8148-0f2017dbf856", "type": "Gene", "text": [ "DISC1" ], "offsets": [ [ 1560, 1565 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "f7bbdc8a-c7cf-4dc4-ad2a-0dbc39d53830", "type": "title", "text": [ "Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region." ], "offsets": [ [ 0, 128 ] ] }, { "id": "8a0bb180-d0da-4db0-8406-952b1e62d1d8", "type": "abstract", "text": [ "Townes-Brocks syndrome (TBS) is an autosomal dominant malformation syndrome characterized by renal, anal, ear, and thumb anomalies caused by SALL1 mutations. To date, 36 SALL1 mutations have been described in TBS patients. All but three of those, namely p.R276X, p.S372X, and c.1404dupG, have been found only in single families thereby preventing phenotype-genotype correlations. Here we present 20 novel mutations (12 short deletions, five short duplications, three nonsense mutations) in 20 unrelated families. We delineate the phenotypes and report previously unknown ocular manifestations, i.e. congenital cataracts with unilateral microphthalmia. We show that 46 out of the now 56 SALL1 mutations are located between the coding regions for the glutamine-rich domain mediating SALL protein interactions and 65 bp 3' of the coding region for the first double zinc finger domain, narrowing the SALL1 mutational hotspot region to a stretch of 802 bp within exon 2. Of note, only two SALL1 mutations would result in truncated proteins without the glutamine-rich domain, one of which is reported here. The latter is associated with anal, ear, hand, and renal manifestations, indicating that the glutamine-rich domain is not required for typical TBS." ], "offsets": [ [ 129, 1382 ] ] } ]

[ { "id": "aed13a68-4ab0-4a61-a876-ed6058228727", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 37, 42 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4b595ac4-af77-4bc8-adb9-70438e1342ef", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 106, 111 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2dc17728-5602-42c4-8f4a-ee7b383a6a31", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 270, 275 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3293bbbf-04c2-46f0-b477-d7ba87c4b86d", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 299, 304 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b6a6f5d3-4e72-460d-9d40-4835fca6b5b0", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 815, 820 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7d55c318-7898-4985-916e-7e96e81c1f9a", "type": "DomainMotif", "text": [ "glutamine-rich domain" ], "offsets": [ [ 878, 899 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "229e01fa-8b60-4f5c-b4eb-f6c62a76c3a8", "type": "FamilyName", "text": [ "SALL" ], "offsets": [ [ 910, 914 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a419e0ac-2a5a-4674-953d-01784d5a1889", "type": "DomainMotif", "text": [ "double zinc finger domain" ], "offsets": [ [ 989, 1014 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "94b456fe-1bb5-455c-ac21-830494959fe3", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 1030, 1035 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b5959e7e-38f8-46d4-a4cf-548d2fe89049", "type": "DomainMotif", "text": [ "mutational hotspot region" ], "offsets": [ [ 1036, 1061 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b5df3891-5102-45ce-a059-3622d0e0d36c", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 1118, 1123 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2dc9d1e7-d0c8-49bc-9529-31a1f6d4a3a2", "type": "DomainMotif", "text": [ "glutamine-rich domain" ], "offsets": [ [ 1181, 1202 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "81b51e72-9589-4667-b602-ed9870764fcb", "type": "DomainMotif", "text": [ "glutamine-rich domain" ], "offsets": [ [ 1328, 1349 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "4ace36ce-0d4e-4d4c-8fb4-44ca8585e39b", "type": "title", "text": [ "A 6Mb deletion in band 2q22 due to a complex chromosome rearrangement associated with severe psychomotor retardation, microcephaly and distinctive dysmorphic facial features." ], "offsets": [ [ 0, 174 ] ] }, { "id": "8d926158-bf6c-4fd4-91ed-272937daf32d", "type": "abstract", "text": [ "High-resolution analyses of complex chromosome rearrangements (CCR) have demonstrated in individuals with abnormal phenotypes that not all seemingly balanced CCRs based on G-banding are completely balanced at breakpoint level. Here we report on an apparently balanced de novo CCR involving chromosomes 2, 3 and 5 present in a 6-month-old girl. She was referred for genetic evaluation because of severe psychomotor retardation, distinctive dysmorphic features and microcephaly. A 1Mb resolution array-CGH analysis of DNA from the patient revealed a deletion of about 6Mb for chromosome 2. FISH analysis showed that the deletion interval found in band 2q22 mapped at the translocation breakpoint, and that the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrome, is located within the deletion interval. To our knowledge this is the first case of a complex chromosomal rearrangement associated with Mowat-Wilson syndrome. Our data illustrate the important role for high-resolution investigation of apparently balanced chromosome rearrangements in patients with unexplained psychomotor retardation and/or other clinical features, and should contribute to our understanding of the mechanisms involved in chromosome rearrangement." ], "offsets": [ [ 175, 1420 ] ] } ]

[ { "id": "0aa37b97-69b4-4e2d-a6d3-0a5a3a11b1d6", "type": "Gene", "text": [ "ZFHX1B" ], "offsets": [ [ 883, 889 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "b46d7a02-f6e8-42e5-ba73-16df642b7664", "type": "title", "text": [ "Overexpression of DNA polymerase beta results in an increased rate of frameshift mutations during base excision repair." ], "offsets": [ [ 0, 119 ] ] }, { "id": "eb7da80a-e94e-43ac-9449-3c2d33ef3ce9", "type": "abstract", "text": [ "DNA polymerase beta (Pol beta) is important for the base excision repair (BER) pathway. Overexpression of Pol beta is frequently found in cancer cells and is thought to be associated with tumorigenesis. In this study, we examined BER fidelity in extracts derived from a human lymphoblastoid cell line that over expresses Pol beta compared to normal control cells. Using an in vitro mutagenesis assay, we found an increased rate of frameshift mutations arising during DNA repair in whole-cell extracts derived from the Pol beta-overexpressing cells. We demonstrate that the addition of excess Pol beta to a control cell extract enhances the mutagenic potential of the extract. Furthermore, using cell extracts and purified Pol beta, we demonstrate that the mechanism of frameshift formation involves slippage of Pol beta during the one-nucleotide gap-filling step of BER and that this slippage is fixed by strand-displacement synthesis stimulated by an excess of Pol beta." ], "offsets": [ [ 120, 1091 ] ] } ]

[ { "id": "b4525546-6b96-4c6f-95bd-2a391f5f3ba3", "type": "Gene", "text": [ "DNA polymerase beta" ], "offsets": [ [ 18, 37 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f5b7d0e2-d192-4878-9f8c-a44eb37fbaee", "type": "Gene", "text": [ "DNA polymerase beta" ], "offsets": [ [ 120, 139 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cc532d02-801b-498d-8a2d-1dcf6d7d9ba5", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 141, 149 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "30ae77af-caeb-41e0-9c48-42710a0ecb6f", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 226, 234 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "18ed913b-c5d0-4f24-974a-4e3994fa617a", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 441, 449 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8304fdd1-954f-4057-bb15-d4d3f31c6c74", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 638, 646 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ce218bd5-8566-4fc1-9eb6-cf0607c9adce", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 712, 720 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "938ff7c5-3a23-4cae-a9ea-64b703c702bd", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 842, 850 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "114ff090-09b5-4bb7-8e32-47934f0a747e", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 931, 939 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b8bbae4d-5b06-436e-9286-df65e422c2a1", "type": "Gene", "text": [ "Pol beta" ], "offsets": [ [ 1082, 1090 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "514126c9-1ff8-43bd-a3ac-506414320171", "type": "title", "text": [ "Polymorphic Alu insertions and the genetic structure of Iberian Basques." ], "offsets": [ [ 0, 72 ] ] }, { "id": "5eb9cad2-2856-4716-bc7d-31abc390de99", "type": "abstract", "text": [ "Eight Alu sequences (ACE, TPA25, PV92, APO, FXIIIB, D1, A25 and B65) were analyzed in two samples from Navarre and Guipuzcoa provinces (Basque Country, Spain). Alu data for other European, Caucasus and North African populations were compiled from the literature for comparison purposes to assess the genetic relationships of the Basques in a broader geographic context. Results of both MDS plot and AMOVA revealed spatial heterogeneity among these three population clusters clearly defined by geography. On the contrary, no substantial genetic heterogeneity was found between the Basque samples, or between Basques and other Europeans (excluding Caucasus populations). Moreover, the genetic information obtained from Alu data conflicts with hypotheses linking the origin of Basques with populations from North Africa (Berbers) or from the Caucasus region (Georgia). In order to explain the reduced genetic heterogeneity detected by Alu insertions among Basque subpopulations, values of the Wright's F(ST )statistic were estimated for both Alu markers and a set of short tandem repeats (STRs) in terms of two geographical scales: (1) the Basque Country, (2) Europe (including Basques). In the Basque area, estimates of Wahlund's effect for both genetic markers showed no statistical difference between Basque subpopulations. However, when this analysis was performed on a European scale, F(ST) values were significantly higher for Alu insertions than for STR alleles. From these results, we suggest that the spatial heterogeneity of the Basque gene pool identified in previous polymorphism studies is relatively recent and probably caused by a differential process of genetic admixture with non-Basque neighboring populations modulated by the effect of a linguistic barrier to random mating." ], "offsets": [ [ 73, 1873 ] ] } ]

[ { "id": "a4fc7e68-d923-4a25-b23d-83f91421e26e", "type": "Gene", "text": [ "ACE" ], "offsets": [ [ 94, 97 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "62618e55-5352-4a08-812e-802f3f88051c", "type": "FamilyName", "text": [ "TPA25" ], "offsets": [ [ 99, 104 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "383e6f2b-ab3e-49b2-bc15-9f878da78c3a", "type": "FamilyName", "text": [ "PV92" ], "offsets": [ [ 106, 110 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "770c5163-9777-463c-9ac0-4861d752e079", "type": "Gene", "text": [ "APO" ], "offsets": [ [ 112, 115 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "82beb886-c7d1-4f58-bbff-8f9fe2b44e92", "type": "Gene", "text": [ "FXIIIB" ], "offsets": [ [ 117, 123 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2abdb19f-243a-414e-bcb1-c18ef29bd50c", "type": "FamilyName", "text": [ "D1" ], "offsets": [ [ 125, 127 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8f5d6194-2c66-4c03-871a-53151ce165fb", "type": "Gene", "text": [ "A25" ], "offsets": [ [ 129, 132 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cb4d06e9-147c-4824-aac0-e475eb3a9d7c", "type": "FamilyName", "text": [ "B65" ], "offsets": [ [ 137, 140 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "e74c9630-c145-4de5-a61f-a5a26513020a", "type": "title", "text": [ "Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States." ], "offsets": [ [ 0, 126 ] ] }, { "id": "ec4891e2-07b9-4047-9a8b-7d40765b17f0", "type": "abstract", "text": [ "Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder marked by hamartoma growth in multiple organ systems. We performed mutational analyses on 325 individuals with definite tuberous sclerosis complex diagnostic status. We identified mutations in 72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified. Genotype/phenotype analyses of all observed tuberous sclerosis complex findings in probands were performed, including several clinical features not analyzed in two previous large studies. We showed that patients with TSC2 mutations have significantly more hypomelanotic macules and learning disability in contrast to those with TSC1 mutations, findings not noted in previous studies. We also observed results consistent with two similar studies suggesting that individuals with mutations in TSC2 have more severe symptoms. On performing meta-analyses of our data and the other two largest studies in the literature, we found significant correlations for several features that individual studies did not have sufficient power to conclude. Male patients showed more frequent neurologic and eye symptoms, renal cysts, and ungual fibromas. Correlating genotypes with phenotypes should facilitate the disease management of tuberous sclerosis complex." ], "offsets": [ [ 127, 1539 ] ] } ]

[ { "id": "93b2ef58-14a3-4879-8e72-d5caf7e17167", "type": "FamilyName", "text": [ "tuberous sclerosis complex" ], "offsets": [ [ 78, 104 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "85d2354d-67a0-45e5-bb0b-b567f697606d", "type": "FamilyName", "text": [ "tuberous sclerosis complex" ], "offsets": [ [ 323, 349 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "68517815-334b-4f9c-99f9-459117dcefb2", "type": "Gene", "text": [ "TSC1" ], "offsets": [ [ 485, 489 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6cbd161c-ae1b-40e4-abda-5a3fdca56a82", "type": "Gene", "text": [ "TSC2" ], "offsets": [ [ 510, 514 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "961cd45b-6504-4dc9-9ebe-65fd60a2a7ba", "type": "FamilyName", "text": [ "tuberous sclerosis complex" ], "offsets": [ [ 638, 664 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "237f71ba-c7a7-499d-ac24-b7319b19cb7e", "type": "Gene", "text": [ "TSC2" ], "offsets": [ [ 811, 815 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b2030ddd-bcc9-4be2-840e-e6754494950e", "type": "Gene", "text": [ "TSC1" ], "offsets": [ [ 922, 926 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a0b08bdc-45d6-45b4-b906-41d0903ebdc2", "type": "Gene", "text": [ "TSC2" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d1936176-31ff-449d-8210-7b7a4064ca52", "type": "FamilyName", "text": [ "tuberous sclerosis complex" ], "offsets": [ [ 1512, 1538 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "09fd436f-f18c-4beb-b8ea-1223fd23d7c6", "type": "title", "text": [ "Disruption of a synaptotagmin (SYT14) associated with neurodevelopmental abnormalities." ], "offsets": [ [ 0, 87 ] ] }, { "id": "ab7b3f8d-1607-4cd3-a117-8188b03228b7", "type": "abstract", "text": [ "We report cytogenetic and molecular studies of a de novo, apparently balanced t(1;3)(q32.1;q25.1) identified in a 12-year-old female (designated DGAP128) with cerebral atrophy, macrocephaly seizures, and developmental delay. A combination of fluorescence in situ hybridization (FISH) and Southern blot analysis demonstrated disruption of a synaptotagmin gene (SYT14) at the 1q32 breakpoint. Expression of SYT14 in human brain was confirmed using Northern analysis. Because members of the synaptotagmin family of proteins function as sensors that link changes in calcium levels with a variety of biological processes, including neurotransmission and hormone-responsiveness, SYT14 is an intriguing candidate gene for the abnormal development in this child. This is the first known constitutional rearrangement of SYT14, and further systematic genetic analysis and clinical studies of DGAP128 may offer unique insights into the role of SYT14 in neurodevelopment." ], "offsets": [ [ 88, 1047 ] ] } ]

[ { "id": "4adc7dce-5f03-4bfe-a84c-e976c48dddb7", "type": "FamilyName", "text": [ "synaptotagmin" ], "offsets": [ [ 16, 29 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "32505425-51b7-495a-b0ca-96fb9a72b3ee", "type": "Gene", "text": [ "SYT14" ], "offsets": [ [ 31, 36 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8a71e0a7-8a05-4fec-8531-7ae604ee74ab", "type": "FamilyName", "text": [ "synaptotagmin" ], "offsets": [ [ 428, 441 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ee73a9ea-955c-4a5d-8167-2d876908e26c", "type": "Gene", "text": [ "SYT14" ], "offsets": [ [ 448, 453 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2f51add1-69ff-4a2e-a7e0-08e9bdb94a8e", "type": "Gene", "text": [ "SYT14" ], "offsets": [ [ 493, 498 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f10a26bf-a233-4020-8750-11dda322eeef", "type": "FamilyName", "text": [ "synaptotagmin" ], "offsets": [ [ 576, 589 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "85a8abe1-27db-4c33-92e4-e3333ca971f1", "type": "Gene", "text": [ "SYT14" ], "offsets": [ [ 761, 766 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b810205b-ddfe-4081-93e5-57b6df779996", "type": "Gene", "text": [ "SYT14" ], "offsets": [ [ 899, 904 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d9b8cd54-d637-46f0-8980-878d16f3ec98", "type": "Gene", "text": [ "SYT14" ], "offsets": [ [ 1021, 1026 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "f1184cf3-9774-4094-8636-051333850fd0", "type": "title", "text": [ "Interferon regulatory factor 6 (IRF6) and fibroblast growth factor receptor 1 (FGFR1) contribute to human tooth agenesis." ], "offsets": [ [ 0, 121 ] ] }, { "id": "5f8c77f6-d1d4-43fe-9ba6-c1b86603c016", "type": "abstract", "text": [ "Phenotypic characteristics expressed in syndromes give clues to the factors involved in the cause of isolated forms of the same defects. We investigated two genes responsible for craniofacial syndromes, FGFR1 and IRF6, in a collection of families with isolated tooth agenesis. Cheek swab samples were obtained for DNA analysis from 116 case/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. In addition, we studied 89 cases and 50 controls from Ohio to replicate any positive findings. Genotyping was performed by kinetic polymerase chain-reaction or TaqMan assays. Linkage disequilibrium analysis and transmission distortion of the marker alleles were performed. The same variants in the IRF6 gene that are associated with isolated orofacial clefts are also associated with human tooth agenesis (rs861019, P = 0.058; rs17015215-V274I, P = 0.0006; rs7802, P = 0.004). Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. The craniofacial phenotypic characteristics of these syndromes include oral clefts and preferential tooth agenesis of incisors and premolars, besides pits on the lower lips. Also it appears that preferential premolar agenesis is associated with FGFR1 (P = 0.014) and IRF6 (P = 0.002) markers. There were statistically significant data suggesting that IRF6 interacts not only with MSX1 (P = 0.001), but also with TGFA (P = 0.03)." ], "offsets": [ [ 122, 1536 ] ] } ]

[ { "id": "c3f6475c-e236-4ea0-adfc-a7866d10748d", "type": "Gene", "text": [ "Interferon regulatory factor 6" ], "offsets": [ [ 0, 30 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "25acd4c6-31e7-4660-b0e7-5c8fdf5bdef4", "type": "Gene", "text": [ "IRF6" ], "offsets": [ [ 32, 36 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3455b5ac-e30b-413f-b314-4817832a0e06", "type": "Gene", "text": [ "fibroblast growth factor receptor 1" ], "offsets": [ [ 42, 77 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "71cf50d4-2f10-4e8d-badf-a76ddc23f67b", "type": "Gene", "text": [ "FGFR1" ], "offsets": [ [ 79, 84 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4a4fa3ee-2578-4644-b2ad-02ca0879b3fb", "type": "Gene", "text": [ "FGFR1" ], "offsets": [ [ 325, 330 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0fd3c88d-6645-4647-9b6f-aa55e8770c37", "type": "Gene", "text": [ "IRF6" ], "offsets": [ [ 335, 339 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "add43121-acc6-44c3-812d-3b1fc3ac8db9", "type": "Gene", "text": [ "polymerase" ], "offsets": [ [ 689, 699 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "19c6eec4-cb42-4447-b757-e678dfb17528", "type": "Gene", "text": [ "IRF6" ], "offsets": [ [ 856, 860 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "371759e9-2fc7-4127-8189-5ffd3dcc431e", "type": "Gene", "text": [ "IRF6" ], "offsets": [ [ 1048, 1052 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1d8cc120-ff58-49b0-a23c-f47160a9d3a9", "type": "Gene", "text": [ "FGFR1" ], "offsets": [ [ 1353, 1358 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8feeba4-645f-4acf-9937-567e0e61928e", "type": "Gene", "text": [ "IRF6" ], "offsets": [ [ 1375, 1379 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6b24e8d6-d7ac-4ca1-a79b-9e3c7cf895d6", "type": "Gene", "text": [ "IRF6" ], "offsets": [ [ 1459, 1463 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4d7bdfe8-ee48-4115-a9c5-c08e60b5fb6d", "type": "Gene", "text": [ "MSX1" ], "offsets": [ [ 1488, 1492 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c569578b-7503-4b7d-987c-7878a96ae508", "type": "Gene", "text": [ "TGFA" ], "offsets": [ [ 1520, 1524 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c21afd6d-28db-4d3f-88b9-cfaf0043065f", "type": "title", "text": [ "Over-expression of BMP4 and BMP5 in a child with axial skeletal malformations and heterotopic ossification: a new syndrome." ], "offsets": [ [ 0, 123 ] ] }, { "id": "cfe59e01-f7fe-45e3-8263-5d6f6f5b17d5", "type": "abstract", "text": [ "Bone morphogenetic proteins (BMPs) are a highly conserved class of signaling molecules that induce ectopic cartilage and bone formation in vivo. Dysregulated expression of bone morphogenetic protein 4 (BMP4) is found in the cells of patients who have fibrodysplasia ossificans progressiva (FOP), a genetic disorder of axial and appendicular skeletal malformation and progressive heterotopic ossification. Loss of function mutations in the bone morphogenetic protein 5 (bmp5) gene leading to under-expression of BMP5 cause the murine short ear syndrome, characterized by small malformed ears and a broad range of axial skeletal malformations. We found features reminiscent of both the short ear mouse and FOP in a child with malformed external ears, multiple malformations of the axial skeleton, and progressive heterotopic ossification in the neck and back. We examined BMP mRNA expression in transformed lymphocytes by semi-quantitative RT-PCR and protein expression by ELISA assays and immunohistochemistry. Elevated levels of BMP4 and BMP5 mRNA and protein were detected in the patient's cells while levels of BMP2 mRNA were unchanged. Our data suggest that dysregulated expression of BMP4 and BMP5 genes is associated with an array of human axial skeletal abnormalities similar to the short ear mouse and FOP." ], "offsets": [ [ 124, 1442 ] ] } ]

[ { "id": "045d53f8-e2bb-4187-ad39-b191280b82f4", "type": "Gene", "text": [ "BMP4" ], "offsets": [ [ 19, 23 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8a053037-0074-4b3b-a60f-324958014bcd", "type": "Gene", "text": [ "BMP5" ], "offsets": [ [ 28, 32 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3a145c40-a53d-4d1c-8063-4eb03ec0c5b4", "type": "FamilyName", "text": [ "Bone morphogenetic proteins" ], "offsets": [ [ 124, 151 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d17408a8-4668-42d6-be01-3e64ecc31a7c", "type": "FamilyName", "text": [ "BMPs" ], "offsets": [ [ 153, 157 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "c7e8e05f-955a-448d-8317-9f417786e7c6", "type": "Gene", "text": [ "bone morphogenetic protein 4" ], "offsets": [ [ 296, 324 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e98eb74e-1fdf-4bc9-a0f2-cdcfac579325", "type": "Gene", "text": [ "BMP4" ], "offsets": [ [ 326, 330 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "e12c59fb-7848-4763-806e-9dc8c92cb81c", "type": "Gene", "text": [ "bone morphogenetic protein 5" ], "offsets": [ [ 563, 591 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "05295960-ae8a-4901-b89a-c23abe7f862e", "type": "Gene", "text": [ "bmp5" ], "offsets": [ [ 593, 597 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "ce637db8-da52-42af-b9e4-c58696defab8", "type": "Gene", "text": [ "BMP5" ], "offsets": [ [ 635, 639 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2aa4e3d8-ff4f-41bf-851e-ca57d2486c3f", "type": "Gene", "text": [ "BMP4" ], "offsets": [ [ 1153, 1157 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "438cd281-ffa8-4f96-a666-9f505ee4ad38", "type": "Gene", "text": [ "BMP5" ], "offsets": [ [ 1162, 1166 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a15a0ac9-1702-42a0-b373-0bbec490b616", "type": "Gene", "text": [ "BMP2" ], "offsets": [ [ 1242, 1246 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7c074e52-d861-4df1-9e68-b5ed0afb637f", "type": "Gene", "text": [ "BMP4" ], "offsets": [ [ 1317, 1321 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2c471b6a-ac1a-40d1-9206-8771f8284c00", "type": "Gene", "text": [ "BMP5" ], "offsets": [ [ 1326, 1330 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "c0510a99-a74a-4cf9-9948-e84fcfa00d7b", "type": "title", "text": [ "Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for autism." ], "offsets": [ [ 0, 88 ] ] }, { "id": "cf0bda64-bda3-45be-987e-05d522f44a37", "type": "abstract", "text": [ "Cytogenetic imbalances are increasingly being realized as causes of autism. Here, we report a de novo translocation between the short arms of chromosomes 15 and 16 in a female with autism, epilepsy, and global developmental delay. FISH analysis identified a cryptic deletion of approximately 160 kb at the boundary of the first exon and first intron of the 1.7 Mb ataxin-2 binding protein-1 (A2BP1) gene, also called FOX1. Quantitative real time PCR (Q-PCR) analysis verified a deletion of exon 1 in the 5' promoter region of the A2BP1 gene. Reverse transcription PCR (qRT-PCR) showed reduced mRNA expression in the individual's lymphocytes, demonstrating the functional consequence of the deletion. A2BP1 codes for a brain-expressed RNA binding or splicing factor. Because of emerging evidence in the role of RNA processing and gene regulation in pervasive developmental disorders, we performed further screening of A2BP1 in additional individuals with autism from the Autism Genetics Resource Exchange (AGRE) collection. Twenty-seven SNPs were genotyped across A2BP1 in 206 parent-child trios and two regions showed association at P < or = 0.008 level. No additional deletions or clear mutations were identified in 88 probands by re-sequencing of all exons and surrounding intronic regions or quantitative PCR (Q-PCR) of exon 1. Although only nominal association was observed, and no obvious causal mutations were identified, these results suggest that A2BP1 may affect susceptibility or cause autism in a subset of patients. Further investigations in a larger sample may provide additional information regarding the involvement of this gene in the autistic phenotype." ], "offsets": [ [ 89, 1772 ] ] } ]

[ { "id": "1185025f-7a75-40d2-a782-08f43567178a", "type": "Gene", "text": [ "A2BP1" ], "offsets": [ [ 46, 51 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0c0bab47-fc4d-4109-a78a-aa0192b12c21", "type": "Gene", "text": [ "FOX1" ], "offsets": [ [ 52, 56 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "541f9bca-7597-42bc-a2d5-aeabf2f67664", "type": "Gene", "text": [ "ataxin-2 binding protein-1" ], "offsets": [ [ 453, 479 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0424b204-cce6-4a44-ac55-d102cfcedda1", "type": "Gene", "text": [ "A2BP1" ], "offsets": [ [ 481, 486 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "21dccb81-80e8-4285-b113-c5f94892b6bc", "type": "Gene", "text": [ "FOX1" ], "offsets": [ [ 506, 510 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "bd336f5a-f33c-40b3-bab5-1f6745065065", "type": "Gene", "text": [ "A2BP1" ], "offsets": [ [ 624, 629 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "386bc1da-d61e-4667-a3e4-4839ebdcf259", "type": "Gene", "text": [ "A2BP1" ], "offsets": [ [ 799, 804 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4640cca0-bf5a-4270-9c7e-40c9af564b21", "type": "Gene", "text": [ "A2BP1" ], "offsets": [ [ 1016, 1021 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2d772365-c885-4830-9c05-1c7436071188", "type": "Gene", "text": [ "A2BP1" ], "offsets": [ [ 1162, 1167 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "88ea64da-2c04-4532-8c77-b44f8b534869", "type": "Gene", "text": [ "A2BP1" ], "offsets": [ [ 1557, 1562 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "84772b6d-7acb-4e1d-b54d-634bc4ef3f6e", "type": "title", "text": [ "The IRF5 polymorphism in type 1 diabetes." ], "offsets": [ [ 0, 41 ] ] }, { "id": "7026a04c-cdfa-43d6-a294-c2d5038e662e", "type": "abstract", "text": [ "The interferon regulatory factor 5 gene (IRF5) has been shown to play a crucial role in harmful immune responses by induction of proinflammatory cytokines. Functional genetic variants associated with increased IRF5 expression of specific isoforms are associated with systemic lupus erythematosus (SLE) and it is possible that they may also predispose to other autoimmune disorders. We tested the association of two IRF5 SNPs, correlated with IRF5 expression and SLE risk, in 947 nuclear family trios type 1 diabetes (T1D) using the transmission disequilibrium test. Our results suggest that the functional IRF5 variations do not confer an obvious risk for T1D." ], "offsets": [ [ 42, 702 ] ] } ]

[ { "id": "77675c4c-ed5e-40c0-8bd4-7a402abe8ad3", "type": "Gene", "text": [ "IRF5" ], "offsets": [ [ 4, 8 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4137d52d-9bf7-444b-ac0d-2c234d0f3d39", "type": "Gene", "text": [ "interferon regulatory factor 5" ], "offsets": [ [ 46, 76 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "28c1832a-d40f-4b0c-a170-196889a3a53c", "type": "Gene", "text": [ "IRF5" ], "offsets": [ [ 83, 87 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "96cacb6a-719d-47fc-af98-12bf085b6c40", "type": "Gene", "text": [ "IRF5" ], "offsets": [ [ 252, 256 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "552c4c45-6e3f-4a11-926c-87fb1c86914d", "type": "Gene", "text": [ "IRF5" ], "offsets": [ [ 457, 461 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d74db62d-eb8a-4fb4-83fd-250e3f48bd51", "type": "Gene", "text": [ "IRF5" ], "offsets": [ [ 484, 488 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d550c228-3960-49e5-a12c-6790912c5beb", "type": "Gene", "text": [ "IRF5" ], "offsets": [ [ 648, 652 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "06374b34-199b-4daa-bd76-3420489ade79", "type": "title", "text": [ "Single nucleotide polymorphisms of cytokine genes in the healthy Slovak population." ], "offsets": [ [ 0, 83 ] ] }, { "id": "3fe3ae06-2b13-4ae7-aa3d-332a7b33d598", "type": "abstract", "text": [ "Cytokines are molecules that control and modulate the activities of numerous target cells via binding to specific receptors. The observed differences in the cytokine production among individuals can be, at least partially, explained by gene polymorphisms. Several cytokine gene polymorphisms have been identified to play a role in susceptibility to various diseases, including autoimmune, infectious, allergic or cardiovascular diseases. The aim of the current study was to determine allele and genotype frequencies of 22 polymorphisms in 13 cytokine genes in the healthy Slovak population and to compare them with data available from six populations from Central and Southern Europe. A polymerase chain reaction with sequence-specific primers was used to genotype polymorphisms within genes encoding IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-4Ralpha, IL-12, IFN-gamma, TGF-beta, TNF-alpha, IL-2, IL-4, IL-6 and IL-10 in a sample of 140 unrelated Slovak subjects. The allelic distribution of all polymorphisms in the Slovak population was very close to that in the geographically and historically closest populations in Central Europe--the Czech and the Polish. However, several differences were found between the Slovak and four populations from Southern Europe. The obtained data represent a basis for further studies on association of cytokine gene polymorphisms with some diseases." ], "offsets": [ [ 84, 1466 ] ] } ]

[ { "id": "7e964afe-1e05-4c97-bc41-591e8c22a36c", "type": "FamilyName", "text": [ "cytokine" ], "offsets": [ [ 35, 43 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2279a6af-3c6e-4532-a7f6-4e511719d304", "type": "FamilyName", "text": [ "cytokine" ], "offsets": [ [ 241, 249 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "adf3e331-6a60-4e72-86fe-e14a46bb812c", "type": "FamilyName", "text": [ "cytokine" ], "offsets": [ [ 348, 356 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "607b5c87-39a5-4b58-a703-060724233a27", "type": "FamilyName", "text": [ "cytokine" ], "offsets": [ [ 626, 634 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "318e50f3-4ea8-4976-8ed0-a10f38d95f1d", "type": "Gene", "text": [ "IL-1alpha" ], "offsets": [ [ 885, 894 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "deb6cddc-fd14-4dc2-bc32-e126b241116a", "type": "Gene", "text": [ "IL-1beta" ], "offsets": [ [ 896, 904 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "be601aa6-441b-4136-a3fc-ebbc6951cb97", "type": "FamilyName", "text": [ "IL-1R" ], "offsets": [ [ 906, 911 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "50585c73-8697-4dab-893c-985ad1260b98", "type": "Gene", "text": [ "IL-1RA" ], "offsets": [ [ 913, 919 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d3965a7b-3349-4e99-ab5b-3f9a067ab5fd", "type": "Gene", "text": [ "IL-4Ralpha" ], "offsets": [ [ 921, 931 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0064334b-7144-4ca8-b547-e31bb8801642", "type": "FamilyName", "text": [ "IL-12" ], "offsets": [ [ 933, 938 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "8cab9674-d0ef-46b1-9f14-8082484b192d", "type": "Gene", "text": [ "IFN-gamma" ], "offsets": [ [ 940, 949 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3bf39a28-a2ed-454b-b7a0-8982d22e431d", "type": "FamilyName", "text": [ "TGF-beta" ], "offsets": [ [ 951, 959 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1ea5c7e4-2c5a-4ca7-8ade-160dd1fe7580", "type": "Gene", "text": [ "TNF-alpha" ], "offsets": [ [ 961, 970 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f591c67b-556b-4625-86f1-7a2f94e881c0", "type": "Gene", "text": [ "IL-2" ], "offsets": [ [ 972, 976 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "792a0018-0f16-49aa-ae85-8771d6eda184", "type": "Gene", "text": [ "IL-4" ], "offsets": [ [ 978, 982 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "44489b39-5795-4afc-8db8-22b0b7302c7e", "type": "Gene", "text": [ "IL-6" ], "offsets": [ [ 984, 988 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d303ecba-93ee-478b-97a8-74d22d6c79cc", "type": "Gene", "text": [ "IL-10" ], "offsets": [ [ 993, 998 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6bd8872d-356d-4ea8-ba44-ff42bbea1b69", "type": "FamilyName", "text": [ "cytokine" ], "offsets": [ [ 1419, 1427 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "d9d71b05-f646-4d63-856d-eb0b0a81fdef", "type": "title", "text": [ "Identifying haplotype block structure using an ancestor-derived model." ], "offsets": [ [ 0, 70 ] ] }, { "id": "3e1117bb-b472-4f9d-94bb-92742b17364d", "type": "abstract", "text": [ "Recently, haplotype-based association studies have become popular for detecting disease-related or drug-response-associated genes. In these studies, it has been gradually recognized that a haplotype block structure is important. A rational and automatic method for identifying the haplotype block structure from SNP data has been desired. We have developed a new method using an ancestor-derived model and the minimum description length principle. The proposed method was applied to real data on the TAP2 gene in which a recombination hotspot was previously reported in human sperm data. The proposed method could identify an appropriate haplotype block structure, while existing methods failed. The performance of the proposed method was also investigated in a simulation study. The proposed method presented a better performance in real data analysis and the simulation study than existing methods. The proposed method was powerful from the viewpoint of hotspot sensitivity and was robust to mutation except at the edge of a sequence." ], "offsets": [ [ 71, 1107 ] ] } ]

[ { "id": "d5b5dd98-3738-451e-860f-c111c4b48576", "type": "Gene", "text": [ "TAP2" ], "offsets": [ [ 571, 575 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "d142b714-05d9-4863-b804-6335342d83b8", "type": "title", "text": [ "A microduplication of CBP in a patient with mental retardation and a congenital heart defect." ], "offsets": [ [ 0, 93 ] ] }, { "id": "2e5df8f5-4cfa-4319-ad98-b9f066dd489c", "type": "abstract", "text": [ "Rubinstein-Taybi syndrome is a well-characterized genetic syndrome caused by haploinsufficiency of CBP in a majority of individuals. In 10% of cases a microdeletion in 16p13.3 affecting CBP is detected. We report on a patient with a de novo 345-480 kb micro-duplication the region, encompassing only CBP and TRAP1. This boy presented with various minor physical anomalies, moderate mental retardation, and an atrial septal defect, but none of the other typical characteristics of the Rubinstein-Taybi syndrome, such as the broad thumbs and first toes or facial characteristics. This finding implicates CBP as one of the causative genes for the trisomy 16p13 syndrome, and indicates this is a contiguous gene syndrome." ], "offsets": [ [ 94, 811 ] ] } ]

[ { "id": "9e0a6978-6412-4080-b500-4210ecf2aa98", "type": "Gene", "text": [ "CBP" ], "offsets": [ [ 22, 25 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "30e812b5-993c-4202-989b-3f37bd026dc7", "type": "Gene", "text": [ "CBP" ], "offsets": [ [ 193, 196 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2032d838-fe54-463a-b2bf-06bf9feeb5b6", "type": "Gene", "text": [ "CBP" ], "offsets": [ [ 280, 283 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4530ba21-68eb-4878-81c9-f6872a8a14c4", "type": "Gene", "text": [ "CBP" ], "offsets": [ [ 394, 397 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b83f47da-8216-4350-91e1-2f6f2de8abf9", "type": "Gene", "text": [ "TRAP1" ], "offsets": [ [ 402, 407 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "00c60ce7-6bb3-435b-876c-2249a1f0f43f", "type": "Gene", "text": [ "CBP" ], "offsets": [ [ 696, 699 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "6f4bcbda-c9b8-4c54-89f5-8b6e96254a10", "type": "title", "text": [ "Myxoinflammatory fibroblastic sarcoma showing t(2;6)(q31;p21.3) as a sole cytogenetic abnormality." ], "offsets": [ [ 0, 98 ] ] }, { "id": "2481d274-af60-439c-98fc-6c298179e68e", "type": "abstract", "text": [ "Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade sarcoma characterized by distinctive, large, and bizarre Reed--Sternberg--like cells associated with an intense inflammatory infiltrate. The biology of MIFS is still poorly understood, and only two previous cases had been studied cytogenetically. In the present case, analysis of MIFS in the foot of a 53-year-old man revealed the chromosome translocation t(2;6)(q31;p21.3) as the only cytogenetic abnormality. This finding is distinct from the two cases previously reported. Additional studies are needed to verify whether any of these chromosome rearrangements are involved recurrently in MIFS." ], "offsets": [ [ 99, 761 ] ] } ]

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[ { "id": "799c5f6d-3771-4841-9d1c-42fcd969a047", "type": "title", "text": [ "Identities, frequencies and origins of TMC1 mutations causing DFNB7/B11 deafness in Pakistan." ], "offsets": [ [ 0, 93 ] ] }, { "id": "e81d129a-5d7b-4296-92dd-260b784bec0f", "type": "abstract", "text": [ "Non-syndromic deafness is genetically heterogeneous. We previously reported that mutations of transmembrane channel-like gene 1 (TMC1) cause non-syndromic recessive deafness at the DFNB7/B11 locus on chromosome 9q13-q21 in nine Pakistani families. The goal of this study was to define the identities, origins and frequencies of TMC1 mutations in an expanded cohort of 557 large Pakistani families segregating recessive deafness. We screened affected family members for homozygosity at short-tandem repeats flanking known autosomal recessive (DFNB) deafness loci, followed by TMC1 sequence analysis in families segregating deafness linked to DFNB7/B11. We identified 10 new families segregating DFNB7/B11 deafness and TMC1 mutations, including three novel alleles. Overall, 9 different TMC1 mutations account for deafness in 19 (3.4%) of the 557 Pakistani families. A single mutation, p.R34X, causes deafness in 10 (1.8%) of the families. Genotype analysis of p.R34X-linked markers indicates that it arose from a common founder. We also detected p.R34X among normal control samples of African-American and northern European origins, raising the possibility that p.R34X and other mutations of TMC1 are prevalent contributors to the genetic load of deafness across a variety of populations and continents." ], "offsets": [ [ 94, 1396 ] ] } ]

[ { "id": "fcd34025-9a55-487f-816c-4a77ca5d396d", "type": "Gene", "text": [ "TMC1" ], "offsets": [ [ 39, 43 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7115470e-a94a-4fb5-9d80-6752c7d875c3", "type": "Gene", "text": [ "DFNB7/B11" ], "offsets": [ [ 62, 71 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "154dfadd-d634-4387-b5ad-d77521a52bea", "type": "Gene", "text": [ "transmembrane channel-like gene 1" ], "offsets": [ [ 188, 221 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b5cce12a-4d26-4c11-907f-8fd7f0106780", "type": "Gene", "text": [ "TMC1" ], "offsets": [ [ 223, 227 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "36a4d10a-9faa-4ed8-8b09-3c52a53c0a91", "type": "Gene", "text": [ "DFNB7/B11" ], "offsets": [ [ 275, 284 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "a9f4355f-7c01-4948-8a79-7eecefe75a94", "type": "Gene", "text": [ "TMC1" ], "offsets": [ [ 422, 426 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "269710e4-6bf0-4ec2-bf50-7c72a9d2eef5", "type": "Gene", "text": [ "TMC1" ], "offsets": [ [ 669, 673 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1cc03bbb-af1b-46f6-8da2-a1f3e0e6e63b", "type": "Gene", "text": [ "DFNB7/B11" ], "offsets": [ [ 735, 744 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1030c848-e49c-4896-b9ff-b6a5b6024556", "type": "Gene", "text": [ "DFNB7/B11" ], "offsets": [ [ 788, 797 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1bcbe436-5cc9-40f2-821f-ff057ff0b4aa", "type": "Gene", "text": [ "TMC1" ], "offsets": [ [ 811, 815 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "eca14d65-ca4b-4e28-bb36-b4d688d8cd61", "type": "Gene", "text": [ "TMC1" ], "offsets": [ [ 879, 883 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "6f71629d-640a-4e1b-a48f-552ede15bf04", "type": "Gene", "text": [ "TMC1" ], "offsets": [ [ 1285, 1289 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "53de8c4b-87ea-40f9-a91a-4fdd07efcc89", "type": "title", "text": [ "Pharmacokinetic and pharmacodynamic basis for partial protection against alcoholism in Asians, heterozygous for the variant ALDH2*2 gene allele." ], "offsets": [ [ 0, 144 ] ] }, { "id": "f40f70a7-0525-4558-b047-93d1b887ac69", "type": "abstract", "text": [ "OBJECTIVES: It has been well documented that although homozygosity of the variant aldehyde dehydrogenase-2 (ALDH2) gene allele, ALDH2*2, in Asians almost fully protects against alcoholism, the heterozygosity only affords a partial protection to varying degrees. The full protection against alcoholism has been ascribed to the low-amount of alcohol hypersensitivity accompanied by a prolonged and large accumulation of acetaldehyde in blood (Peng et al. Pharmacogenetics 1999; 9:463-476). The physiological basis for the partial protection, however, remains unclear. METHODS: To address this question, we recruited a total of 32 adult Han Chinese men, matched by age, body-mass index, and nutritional state from a population base of 404 men. The subjects were divided into 3 combinatorial genotypic groups of alcohol dehydrogenase (ADH) and ALDH, that is, ALDH2*1/*1-ADH1B*1/*1-ADH1C*1/*1 (n=8), ALDH2*1/*1-ADH1B*2/*2-ADH1C*1/*1 (n=8), and ALDH2*1/*2-ADH1B*2/*2-ADH1C*1/*1 (n=16). Following a moderate dose of ethanol (0.5 g/kg body weight), blood ethanol/acetaldehyde/acetate concentrations, cardiac and extracranial/intracranial arterial hemodynamic parameters, as well as self-rated subjective sensations, were measured for 130 min. RESULTS: Heterozygotic ALDH2*1/*2 subjects were found to be strikingly responsive to the moderate amount of alcohol, as evidenced by the prominent cardiovascular effects as well as subjective perceptions of general discomfort for as long as 2 h following ingestion. The ADH1B polymorphisms did not appear to correlate with the pharmacokinetic and pharmacodynamic effects. CONCLUSIONS: These results indicate that acetaldehyde, rather than ethanol or acetate, is primarily responsible for the observed alcohol sensitivity reactions and suggest that substantially lower accumulation of blood acetaldehyde in the heterozygotes significantly reduces the aversion reaction to low amounts of alcohol that permits other biological as well as environmental factors to facilitate drinking and the according risk for the disease." ], "offsets": [ [ 145, 2199 ] ] } ]

[ { "id": "2a3b0af8-554d-43c3-b748-c3aef3586217", "type": "Gene", "text": [ "ALDH2" ], "offsets": [ [ 124, 129 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d8555efd-d5df-42aa-b3fc-137f1eb2aeee", "type": "Gene", "text": [ "aldehyde dehydrogenase-2" ], "offsets": [ [ 227, 251 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "02cfb775-f2ea-4c7c-85a9-bb6822ea615c", "type": "Gene", "text": [ "ALDH2" ], "offsets": [ [ 253, 258 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "b0a1b1c4-8c61-4f36-b6ef-d54acd4fbcb3", "type": "Gene", "text": [ "ALDH2" ], "offsets": [ [ 273, 278 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "426a34f5-dc99-4d25-aac1-09ef6d1b2fc7", "type": "FamilyName", "text": [ "alcohol dehydrogenase" ], "offsets": [ [ 953, 974 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2c982ee9-dbfd-4245-900a-11c7862ab13a", "type": "FamilyName", "text": [ "ADH" ], "offsets": [ [ 976, 979 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "f817df7c-e464-4a7e-a98d-1cf6eb61a53b", "type": "FamilyName", "text": [ "ALDH" ], "offsets": [ [ 985, 989 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "61243fc1-d556-4ff7-8671-89c356500626", "type": "Gene", "text": [ "ALDH2" ], "offsets": [ [ 1000, 1005 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "1579780d-0eae-4fa9-8621-700992d49174", "type": "Gene", "text": [ "ADH1B" ], "offsets": [ [ 1011, 1016 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "16af31ba-1c69-48df-9a68-6bf92582ad3c", "type": "Gene", "text": [ "ADH1C" ], "offsets": [ [ 1022, 1027 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cdabbfc2-d4ff-4a8f-afe6-176d5533d04b", "type": "Gene", "text": [ "ALDH2" ], "offsets": [ [ 1040, 1045 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "24222dce-fd36-4a98-bca7-f76d6ce660b7", "type": "Gene", "text": [ "ADH1B" ], "offsets": [ [ 1051, 1056 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d5eb8797-923f-48ff-8882-4d60b6dbc095", "type": "Gene", "text": [ "ADH1C" ], "offsets": [ [ 1062, 1067 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d3d10e21-7e17-4542-9f33-5b9e8b7285c7", "type": "Gene", "text": [ "ALDH2" ], "offsets": [ [ 1084, 1089 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "3c66cb58-eacb-4c54-9eed-d9ab4bce8556", "type": "Gene", "text": [ "ADH1B" ], "offsets": [ [ 1095, 1100 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "d20c7a2f-5094-45b8-bf3e-f0a4755c1e68", "type": "Gene", "text": [ "ADH1C" ], "offsets": [ [ 1106, 1111 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "5da5f710-c9bf-4b30-a105-9d8eebc95771", "type": "Gene", "text": [ "ALDH2" ], "offsets": [ [ 1403, 1408 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "2fe36a38-a7f7-431a-9cfc-2061605b1377", "type": "Gene", "text": [ "ADH1B" ], "offsets": [ [ 1650, 1655 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "5ee2c661-85c5-41a0-b44d-7c06a29935a9", "type": "title", "text": [ "Identification of rare variants in the hLIMD1 gene in breast cancer." ], "offsets": [ [ 0, 68 ] ] }, { "id": "14202821-a326-4d90-82f6-0855d4bdb5be", "type": "abstract", "text": [ "The hLIMD1 gene is located at chromosome 3p21 and was identified as a putative tumor suppressor gene using an elimination test assay. Chromosome 3p21 loci are frequently deleted in a number of cancers, including breast. The 3p21.3 locus harbors a number of tumor suppressor candidates, including LIMD1, a member of the ZYXIN family of genes. LIMD1 directly interacts with RB and is thought to play a role in suppressing tumor growth. To investigate whether mutations in the LIMD1 gene could potentially be involved in breast cancer, we used single-stranded conformation polymorphism analysis on DNA from 235 breast cancers and 95 controls. We identified four novel coding region alterations, including two amino acid substitutions at positions 255 and 302. The two remaining novel variants were found at amino acid positions 246 and 647 and encoded silent alterations. The rare Ser255Arg variant was identified in only sporadic breast tumors (2/165 tumors). Some ZYXIN proteins are phosphorylated by serine/threonine kinases, and the Ser255Arg change is located in a region phosphorylated on serine residues. Together, the data suggest that this variant may warrant further characterization." ], "offsets": [ [ 69, 1260 ] ] } ]

[ { "id": "1f2adb37-9397-416d-83a0-fa5a24f03a37", "type": "Gene", "text": [ "hLIMD1" ], "offsets": [ [ 39, 45 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "029211eb-1349-4aab-9b56-5101bfcb8b75", "type": "Gene", "text": [ "hLIMD1" ], "offsets": [ [ 73, 79 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "cae83480-5a02-4f76-ae31-493bfe6af1aa", "type": "FamilyName", "text": [ "tumor suppressor" ], "offsets": [ [ 148, 164 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "95642087-94d2-41f7-a63c-a4cdeac91ee3", "type": "Gene", "text": [ "LIMD1" ], "offsets": [ [ 365, 370 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "af210787-e762-4d72-a6de-45f44b5384d5", "type": "Gene", "text": [ "ZYXIN" ], "offsets": [ [ 388, 393 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "004e673a-b702-46dc-bcb2-5bcb1beb2171", "type": "Gene", "text": [ "LIMD1" ], "offsets": [ [ 411, 416 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "7b11acfd-a031-4745-a3da-8722cddb58a0", "type": "Gene", "text": [ "LIMD1" ], "offsets": [ [ 543, 548 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "0323bab7-1f93-4f19-9996-b618f507574a", "type": "Gene", "text": [ "ZYXIN" ], "offsets": [ [ 1032, 1037 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "7fb320f3-1509-4f86-ab1e-74d14bb9d05e", "type": "title", "text": [ "Kidney failure in Townes-Brocks syndrome: an under recognized phenomenon?" ], "offsets": [ [ 0, 73 ] ] }, { "id": "83fa6a48-a703-4f40-b453-49b84bbbc2e5", "type": "abstract", "text": [ "Though uncommon, kidney malformations are described in several cases of Townes-Brocks syndrome. By contrast, kidney failure has been reported as the presenting feature of Townes-Brocks syndrome on only one occasion. While the SALL1 gene, mutations of which result in the Townes-Brocks phenotype, is expressed in the developing kidney, the absence of other corroborative reports of kidney failure presenting in affected individuals suggests that the solitary observation of kidney failure is as likely due to chance as to causal association. In now reporting a further instance of this association, we review the literature, demonstrating that several other instances of kidney failure are in fact known, despite an incomplete dataset. These findings suggest that kidney failure may be a constituent element of the natural history of Townes-Brocks syndrome and raise the possible benefits of longitudinal survey for progressive kidney impairment in patients with this syndrome." ], "offsets": [ [ 74, 1050 ] ] } ]

[ { "id": "5efa9172-da40-459f-bfa0-934ed2404176", "type": "Gene", "text": [ "SALL1" ], "offsets": [ [ 300, 305 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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[ { "id": "1d731638-d6a6-4e5c-9702-5075423753a7", "type": "title", "text": [ "Clinical and molecular characterization of Italian patients affected by Cohen syndrome." ], "offsets": [ [ 0, 87 ] ] }, { "id": "80684c5a-05c2-48ba-b846-5955a1a972f5", "type": "abstract", "text": [ "Cohen syndrome is an autosomal recessive disorder with variability in the clinical manifestations, characterized by developmental delay, visual disability, facial dysmorphisms and intermittent neutropenia. We described a cohort of 10 patients affected by Cohen syndrome from nine Italian families ranging from 5 to 52 years at assessment. Characteristic age related facial changes were well documented. Visual anomalies, namely retinopathy and myopia, were present in 9/10 patients (retinopathy in 9/10 and myopia in 8/10). Truncal obesity has been described in all patients older than 6 years (8/8). DNA samples from all patients were analyzed for mutations in COH1 by DHPLC. We detected 15 COH1 alterations most of them were truncating mutations, only one being a missense change. Partial gene deletions have been found in two families. Most mutations were private. Two were already reported in the literature just once. A single base deletion leading to p.T3708fs3769, never reported before, was found in three apparently unrelated families deriving from a restricted area of the Veneto's lowland, between Padova town and Tagliamento river, in heterozygous state. Given the geographical conformation of this region, which is neither geographically or culturally isolated, a recent origin of the mutation could be hypothesized." ], "offsets": [ [ 88, 1422 ] ] } ]

[ { "id": "6e63c51f-53d8-4d55-a363-c6b0b7822846", "type": "Gene", "text": [ "COH1" ], "offsets": [ [ 750, 754 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] }, { "id": "4a6a6270-ae33-4713-92d7-907bdb910ce7", "type": "Gene", "text": [ "COH1" ], "offsets": [ [ 780, 784 ] ], "normalized": [ { "db_name": "", "db_id": "" } ] } ]

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