Brizape/SETH_split_0404_dev · Datasets at Hugging Face

id stringlengths 7 8	tokens sequence	ner_tags sequence	texts stringlengths 31 3.46k
7762554	[ "Frequent", "intragenic", "deletion", "of", "the", "P", "gene", " ", "in", "Tanzanian", "patients", "with", "type", "II", "oculocutaneous", "albinism", "(OCA2).", "Type", "II", "oculocutaneous", "albinism", "(OCA2)", "is", "an", "autosomal", "recessive", "disorder", "in", "which", "the", "biosynthesis", "of", "melanin", "pigment", "is", "reduced", "in", "the", "skin,", "hair,", "and", "eyes.", "OCA2,", "which", "results", "from", "mutations", "of", "the", "P", "gene", ",", "is", "the", "most", "frequent", "type", "of", "albinism", "in", "African", "and", "African-American", "patients.", "OCA2", "is", "especially", "frequent", "in", "Tanzania,", "where", "it", "occurs", "with", "an", "incidence", "of", "approximately", "1/1,400.", "We", "have", "identified", "abnormalities", "of", "the", "P", "gene", " ", "in", "each", "of", "13", "unrelated", "patients", "with", "OCA2", "from", "Tanzania.", "One", "of", "these,", "a", "deletion", "of", "exon", "7,", "is", "strongly", "predominant,", "accounting", "for", "approximately", "77%", "of", "mutant", "alleles", "in", "this", "group", "of", "patients." ]	[ 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2). Type II oculocutaneous albinism (OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in the skin, hair, and eyes. OCA2, which results from mutations of the P gene , is the most frequent type of albinism in African and African-American patients. OCA2 is especially frequent in Tanzania, where it occurs with an incidence of approximately 1/1,400. We have identified abnormalities of the P gene in each of 13 unrelated patients with OCA2 from Tanzania. One of these, a deletion of exon 7, is strongly predominant, accounting for approximately 77% of mutant alleles in this group of patients.
16395665	[ "Prioritizing", "regions", "of", "candidate", "genes", "for", "efficient", "mutation", "screening.", "The", "availability", "of", "the", "complete", "sequence", "of", "the", "human", "genome", "has", "dramatically", "facilitated", "the", "search", "for", "disease-causing", "sequence", "variations.", "In", "fact,", "the", "rate-limiting", "step", "has", "shifted", "from", "the", "discovery", "and", "characterization", "of", "candidate", "genes", "to", "the", "actual", "screening", "of", "human", "populations", "and", "the", "subsequent", "interpretation", "of", "observed", "variations.", "In", "this", "study", "we", "tested", "the", "hypothesis", "that", "some", "segments", "of", "candidate", "genes", "are", "more", "likely", "than", "others", "to", "contain", "disease-causing", "variations", "and", "that", "these", "segments", "can", "be", "predicted", "bioinformatically.", "A", "bioinformatic", "technique,", "prioritization", "of", "annotated", "regions", "(PAR),", "was", "developed", "to", "predict", "the", "likelihood", "that", "a", "specific", "coding", "region", "of", "a", "gene", "will", "harbor", "a", "disease-causing", "mutation", "based", "on", "conserved", "protein", "functional", "domains", "and", "protein", "secondary", "structures.", "This", "method", "was", "evaluated", "by", "using", "it", "to", "analyze", "710", "genes", "that", "collectively", "harbor", "4,498", "previously", "identified", "mutations.", "Nearly", "50%", "of", "the", "genes", "were", "recognized", "as", "disease-associated", "after", "screening", "only", "9%", "of", "the", "complete", "coding", "sequence.", "The", "PAR", "technique", "identified", "90%", "of", "the", "genes", "as", "containing", "at", "least", "one", "mutation,", "with", "less", "than", "40%", "of", "the", "screening", "resources", "that", "traditional", "approaches", "would", "require.", "These", "results", "suggest", "that", "prioritization", "strategies", "such", "as", "PAR", "can", "accelerate", "disease-gene", "identification", "through", "more", "efficient", "use", "of", "screening", "resources." ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]	Prioritizing regions of candidate genes for efficient mutation screening. The availability of the complete sequence of the human genome has dramatically facilitated the search for disease-causing sequence variations. In fact, the rate-limiting step has shifted from the discovery and characterization of candidate genes to the actual screening of human populations and the subsequent interpretation of observed variations. In this study we tested the hypothesis that some segments of candidate genes are more likely than others to contain disease-causing variations and that these segments can be predicted bioinformatically. A bioinformatic technique, prioritization of annotated regions (PAR), was developed to predict the likelihood that a specific coding region of a gene will harbor a disease-causing mutation based on conserved protein functional domains and protein secondary structures. This method was evaluated by using it to analyze 710 genes that collectively harbor 4,498 previously identified mutations. Nearly 50% of the genes were recognized as disease-associated after screening only 9% of the complete coding sequence. The PAR technique identified 90% of the genes as containing at least one mutation, with less than 40% of the screening resources that traditional approaches would require. These results suggest that prioritization strategies such as PAR can accelerate disease-gene identification through more efficient use of screening resources.
15365989	[ "Novel", "homozygous", "p.E64D", " ", "mutation", "in", "DJ1", " ", "in", "early", "onset", "Parkinson", "disease", "(PARK7).", "Mutations", "in", "the", "parkin", "gene", "have", "been", "identified", "as", "a", "common", "cause", "of", "autosomal", "recessive", "inherited", "Parkinson", "disease", "(PD)", "associated", "with", "early", "disease", "manifestation.", "However,", "based", "on", "linkage", "data,", "mutations", "in", "other", "genes", "contribute", "to", "the", "genetic", "heterogeneity", "of", "early-onset", "PD", "(EOPD).", "Recently,", "two", "mutations", "in", "the", "DJ1", " ", "gene", "were", "described", "as", "a", "second", "cause", "of", "autosomal", "recessive", "EOPD", "(PARK7).", "Analyzing", "the", "PARK7", "PARK7", ").", "Analyzing", "the", "PARK7/", "DJ1", " ", "gene", "in", "104", "EOPD", "patients,", "we", "identified", "a", "third", "mutation,", "c.192G>C", " ", "(", "p.E64D", "),", "associated", "with", "EOPD", "in", "a", "patient", "of", "Turkish", "ancestry", "and", "characterized", "the", "functional", "significance", "of", "this", "amino", "acid", "substitution.", "In", "the", "patient,", "a", "substantial", "reduction", "of", "dopamine", "uptake", "transporter", "(DAT)", "binding", "was", "found", "in", "the", "striatum", "using", "[(18)F]FP-CIT", "and", "PET,", "indicating", "a", "serious", "loss", "of", "presynaptic", "dopaminergic", "afferents.", "His", "sister,", "homozygous", "for", "E64D,", "was", "clinically", "unaffected", "but", "showed", "reduced", "dopamine", "uptake", "when", "compared", "with", "a", "clinically", "unaffected", "brother,", "who", "is", "heterozygous", "for", "E64D", "E64D", ",", "was", "clinically", "unaffected", "but", "showed", "reduced", "dopamine", "uptake", "when", "compared", "with", "a", "clinically", "unaffected", "brother,", "who", "is", "heterozygous", "for", "E64D.", "We", "demonstrate", "by", "crystallography", "that", "the", "E64D", " ", "mutation", "does", "not", "alter", "the", "structure", "of", "the", "DJ1", " ", "protein,", "however", "we", "observe", "a", "tendency", "towards", "decreased", "levels", "of", "the", "mutant", "protein", "when", "overexpressed", "in", "HEK293", "or", "COS7", "cells.", "Using", "immunocytochemistry", "in", "contrast", "to", "the", "homogenous", "nuclear", "and", "cytoplasmic", "staining", "in", "HEK293", "cells", "overexpressing", "wild-type", "DJ1", ",", "about", "5%", "of", "the", "cells", "expressing", "E64D", " ", "and", "up", "to", "80%", "of", "the", "cells", "expressing", "the", "recently", "described", "L166P", " ", "mutation", "displayed", "a", "predominant", "nuclear", "localization", "of", "the", "mutant", "DJ1", " ", "protein." ]	[ 0, 0, 3, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0 ]	Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Mutations in the parkin gene have been identified as a common cause of autosomal recessive inherited Parkinson disease (PD) associated with early disease manifestation. However, based on linkage data, mutations in other genes contribute to the genetic heterogeneity of early-onset PD (EOPD). Recently, two mutations in the DJ1 gene were described as a second cause of autosomal recessive EOPD (PARK7). Analyzing the PARK7 PARK7 ). Analyzing the PARK7/ DJ1 gene in 104 EOPD patients, we identified a third mutation, c.192G>C ( p.E64D ), associated with EOPD in a patient of Turkish ancestry and characterized the functional significance of this amino acid substitution. In the patient, a substantial reduction of dopamine uptake transporter (DAT) binding was found in the striatum using [(18)F]FP-CIT and PET, indicating a serious loss of presynaptic dopaminergic afferents. His sister, homozygous for E64D, was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who is heterozygous for E64D E64D , was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who is heterozygous for E64D. We demonstrate by crystallography that the E64D mutation does not alter the structure of the DJ1 protein, however we observe a tendency towards decreased levels of the mutant protein when overexpressed in HEK293 or COS7 cells. Using immunocytochemistry in contrast to the homogenous nuclear and cytoplasmic staining in HEK293 cells overexpressing wild-type DJ1 , about 5% of the cells expressing E64D and up to 80% of the cells expressing the recently described L166P mutation displayed a predominant nuclear localization of the mutant DJ1 protein.

7762554

[ "Frequent", "intragenic", "deletion", "of", "the", "P", "gene", " ", "in", "Tanzanian", "patients", "with", "type", "II", "oculocutaneous", "albinism", "(OCA2).", "Type", "II", "oculocutaneous", "albinism", "(OCA2)", "is", "an", "autosomal", "recessive", "disorder", "in", "which", "the", "biosynthesis", "of", "melanin", "pigment", "is", "reduced", "in", "the", "skin,", "hair,", "and", "eyes.", "OCA2,", "which", "results", "from", "mutations", "of", "the", "P", "gene", ",", "is", "the", "most", "frequent", "type", "of", "albinism", "in", "African", "and", "African-American", "patients.", "OCA2", "is", "especially", "frequent", "in", "Tanzania,", "where", "it", "occurs", "with", "an", "incidence", "of", "approximately", "1/1,400.", "We", "have", "identified", "abnormalities", "of", "the", "P", "gene", " ", "in", "each", "of", "13", "unrelated", "patients", "with", "OCA2", "from", "Tanzania.", "One", "of", "these,", "a", "deletion", "of", "exon", "7,", "is", "strongly", "predominant,", "accounting", "for", "approximately", "77%", "of", "mutant", "alleles", "in", "this", "group", "of", "patients." ]

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Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2). Type II oculocutaneous albinism (OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in the skin, hair, and eyes. OCA2, which results from mutations of the P gene , is the most frequent type of albinism in African and African-American patients. OCA2 is especially frequent in Tanzania, where it occurs with an incidence of approximately 1/1,400. We have identified abnormalities of the P gene in each of 13 unrelated patients with OCA2 from Tanzania. One of these, a deletion of exon 7, is strongly predominant, accounting for approximately 77% of mutant alleles in this group of patients.

16395665

[ "Prioritizing", "regions", "of", "candidate", "genes", "for", "efficient", "mutation", "screening.", "The", "availability", "of", "the", "complete", "sequence", "of", "the", "human", "genome", "has", "dramatically", "facilitated", "the", "search", "for", "disease-causing", "sequence", "variations.", "In", "fact,", "the", "rate-limiting", "step", "has", "shifted", "from", "the", "discovery", "and", "characterization", "of", "candidate", "genes", "to", "the", "actual", "screening", "of", "human", "populations", "and", "the", "subsequent", "interpretation", "of", "observed", "variations.", "In", "this", "study", "we", "tested", "the", "hypothesis", "that", "some", "segments", "of", "candidate", "genes", "are", "more", "likely", "than", "others", "to", "contain", "disease-causing", "variations", "and", "that", "these", "segments", "can", "be", "predicted", "bioinformatically.", "A", "bioinformatic", "technique,", "prioritization", "of", "annotated", "regions", "(PAR),", "was", "developed", "to", "predict", "the", "likelihood", "that", "a", "specific", "coding", "region", "of", "a", "gene", "will", "harbor", "a", "disease-causing", "mutation", "based", "on", "conserved", "protein", "functional", "domains", "and", "protein", "secondary", "structures.", "This", "method", "was", "evaluated", "by", "using", "it", "to", "analyze", "710", "genes", "that", "collectively", "harbor", "4,498", "previously", "identified", "mutations.", "Nearly", "50%", "of", "the", "genes", "were", "recognized", "as", "disease-associated", "after", "screening", "only", "9%", "of", "the", "complete", "coding", "sequence.", "The", "PAR", "technique", "identified", "90%", "of", "the", "genes", "as", "containing", "at", "least", "one", "mutation,", "with", "less", "than", "40%", "of", "the", "screening", "resources", "that", "traditional", "approaches", "would", "require.", "These", "results", "suggest", "that", "prioritization", "strategies", "such", "as", "PAR", "can", "accelerate", "disease-gene", "identification", "through", "more", "efficient", "use", "of", "screening", "resources." ]

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Prioritizing regions of candidate genes for efficient mutation screening. The availability of the complete sequence of the human genome has dramatically facilitated the search for disease-causing sequence variations. In fact, the rate-limiting step has shifted from the discovery and characterization of candidate genes to the actual screening of human populations and the subsequent interpretation of observed variations. In this study we tested the hypothesis that some segments of candidate genes are more likely than others to contain disease-causing variations and that these segments can be predicted bioinformatically. A bioinformatic technique, prioritization of annotated regions (PAR), was developed to predict the likelihood that a specific coding region of a gene will harbor a disease-causing mutation based on conserved protein functional domains and protein secondary structures. This method was evaluated by using it to analyze 710 genes that collectively harbor 4,498 previously identified mutations. Nearly 50% of the genes were recognized as disease-associated after screening only 9% of the complete coding sequence. The PAR technique identified 90% of the genes as containing at least one mutation, with less than 40% of the screening resources that traditional approaches would require. These results suggest that prioritization strategies such as PAR can accelerate disease-gene identification through more efficient use of screening resources.

15365989

[ "Novel", "homozygous", "p.E64D", " ", "mutation", "in", "DJ1", " ", "in", "early", "onset", "Parkinson", "disease", "(PARK7).", "Mutations", "in", "the", "parkin", "gene", "have", "been", "identified", "as", "a", "common", "cause", "of", "autosomal", "recessive", "inherited", "Parkinson", "disease", "(PD)", "associated", "with", "early", "disease", "manifestation.", "However,", "based", "on", "linkage", "data,", "mutations", "in", "other", "genes", "contribute", "to", "the", "genetic", "heterogeneity", "of", "early-onset", "PD", "(EOPD).", "Recently,", "two", "mutations", "in", "the", "DJ1", " ", "gene", "were", "described", "as", "a", "second", "cause", "of", "autosomal", "recessive", "EOPD", "(PARK7).", "Analyzing", "the", "PARK7", "PARK7", ").", "Analyzing", "the", "PARK7/", "DJ1", " ", "gene", "in", "104", "EOPD", "patients,", "we", "identified", "a", "third", "mutation,", "c.192G>C", " ", "(", "p.E64D", "),", "associated", "with", "EOPD", "in", "a", "patient", "of", "Turkish", "ancestry", "and", "characterized", "the", "functional", "significance", "of", "this", "amino", "acid", "substitution.", "In", "the", "patient,", "a", "substantial", "reduction", "of", "dopamine", "uptake", "transporter", "(DAT)", "binding", "was", "found", "in", "the", "striatum", "using", "[(18)F]FP-CIT", "and", "PET,", "indicating", "a", "serious", "loss", "of", "presynaptic", "dopaminergic", "afferents.", "His", "sister,", "homozygous", "for", "E64D,", "was", "clinically", "unaffected", "but", "showed", "reduced", "dopamine", "uptake", "when", "compared", "with", "a", "clinically", "unaffected", "brother,", "who", "is", "heterozygous", "for", "E64D", "E64D", ",", "was", "clinically", "unaffected", "but", "showed", "reduced", "dopamine", "uptake", "when", "compared", "with", "a", "clinically", "unaffected", "brother,", "who", "is", "heterozygous", "for", "E64D.", "We", "demonstrate", "by", "crystallography", "that", "the", "E64D", " ", "mutation", "does", "not", "alter", "the", "structure", "of", "the", "DJ1", " ", "protein,", "however", "we", "observe", "a", "tendency", "towards", "decreased", "levels", "of", "the", "mutant", "protein", "when", "overexpressed", "in", "HEK293", "or", "COS7", "cells.", "Using", "immunocytochemistry", "in", "contrast", "to", "the", "homogenous", "nuclear", "and", "cytoplasmic", "staining", "in", "HEK293", "cells", "overexpressing", "wild-type", "DJ1", ",", "about", "5%", "of", "the", "cells", "expressing", "E64D", " ", "and", "up", "to", "80%", "of", "the", "cells", "expressing", "the", "recently", "described", "L166P", " ", "mutation", "displayed", "a", "predominant", "nuclear", "localization", "of", "the", "mutant", "DJ1", " ", "protein." ]

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Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Mutations in the parkin gene have been identified as a common cause of autosomal recessive inherited Parkinson disease (PD) associated with early disease manifestation. However, based on linkage data, mutations in other genes contribute to the genetic heterogeneity of early-onset PD (EOPD). Recently, two mutations in the DJ1 gene were described as a second cause of autosomal recessive EOPD (PARK7). Analyzing the PARK7 PARK7 ). Analyzing the PARK7/ DJ1 gene in 104 EOPD patients, we identified a third mutation, c.192G>C ( p.E64D ), associated with EOPD in a patient of Turkish ancestry and characterized the functional significance of this amino acid substitution. In the patient, a substantial reduction of dopamine uptake transporter (DAT) binding was found in the striatum using [(18)F]FP-CIT and PET, indicating a serious loss of presynaptic dopaminergic afferents. His sister, homozygous for E64D, was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who is heterozygous for E64D E64D , was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who is heterozygous for E64D. We demonstrate by crystallography that the E64D mutation does not alter the structure of the DJ1 protein, however we observe a tendency towards decreased levels of the mutant protein when overexpressed in HEK293 or COS7 cells. Using immunocytochemistry in contrast to the homogenous nuclear and cytoplasmic staining in HEK293 cells overexpressing wild-type DJ1 , about 5% of the cells expressing E64D and up to 80% of the cells expressing the recently described L166P mutation displayed a predominant nuclear localization of the mutant DJ1 protein.