bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk
Authors: Schabath Matthew B. , Spitz Margaret R. , Delclos George L. , Gunn Gary B. , Whitehead Lawrence W. , Wu Xifeng 
Published: October 2002

AbstractBackgroundAs observed in tobacco‐associated carcinogenesis, genetic factors such as the polymorphic metabolic/oxidative enzyme myeloperoxidase (MPO) could modulate individual susceptibility to asbestos‐associated carcinogenesis.MethodsRFLP‐PCR analysis identified the MPO genotypes in 375 Caucasian lung cancer cases and 378 matched controls. An epidemiological interview elicited detailed information regarding smoking history and occupational history and exposures.ResultsAsbestos exposure was associated with a significantly elevated risk estimate (OR = 1.45; 95% CI 1.04–2.02). On stratified analysis, we found the MPO genotypes modified the effect of asbestos exposure on lung cancer risk. Specifically, G/G carriers who were exposed to asbestos had an odds ratio (OR) of 1.72 (95% CI; 1.09–2.66), while A‐allele carriers (G/A + A/A) exposed to asbestos exhibited a reduced OR of 0.89 (95% CI; 0.56–1.44). The OR was further reduced to 0.73 (0.49–1.06) for A‐allele carriers not exposed to asbestos. A similar trend was observed for the joint effects between the MPO genotypes and pack‐years smoking. Next, all three risk factors (MPO genotypes, asbestos exposure, and smoking) were analyzed simultaneously for joint effects. Heavy smokers with the G/G genotype and a history of asbestos exposure demonstrated a statistically significant elevated risk estimate (OR = 2.19; 95% CI 1.16–4.11), while the A‐allele carriers with the same exposure profile were at a lower risk for lung cancer (OR = 1.18; 95% CI 0.58–2.38). The A‐allele genotypes demonstrated similar protective effects for the other three exposure profiles.ConclusionsFor a similar level of exposure to established carcinogens, individuals with the MPO A‐allele genotypes appear to have a reduced risk of lung cancer. Am. J. Ind. Med. 42:29–37, 2002. © 2002 Wiley‐Liss, Inc.
Multicultural genetic counseling: Then, now, and in the 21st century
Authors: Ota Wang Vivian 
Published: October 2002

AbstractScholars, educators, and practitioners have argued that racial–cultural issues are obstacles for those seeking genetic counseling. When available, cross‐cultural genetic counseling has focused on simplistic knowledge of client health beliefs and cultural customs, professional cultures, and biased theoretical models as reasons for failure to create realistic knowledge of members of racial–cultural groups in the United States. Recognizing the importance of meeting the needs for all who seek genetic counseling services, genetic counselors have been providing direction in cross‐cultural genetic counseling research, practice, training, and developing competency, ethical, and professional guidelines. However, emanating from a cultural pluralism perspective, cross‐cultural genetic counseling has often resulted in homogenized group stereotypes without attention to intragroup variation and individual differences. A transition from cross‐cultural towards multicultural genetics shifts from culture‐specific group norms to an integrated social, historical, psychological, and political perspective. By valuing the process of personal and professional racial–cultural identity development, the evolution from cross‐cultural to multicultural genetic counseling that has occurred within the past quarter century is discussed. © 2001 Wiley‐Liss, Inc.
Empowering primary care health professionals in medical genetics: How soon? How fast? How far?
Authors: Greendale Karen , Pyeritz Reed E. 
Published: October 2002

AbstractApplications of genetics to the practices of medicine and public health are important today and will only become more compelling as our understanding of the human genome evolves. Because of a perceived lack of medical genetics professionals, it is generally believed that primary health care providers (PCPs) will need to assume prominent roles in delivering clinical genetics services. However, a number of studies indicate that most PCPs are neither well enough educated in genetics nor interested enough in becoming so to effectively contribute. Those who advocate empowering PCPs must be aware of potential problems with any approach thus far suggested for achieving this goal. Moreover, any analysis of this model must consider the potential ramifications for medical genetics professionals, patients, and families. In this article, we explore some of the unique features of the culture of medical genetics services and service providers. We discuss how important this culture is to clinical outcomes and the likelihood that its positive attributes would be preserved in a PCP model of medical genetics service delivery. © 2001 Wiley‐Liss, Inc.
Impact of genetic and non‐genetic factors in type 1 diabetes
Authors: Hawa Mohammed Iqbal , Beyan Huriya , Buckley Lisa Rebecca , Leslie Richard David Graham 
Published: October 2002

AbstractType 1 insulin‐dependent diabetes is due to destruction of the insulin secreting cells of the islets of Langerhans. The disease is caused by non‐genetic, probably environmental, factors operating in a genetically susceptible host to initiate a destructive immune process. These unknown environmental factors may operate over a limited period either in early or later and to a variable degree, playing a particularly substantial role in adults. The environment then induces an immune process associated with destruction of the islet β cell that can be detected in early life and persists up to disease onset. Apart from an association with the insulin gene there is no evidence that genes associated with type 1 diabetes, including HLA and CTLA4 influence the targeting of the immune response to the insulin‐secreting cells. The critical period of immune activation is probably short and the process leading to diabetes probably has a long prodrome but of variable duration that determines the age at presentation with clinical disease. The amplification both of this immune response and the destructive process is in part genetically determined, involving HLA genes. The clinical spectrum of the disease process associated with type 1 diabetes is wide, encompassing insulin‐dependence, non‐insulin dependence and even transient impaired glucose tolerance. Type 1 diabetes presenting in adults, in contrast to children, is predominantly determined by non‐genetic factors with a reduced role for protective and susceptibility HLA alleles. Thus, the evidence is that genes involved in genetic susceptibility to type 1 diabetes operate predominantly in children not adults and in both amplify the immune response and the rate of disease progression. © 2002 Wiley‐Liss, Inc.
Genetic analysis of patients with the Saethre‐Chotzen phenotype
Authors: Chun Kathy , Teebi Ahmad S. , Jung Jack H. , Kennedy Shelley , Laframboise Rachel , Meschino Wendy S. , Nakabayashi Kazuhiko , Scherer Stephen W. , Ray Peter N. , Teshima Ikuko 
Published: October 2002

AbstractSaethre‐Chotzen syndrome is a common craniosynostosis syndrome characterized by craniofacial and limb anomalies. Intragenic mutations of the TWIST gene within 7p21 have been identified as a cause of this disorder. There is phenotypic overlap with other craniosynostosis syndromes, and intragenic mutations in FGFR2 (fibroblast growth factor receptor 2) and FGFR3 (fibroblast growth factor receptor 3) have been demonstrated in the other conditions. Furthermore, complete gene deletions of TWIST have also been found in a significant proportion of patients with Saethre‐Chotzen syndrome. We investigated 11 patients clinically identified as having the Saethre‐Chotzen phenotype and 4 patients with craniosynostosis but without a clear diagnosis. Of the patients with the Saethre‐Chotzen phenotype, four were found to carry the FGFR3 P250R mutation, three were found to be heterozygous for three different novel mutations in the coding region of TWIST, and two were found to have a deletion of one copy of the entire TWIST gene. Developmental delay was a distinguishing feature of the patients with deletions, compared to patients with intragenic mutations of TWIST, in agreement with the results of Johnson et al. [1998: Am J Hum Genet 63:1282–1293]. No mutations were found for the four patients with craniosynostosis without a clear diagnosis. Therefore, 9 of our 11 patients (82%) with the Saethre‐Chotzen phenotype had detectable genetic changes in FGFR3 or TWIST. We propose that initial screening for the FGFR3 P250R mutation, followed by sequencing of TWIST and then fluorescence in situ hybridization (FISH) for deletion detection of TWIST, is sufficient to detect mutations in > 80% of patients with the Saethre‐Chotzen phenotype. © 2002 Wiley‐Liss, Inc.
Effect of the APOE‐491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study
Authors: Roks G. , Cruts M. , Houwing‐Duistermaat J.J. , Dermaut B. , Serneels S. , Havekes L.M. , Hofman A. , Breteler M.M.B. , Van Broeckhoven C. , van Duijn C.M. 
Published: October 2002

AbstractThe apolipoprotein E (APOE) gene is involved in lipid transport. A common polymorphism in this gene with the APOE*2, APOE*3, and APOE*4 alleles influences plasma levels of apolipoprotein E and cholesterol. Besides its role in lipid transport, the APOE*4 allele is a genetic risk factor for Alzheimer disease (AD). Recently, a polymorphism in the APOE promoter region was found to be involved in plasma apolipoprotein E levels and was found associated with AD. We studied the effect of this −491A/T promoter polymorphism on plasma apolipoprotein E levels and risk for AD in a population‐based case‐control study. We found that there was a modest but statistically significant effect of the −491A/T polymorphism on plasma apolipoprotein E levels independent of the APOE genotype. The lowest plasma levels were measured for the AA genotype, highest levels for the TT genotype, and intermediate levels for the heterozygotes. There was a small effect of the −491 AA genotype on AD risk that disappeared after adjusting for APOE genotypes. Our data suggest that the −491A/T polymorphism has an APOE genotype‐independent effect on plasma apolipoprotein E levels but no APOE‐independent effect on AD risk. © 2002 Wiley‐Liss, Inc.
Evaluation of FOXP2 as an autism susceptibility gene
Authors: Wassink Thomas H. , Piven Joseph , Vieland Veronica J. , Pietila Jennifer , Goedken Rhinda J. , Folstein Susan E. , Sheffield Val C. 
Published: October 2002

AbstractA mutation in the gene FOXP2 was recently identified as being responsible for a complicated speech and language phenotype in a single large extended pedigree. This gene is of interest to autism because it lies in one of the most consistently linked autism chromosomal regions of interest. We therefore tested this gene for its involvement in autism in a large sample of autism families. We completely sequenced the exon containing the mutation, screened the remaining coding sequence using SSCP technology, and identified and genotyped two novel intronic tetranucleotide repeat polymorphisms that were then analyzed for evidence of linkage and linkage disequilibrium (LD). We identified two families in which heterozygous deletions of a small number of glutamines in a long poly‐glutamine stretch were found in one parent and the autistic probands; no other non‐conservative coding sequence changes were identified. Linkage and LD analyses were performed in 75 affected sibling pair families and in two subgroups of this sample defined by the presence/absence of severe language impairment. One allele appeared to have an opposite pattern of transmission in the language based subgroups, but otherwise the linkage and LD analyses were negative. We conclude that FOXP2 is unlikely to contribute significantly to autism susceptibility. © 2002 Wiley‐Liss, Inc.
Mosaic r(13) resulting in large deletion of chromosome 13q in a newborn female with multiple congenital anomalies
Authors: Lorentz Cindy Pham , Jalal Syed M. , Thompson Dana M. , Babovic‐Vuksanovic Dusica 
Published: October 2002

AbstractA newborn female presented with multiple congenital anomalies including facial dysmorphism, agenesis of the corpus callosum, type I laryngeal cleft, tracheal stenosis, bilaterally small kidneys, segmental vertebral anomalies, extranumerary rib, bilateral hip dislocation, digital anomalies, and growth retardation. Newborn aneuploidy detection (NAD) based on interphase fluorescence in situ hybridization (FISH) indicated monosomy 13 in 47 of 200 (23.5%) peripheral blood cells (normal cutoff 8.5% at 95% CI). The follow‐up banded metaphase‐based analysis of 20 cells revealed a karyotype of 46,XX. The analysis of 30 additional cells revealed one cell to have monosomy 13 and a small ring chromosome. In the abnormal cell line, the ring was positive for whole chromosome paint (wcp) 13 and negative for Rb1 (13q14.3). The ring was detected in 4% of 80 additional metaphases studied by FISH. Therefore, the ring was present in 4% (5/130) of metaphases from peripheral blood. Analysis of buccal cells by FISH indicated the ring was present in 36% of cells. A higher degree of mosaicism (60%) was detected in fibroblast cultures from a skin biopsy. The low‐level mosaicism of ring 13 in metaphase cells from peripheral blood would have been missed if the standard 20 GTL‐banded metaphases had been analyzed. In this case, a preliminary interphase FISH study had indicated monosomy 13 resulting from a large 13q deletion that included the Rb1 locus. This finding initiated the analysis of additional metaphases by GTL‐banding and the analysis of metaphases and interphases by FISH. The clinical presentation of our patient was consistent with reported cases of 13q deletions. In addition, our patient had airway anomalies, including a type I laryngeal cleft and tracheal stenosis, which are previously unreported. © 2002 Wiley‐Liss, Inc.
Childhood‐onset ataxia: Testing for large CAG‐repeats in SCA2 and SCA7
Authors: Mao Rong , Aylsworth Arthur S. , Potter Nicholas , Wilson William G. , Breningstall Galen , Wick Myra J. , Babovic‐Vuksanovic Dusica , Nance Martha , Patterson Marc C. , Gomez Christopher M. , Snow Karen 
Published: October 2002

AbstractInfantile‐ and juvenile‐onset spinal cerebellar ataxia (SCA) is associated with expansion of 130 to more than 200 CAG‐repeats in the SCA2 and SCA7 genes. Routine clinical assays for SCA2 and SCA7, which use polymerase chain reaction (PCR) and denaturing PAGE (polyacrylamide gel electrophoresis), will not reliably detect such large expansions. An assay based on separation of PCR products on an agarose gel, blotting, and hybridization with a (CAG)6 oligonucleotide probe was used to test DNA from individuals more than 10 years of age who had a possible diagnosis of SCA. Among 25 cases, the PCR‐blot assay confirmed the presence of SCA2 expansions between 230 and 500 repeats in four unrelated individuals, but did not detect any cases of extreme expansion in the SCA7 gene. The PCR‐blot assay provides reliable detection of extreme expansion mutations. Routine incorporation of this assay in clinical laboratories may reveal that infantile–juvenile forms of SCA2 and SCA7 are more prevalent than previously recognized. © 2002 Wiley‐Liss, Inc.
Maternal isodisomy for 14q21‐q24 in a man with diabetes mellitus
Authors: Kayashima Tomohiko , Katahira Masahito , Harada Naoki , Miwa Nobutomo , Ohta Tohru , Yoshiura Koh‐ichiro , Matsumoto Naomichi , Nakane Yoshibumi , Nakamura Yusuke , Kajii Tadashi , Niikawa Norio , Kishino Tatsuya 
Published: October 2002

AbstractWe report a 20‐year‐old man with maternal uniparental disomy for chromosome 14 (UPD14) and maturity‐onset diabetes mellitus (DM). He had pre‐ and postnatal growth retardation, developed DM at age 20 years without any autoimmune antibodies, and had a mosaic 45,XY,der(14;14)(q10;q10)[129]/46,XY,+14,der(14;14)(q10;q10)[1] karyotype. Allelotyping using microsatellite markers covering the entire 14q indicated segmental maternal isodisomy for 14q21‐q24 and maternal heterodisomy of the remaining regions of the chromosome. It is thus tempting to speculate that the segmental isodisomy led to reduction to homozygosity for a mutant gene and thus caused his DM, although the possibility of coincidental occurrence of the two events cannot totally be ruled out. Fluorescence in situ hybridization (FISH) analysis using BAC clone probes revealed that the isodisomic segment did not overlap any known IDDM or NIDDM susceptibility loci on chromosome 14, suggesting a novel locus for a subset of DM at the isodisomic segment. © 2002 Wiley‐Liss, Inc.
Difference in disease‐free survival curve and regional distribution according to subtype of spinocerebellar ataxia: A study of 1,286 Japanese patients
Authors: Maruyama Hirofumi , Izumi Yuishin , Morino Hiroyuki , Oda Masaya , Toji Hiromasa , Nakamura Shigenobu , Kawakami Hideshi 
Published: October 2002

AbstractExpansions of trinucleotide repeats have been discovered in spinocerebellar ataxia (SCA) types 1, 2, 6, 7, 12, and 17, Machado‐Joseph disease (MJD/SCA3), and dentatorubropallidoluysian atrophy (DRPLA). However, the frequency of familial SCA in Japan remains unclear. The number of trinucleotide repeats was determined for 1,286 patients. Three hundred and thirty families (523 cases) were autosomal dominant group (A), and 165 families were positive for family history but not autosomal dominant group (B), while the remaining 598 cases were the sporadic group (C). The frequency of SCA subtypes in autosomal dominant group was: 1) 5.5% for SCA1; 2) 2.4% for SCA2; 3) 27.6% for MJD/SCA3; 4) 25.5% for SCA6; 5) 0.3% for SCA17; and 6) 7.3% for DRPLA. Abnormal expansion of SCA12 was not detected. Another 31.5% of the patients in the autosomal dominant group had unknown genetic abnormalities. Within group B, SCA6 was the most prominent and within the sporadic group MJD/SCA3 and SCA6 were the most common subtypes observed. The disease‐free survival curve of SCA6 was different from that of other SCAs and the mean age at onset for SCA6 was found to be later than that of the other types. Regional differences were observed in the relative rate of SCA subtypes. MJD/SCA3 appears more common in the Kanto and Kyushu districts of Japan, whereas SCA6 is most common in the Chugoku district. In order to establish an effective social welfare system for SCA patients, clinical course and regional differences in the prevalence of SCA subtypes must be taken into consideration. © 2002 Wiley‐Liss, Inc.
Evaluation of multiple presenilin 2 SNPs for association with early‐onset sporadic Alzheimer disease
Authors: Howell W. Mathias , Brookes Anthony J. 
Published: October 2002

AbstractThe presenilin genes encode proteins that modify, mediate, or perform similar functions to γ‐secretase, the enzyme responsible for converting amyloid β precursor protein (APP) into beta‐amyloid. Mutations in the presenilin genes cause an increased production of Aβ42, the aberrant form of beta‐amyloid found in the neural plaques of Alzheimer disease patients. Previously reported association studies of presenilin 2 (PSEN2) polymorphisms with early‐onset Alzheimer disease (EOAD) have produced contradictory results. In an effort to resolve these differences, we tested eight single nucleotide polymorphisms in and around the 3′ region of the PSEN2 gene for association with EOAD. An initial set of Scottish EOAD cases (n = 121) and controls (n = 152) was screened using the genotyping method dynamic allele‐specific hybridization (DASH). No significant differences were seen between allele or genotype frequencies of cases and controls. However, when conditioned on the risk allele (ε4) APOE, three polymorphisms showed allelic association with a P value below 0.05. These same polymorphisms were in near 100% linkage disequilibrium with each other (P < 5 × 10−5), and in each, one of the homozygous genotypes was absent in controls but present in the cases. Replication in an independent set of Scottish EOAD cases (n = 84) and controls (n = 173) did not confirm this finding. From this study we find no evidence to suggest that variations in the PSEN2 gene pose as major risk factors for sporadic EOAD. © 2002 Wiley‐Liss, Inc.
Duplication of (2)(q11.1‐q13.2) in a boy with mental retardation and cleft lip and palate: Another clefting gene locus on proximal 2q?
Authors: Riegel Mariluce , Schinzel Albert 
Published: October 2002

AbstractA 4‐year‐old boy with left cleft lip and cleft palate, multiple minor anomalies and developmental delay revealed an abnormal chromosome 2 with enlarged proximal long arm, de novo, in his karyotype. Fluorescence in situ hybridization with a chromosome 2 library and band‐specific YACs confined the duplicated segment to 2q11.1‐q13.2 and indicated a direct tandem duplication due to unbalanced crossover between chromatids. © 2002 Wiley‐Liss, Inc.
Aromatic amino acid hydroxylase genes and schizophrenia
Authors: Chao Helen M. , Richardson Mary Ann 
Published: October 2002

AbstractPhenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) that catalyze the rate‐limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline, and serotonin. Because these neurotransmitter systems have all been implicated in the pathophysiology of schizophrenia, the aromatic amino acid hydroxylases are among the likely candidates for genes associated with schizophrenia. A mutation in the functionally critical tetrahydrobiopterin cofactor binding domain of the PAH gene had been identified in African‐American patients with the diagnosis of schizophrenia, and biochemical analyses suggested that this mutation has physiological consequences related to amine neurotransmitter function. DNA sequencing of the highly conserved cofactor binding domain of the PAH, TH, and TPH genes in African‐American subjects with schizophrenia and unrelated, never mentally ill subjects from the NIMH Schizophrenia Genetics Initiative, was undertaken to assess the concordance of mutant genotype with psychiatric phenotype. The K274E mutation was observed in the PAH gene cofactor binding domain, and several polymorphisms were identified in adjacent intronic regions of the PAH, TH, and TPH genes. All of the genetic variants observed were represented in the schizophrenia group and in the never mentally ill group. Genetic evaluation of the family members of subjects with the PAH K274E mutation showed that all individuals with the K274E mutation also exhibited the PAH L321L polymorphism in the catalytic domain of the PAH enzyme. © 2002 Wiley‐Liss, Inc.