دورية أكاديمية
أعرض في EDS

Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy.

التفاصيل البيبلوغرافية
العنوان: Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy.
المؤلفون: Heinzen EL; Center for Human Genome Variation, Duke University School of Medicine, Durham, NC 27708, USA. e.heinzen@duke.edu, Depondt C, Cavalleri GL, Ruzzo EK, Walley NM, Need AC, Ge D, He M, Cirulli ET, Zhao Q, Cronin KD, Gumbs CE, Campbell CR, Hong LK, Maia JM, Shianna KV, McCormack M, Radtke RA, O'Conner GD, Mikati MA, Gallentine WB, Husain AM, Sinha SR, Chinthapalli K, Puranam RS, McNamara JO, Ottman R, Sisodiya SM, Delanty N, Goldstein DB
المصدر: American journal of human genetics [Am J Hum Genet] 2012 Aug 10; Vol. 91 (2), pp. 293-302. Date of Electronic Publication: 2012 Aug 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE
أسماء مطبوعة: Publication: 2008- : [Cambridge, MA] : Cell Press
Original Publication: Baltimore, American Society of Human Genetics.
مواضيع طبية MeSH: Epilepsy, Generalized/*genetics , Exome/*genetics , Genetic Predisposition to Disease/*genetics, Base Sequence ; Genome-Wide Association Study ; Genotype ; Humans ; Molecular Sequence Data ; Sequence Alignment ; Sequence Analysis, DNA ; White People/genetics
مستخلص: Idiopathic generalized epilepsy (IGE) is a complex disease with high heritability, but little is known about its genetic architecture. Rare copy-number variants have been found to explain nearly 3% of individuals with IGE; however, it remains unclear whether variants with moderate effect size and frequencies below what are reliably detected with genome-wide association studies contribute significantly to disease risk. In this study, we compare the exome sequences of 118 individuals with IGE and 242 controls of European ancestry by using next-generation sequencing. The exome-sequenced epilepsy cases include study subjects with two forms of IGE, including juvenile myoclonic epilepsy (n = 93) and absence epilepsy (n = 25). However, our discovery strategy did not assume common genetic control between the subtypes of IGE considered. In the sequence data, as expected, no variants were significantly associated with the IGE phenotype or more specific IGE diagnoses. We then selected 3,897 candidate epilepsy-susceptibility variants from the sequence data and genotyped them in a larger set of 878 individuals with IGE and 1,830 controls. Again, no variant achieved statistical significance. However, 1,935 variants were observed exclusively in cases either as heterozygous or homozygous genotypes. It is likely that this set of variants includes real risk factors. The lack of significant association evidence of single variants with disease in this two-stage approach emphasizes the high genetic heterogeneity of epilepsy disorders, suggests that the impact of any individual single-nucleotide variant in this disease is small, and indicates that gene-based approaches might be more successful for future sequencing studies of epilepsy predisposition.
(Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: P30 AG028377 United States AG NIA NIH HHS; RC2 NS070342 United States NS NINDS NIH HHS; RC2NS070344 United States NS NINDS NIH HHS; 084730 United Kingdom WT_ Wellcome Trust; RC2 NS070344 United States NS NINDS NIH HHS; United Kingdom WT_ Wellcome Trust; 1RC2NS070342 United States NS NINDS NIH HHS; T32 GM007754 United States GM NIGMS NIH HHS; RC2 MH089915 United States MH NIMH NIH HHS; RC2MH089915 United States MH NIMH NIH HHS
تواريخ الأحداث: Date Created: 20120807 Date Completed: 20121022 Latest Revision: 20230610
رمز التحديث: 20230610
مُعرف محوري في PubMed: PMC3415540
DOI: 10.1016/j.ajhg.2012.06.016
PMID: 22863189
قاعدة البيانات: MEDLINE
الوصف
تدمد:1537-6605
DOI:10.1016/j.ajhg.2012.06.016