4.5 Article

Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder

期刊

MOLECULAR AUTISM
卷 3, 期 -, 页码 -

出版社

BIOMED CENTRAL LTD
DOI: 10.1186/2040-2392-3-8

关键词

Autism spectrum disorder; Massively parallel DNA sequencing; Rare variation; Evolutionary conservation

资金

  1. NIH/NIMH and Gift Fund [MH076439]
  2. Simons Foundation Autism Research Initiative
  3. Training Program in Human Disease Genetics [1T32MH087977]
  4. PHS [UL1 RR025008]
  5. Clinical and Translational Science Award program
  6. National Institutes of Health
  7. National Center for Research Resource

向作者/读者索取更多资源

Background: Autism spectrum disorder (ASD) is highly heritable, but the genetic risk factors for it remain largely unknown. Although structural variants with large effect sizes may explain up to 15% ASD, genome-wide association studies have failed to uncover common single nucleotide variants with large effects on phenotype. The focus within ASD genetics is now shifting to the examination of rare sequence variants of modest effect, which is most often achieved via exome selection and sequencing. This strategy has indeed identified some rare candidate variants; however, the approach does not capture the full spectrum of genetic variation that might contribute to the phenotype. Methods: We surveyed two loci with known rare variants that contribute to ASD, the X-linked neuroligin genes by performing massively parallel Illumina sequencing of the coding and noncoding regions from these genes in males from families with multiplex autism. We annotated all variant sites and functionally tested a subset to identify other rare mutations contributing to ASD susceptibility. Results: We found seven rare variants at evolutionary conserved sites in our study population. Functional analyses of the three 3 ' UTR variants did not show statistically significant effects on the expression of NLGN3 and NLGN4X. In addition, we identified two NLGN3 intronic variants located within conserved transcription factor binding sites that could potentially affect gene regulation. Conclusions: These data demonstrate the power of massively parallel, targeted sequencing studies of affected individuals for identifying rare, potentially disease-contributing variation. However, they also point out the challenges and limitations of current methods of direct functional testing of rare variants and the difficulties of identifying alleles with modest effects.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据