Nature medicine：自闭症谱系障碍家庭全基因组测序

           

2015年2月2日讯 /生物谷BIOON/ –近日，国际生物学顶尖期刊nature medicine在线刊登了加拿大科学家的一项最新研究成果，他们通过对85个有两个自闭症谱系障碍（ASD）孩子的四成员家庭和170个患有ASD的个体进行了全基因组测序，发现在ASD疾病中存在大量遗传异质性。根据他们的实验结果，在研究和临床中应用全基因组测序诠释遗传和非遗传性易感突变是非常必要的。

 

ASD是一种遗传异质性疾病，已经有许多证据证明了ASD在基因组上的易感位点。之前有科学家应用基因芯片和外显子测序对6个有单个自闭症谱系障碍孩子的家庭进行了遗传分析，也预测了少量可导致障碍发生的基因。在本文中，Ryan K C Yuen等人对85个有两个自闭症谱系障碍（ASD）孩子的四成员家庭和170个患有ASD的个体进行了全基因组测序，生成了一个包含所有类型基因突变（包括非编码突变）以及相关表型的综合数据资源，同时发现ASD具有明显的家族特性。通过检验之前报道的与ASD和其他类型神经发育障碍有关的单核苷酸和结构突变，研究人员发现约有69.4%受到影响的同家庭兄弟姐妹携带不同的ASD相关突变。这些包含不同ASD相关突变的兄弟姐妹比那些携带相同风险基因突变的人更具有临床变异性。

 

综上所述，该文章作者利用全基因组测序的方法分析了ASD患病人群，发现在ASD疾病中存在大量遗传异质性，并且生成了一个包含ASD基因突变和表型的数据库资源。这项研究表明在研究和临床中应用全基因组测序诠释遗传和非遗传易感突变是非常必要的。（生物谷Bioon.com）

 

 

 

Whole-genome sequencing of quartet families with autism spectrum disorder

 

Ryan K C Yuen, Bhooma Thiruvahindrapuram, Daniele Merico, Susan Walker, Kristiina Tammimies, Ny Hoang, Christina Chrysler, Thomas Nalpathamkalam, Giovanna Pellecchia, Yi Liu, Matthew J Gazzellone, Lia D’Abate, Eric Deneault, Jennifer L Howe,Richard S C Liu, Ann Thompson, Mehdi Zarrei, Mohammed Uddin, Christian R Marshall,Robert H Ring, Lonnie Zwaigenbaum, Peter N Ray, Rosanna Weksberg, Melissa T Carter,Bridget A Fernandez, Wendy Roberts, Peter Szatmari & Stephen W Scherer

 

Autism spectrum disorder (ASD) is genetically heterogeneous, with evidence for hundreds of susceptibility loci. Previous microarray and exome-sequencing studies have examined portions of the genome in simplex families (parents and one ASD-affected child) having presumed sporadic forms of the disorder. We used whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD, to generate a comprehensive data resource encompassing all classes of genetic variation (including noncoding variants) and accompanying phenotypes, in apparently familial forms of ASD. By examining de novo and rare inherited single-nucleotide and structural variations in genes previously reported to be associated with ASD or other neurodevelopmental disorders, we found that some (69.4%) of the affected siblings carried different ASD-relevant mutations. These siblings with discordant mutations tended to demonstrate more clinical variability than those who shared a risk variant. Our study emphasizes that substantial genetic heterogeneity exists in ASD, necessitating the use of WGS to delineate all genic and non-genic susceptibility variants in research and in clinical diagnostics.