Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families.
Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families.
复制标题
DOI：
10.1038/s41598-017-06033-1
复制
发表时间：
2017-07-18
影响因子：
4.6
通讯作者：
Al Tassan N
中科院分区：
文献类型：
--
作者：
Al-Mubarak B;Abouelhoda M;Omar A;AlDhalaan H;Aldosari M;Nester M;Alshamrani HA;El-Kalioby M;Goljan E;Albar R;Subhani S;Tahir A;Asfahani S;Eskandrani A;Almusaiab A;Magrashi A;Shinwari J;Monies D;Al Tassan N
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，具有遗传和临床异质性。新生和遗传性罕见变异的相互作用在ASD的发展中被怀疑。在这里，我们应用全外显子组测序（WES）对19个来自沙特自闭症孤独症家庭的三人组。我们开发了一种分析管道，可以捕获预测有害的从头和遗传的罕见变异。在17个三重奏中共检测到47个独特的罕见变异，其中38个是新发现的。大多数是常染色体隐性遗传或X连锁。我们的管道发现了15个ASD候选基因的变体，其中包括5个（GLT8D1，HTATSF 1，OR6C65，ITIH 6和DDX 26 B），这些基因在任何人类疾病中都没有报道过。其余的变异发生在以前与ASD或其他神经系统疾病相关的基因中。例子包括SUMF 1，KDM5B和MXRA5（已知ASD基因），PRODH 2和KCTD 21（涉及精神分裂症），以及USP9X和SMS（涉及智力残疾）。与预期和先前的研究一致，本文涉及的大多数基因富集用于与神经元功能有关的生物过程。我们的研究结果强调了ASD遗传结构的私有性和异质性，即使在具有高血缘关系的人群中也是如此。
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with genetic and clinical heterogeneity. The interplay of de novo and inherited rare variants has been suspected in the development of ASD. Here, we applied whole exome sequencing (WES) on 19 trios from singleton Saudi families with ASD. We developed an analysis pipeline that allows capturing both de novo and inherited rare variants predicted to be deleterious. A total of 47 unique rare variants were detected in 17 trios including 38 which are newly discovered. The majority were either autosomal recessive or X-linked. Our pipeline uncovered variants in 15 ASD-candidate genes, including 5 (GLT8D1, HTATSF1, OR6C65, ITIH6 and DDX26B) that have not been reported in any human condition. The remaining variants occurred in genes formerly associated with ASD or other neurological disorders. Examples include SUMF1, KDM5B and MXRA5 (Known-ASD genes), PRODH2 and KCTD21 (implicated in schizophrenia), as well as USP9X and SMS (implicated in intellectual disability). Consistent with expectation and previous studies, most of the genes implicated herein are enriched for biological processes pertaining to neuronal function. Our findings underscore the private and heterogeneous nature of the genetic architecture of ASD even in a population with high consanguinity rates.
登录
查看更多内容
影响因子：
1.6
作者：
El Mouzan MI;Al Salloum AA;Al Herbish AS;Qurachi MM;Al Omar AA
通讯作者：
Al Omar AA
影响因子：
12.3
作者：
Saudi Mendeliome Group
通讯作者：
Saudi Mendeliome Group
影响因子：
14.9
作者：
Basu SN;Kollu R;Banerjee-Basu S
通讯作者：
Banerjee-Basu S
影响因子：
4.3
作者：
Bendl J;Musil M;Štourač J;Zendulka J;Damborský J;Brezovský J
通讯作者：
Brezovský J
影响因子：
5.8
作者：
Filleur S;Hirsch J;Wille A;Schön M;Sell C;Shearer MH;Nelius T;Wieland I
通讯作者：
Wieland I