期刊
SCIENCE
卷 362, 期 6419, 页码 1161-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aar6731
关键词
-
资金
- Health Innovation Challenge Fund [HICF-I009-003]
- Research Fellowship at St John's College, Cambridge
- National Institute for Health Research Academic Clinical Fellowship
- MRC [MC_UU_00007/3] Funding Source: UKRI
We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, owing to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.
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。
推荐
暂无数据