在欧洲人群中，常染色体隐性致病性变异的景观揭示了表型特异性效应。
The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects.
机构信息
Braun School of Public Health and Community Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel; Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
Department of Human Genetics and Donders Center for Neuroscience, Radboud University Medical Centre, Nijmegen 6525 GA, the Netherlands.
出版信息
Am J Hum Genet. 2021 Apr 1;108(4):608-619. doi: 10.1016/j.ajhg.2021.03.004. Epub 2021 Mar 18.
Abstract
The number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6,447 exome sequences of healthy, genetically unrelated Europeans of two distinct ancestries, we estimate that every individual is a carrier of at least 2 pathogenic variants in currently known autosomal-recessive (AR) genes and that 0.8%-1% of European couples are at risk of having a child affected with a severe AR genetic disorder. This risk is 16.5-fold higher for first cousins but is significantly more increased for skeletal disorders and intellectual disabilities due to their distinct genetic architecture.
摘要
目前，人们还不知道在全基因组范围内，各种疾病的隐性等位基因的数量和分布情况。基于来自两个不同祖先的 6447 个健康的、遗传上无关的欧洲个体的外显子组序列，我们估计每个人至少携带目前已知的常染色体隐性（AR）基因中的 2 个致病性变异，并且 0.8%-1%的欧洲夫妇有生育患有严重 AR 遗传疾病的孩子的风险。这种风险对于表亲来说要高 16.5 倍，但由于其独特的遗传结构，对于骨骼疾病和智力残疾的风险则显著增加。
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