Schmenger Torsten, Diwan Gaurav D, Singh Gurdeep, Apic Gordana, Russell Robert B
BioQuant, Heidelberg University, Heidelberg, Germany.
Heidelberg University Biochemistry Center (BZH), Heidelberg, Germany.
NPJ Genom Med. 2022 Sep 8;7(1):54. doi: 10.1038/s41525-022-00322-z.
The rapid pace with which genetic variants are now being determined means there is a pressing need to understand how they affect biological systems. Variants from healthy individuals have previously been used to study blood groups or HLA diversity and to identify genes that can apparently be nonfunctional in healthy people. These studies and others have observed a lower than expected frequency of homozygous individuals for potentially deleterious alleles, which would suggest that several of these alleles can lead to recessive disorders. Here we exploited this principle to hunt for potential disease variants in genomes from healthy people. We identified at least 108 exclusively heterozygous variants with evidence for an impact on biological function. We discuss several examples of candidate variants/genes including CCDC8, PANK3, RHD and NLRP12. Overall, the results suggest there are many, comparatively frequent, potentially lethal or disease-causing variants lurking in healthy human populations.
如今确定基因变异的速度之快，意味着迫切需要了解它们如何影响生物系统。此前，来自健康个体的变异已被用于研究血型或HLA多样性，并识别那些在健康人身上显然可能无功能的基因。这些研究以及其他研究观察到，潜在有害等位基因的纯合个体频率低于预期，这表明其中一些等位基因可能导致隐性疾病。在此，我们利用这一原理在健康人的基因组中寻找潜在的疾病变异。我们鉴定出至少108个纯为杂合的变异，有证据表明它们对生物功能有影响。我们讨论了几个候选变异/基因的例子，包括CCDC8、PANK3、RHD和NLRP12。总体而言，结果表明在健康人群中潜藏着许多相对常见的、潜在致命或致病的变异。
