最近在一篇综述文章中看到对Gene constraint 的描述，

文章中给的解释为

Using population-scale measurements of variant density and allele frequencies, multiple

groups have developed statistical models of gene-wide constraint that model the tolerance of a gene to amino acid-changing or loss-of-function (LOF) variation relative to all other genes in the human genome。这里文章还举了个例子：

RVIS(the Residual Variation Intolerance Score ) : Use ~6,500 exomes from the NHLBI

Exome Sequencing Project and a linear model comparing the number of common functional variants observed in a gene against the total number of variants observed in the gene。（详见附件）

1，有哪位了解Gene constraint 分析，可以抽空给科普一下么？十分感谢

2. RVIS这种耐受性分析与目前临床常用的SIFT、MutationTaster软件对突变有害性预测有什么不一样，之前了解的是RVIS好像是对基因进行排序的，而SIFT和MutationTaster等好像是对变异进行评估的，是这样么？RVIS在目前遗传病研究中应用的多么？通常怎么应用的呢？十分感谢

• 10.1038@nrg.2017.52 .pdf(823.89k)