Settling the score: variant prioritization and Mendelian disease

被引：163

作者：

Eilbeck, Karen ^{[1
]}

Quinlan, Aaron ^{[1
,2
]}

Yandell, Mark ^{[2
]}

机构：

[1] Univ Utah, Sch Med, Dept Biomed Informat, 421 Wakara Way,Suite 120, Salt Lake City, UT 84108 USA

[2] Univ Utah, Sch Med, Dept Human Genet, Eccles Inst Human Genet, 15 S 2030 E, Salt Lake City, UT 84112 USA

来源：

NATURE REVIEWS GENETICS | 2017年 / 18卷 / 10期

关键词：

AMINO-ACID SUBSTITUTIONS; OF-FUNCTION VARIANTS; SEQUENCE VARIANTS; GENE DISCOVERY; GENOME; ASSOCIATION; IDENTIFICATION; PHENOTYPE; FRAMEWORK; MUTATION;

D O I：

10.1038/nrg.2017.52

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

When investigating Mendelian disease using exome or genome sequencing, distinguishing disease-causing genetic variants from the multitude of candidate variants is a complex, multidimensional task. Many prioritization tools and online interpretation resources exist, and professional organizations have offered clinical guidelines for review and return of prioritization results. In this Review, we describe the strengths and weaknesses of widely used computational approaches, explain their roles in the diagnostic and discovery process and discuss how they can inform (and misinform) expert reviewers. We place variant prioritization in the wider context of gene prioritization, burden testing and genotype-phenotype association, and we discuss opportunities and challenges introduced by whole-genome sequencing.

引用

页码：599 / 612

页数：14

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