Human knockout research: new horizons and opportunities

被引：34

作者：

Alkuraya, Fowzan S. ^{[1
,2
]}

机构：

[1] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia

[2] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh, Saudi Arabia

来源：

TRENDS IN GENETICS | 2015年 / 31卷 / 02期

关键词：

loss of function; autozygome; evolution; druggable targets; adaptation; RECENT POSITIVE SELECTION; OF-FUNCTION VARIANTS; SUSCEPTIBILITY LOCI; CROHNS-DISEASE; LOW-FREQUENCY; HUMAN GENOME; RESISTANCE; IDENTIFICATION; ASSOCIATION; MUTATIONS;

D O I：

10.1016/j.tig.2014.11.003

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Although numerous approaches have been pursued to understand the function of human genes, Mendelian genetics has by far provided the most compelling and medically actionable dataset. Biallelic loss-of-function (LOF) mutations are observed in the majority of autosomal recessive Mendelian disorders, representing natural human knockouts and offering a unique opportunity to study the physiological and developmental context of these genes. The restriction of such context to 'disease' states is artificial, however, and the recent ability to survey entire human genomes for biallelic LOF mutations has revealed a surprising landscape of knockout events in 'healthy' individuals, sparking interest in their role in phenotypic diversity beyond disease causation. As I discuss in this review, the potentially wide implications of human knockout research warrant increased investment and multidisciplinary collaborations to overcome existing challenges and reap its benefits.

引用

页码：108 / 115

页数：8

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