Abstract:
:Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Emond MJ,Louie T,Emerson J,Zhao W,Mathias RA,Knowles MR,Wright FA,Rieder MJ,Tabor HK,Nickerson DA,Barnes KC,National Heart, Lung, and Blood Institute (NHLBI) GO Exome Sequencing Project.,Lung GO.,Gibson RL,Bamshad MJdoi
10.1038/ng.2344subject
Has Abstractpub_date
2012-07-08 00:00:00pages
886-9issue
8eissn
1061-4036issn
1546-1718pii
ng.2344journal_volume
44pub_type
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