作者
Elinor K Karlsson, Jason B Harris, Shervin Tabrizi, Atiqur Rahman, Ilya Shlyakhter, Nick Patterson, Colm O’Dushlaine, Stephen F Schaffner, Sameer Gupta, Fahima Chowdhury, Alaullah Sheikh, Ok Sarah Shin, Crystal Ellis, Christine E Becker, Lynda M Stuart, Stephen B Calderwood, Edward T Ryan, Firdausi Qadri, Pardis C Sabeti, Regina C LaRocque
发表日期
2013/7/3
期刊
Science translational medicine
卷号
5
期号
192
页码范围
192ra86-192ra86
出版商
American Association for the Advancement of Science
简介
As an ancient disease with high fatality, cholera has likely exerted strong selective pressure on affected human populations. We performed a genome-wide study of natural selection in a population from the Ganges River Delta, the historic geographic epicenter of cholera. We identified 305 candidate selected regions using the composite of multiple signals (CMS) method. The regions were enriched for potassium channel genes involved in cyclic adenosine monophosphate–mediated chloride secretion and for components of the innate immune system involved in nuclear factor κB (NF-κB) signaling. We demonstrate that a number of these strongly selected genes are associated with cholera susceptibility in two separate cohorts. We further identify repeated examples of selection and association in an NF-κB/inflammasome–dependent pathway that is activated in vitro by Vibrio cholerae. Our findings shed light on the …
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EK Karlsson, JB Harris, S Tabrizi, A Rahman… - Science translational medicine, 2013