患有囊腫性纖維化的個體患者具有較高的綠膿桿菌感染風險，而綠膿桿菌感染又與長期性肺部疾病加重和存活率降低有關(guān)。最新一期《自然—遺傳學》(nature genetics )上的一項報告解析出若干與綠膿桿菌感染癥的易感性有關(guān)的遺傳變異,。
為了鑒定出影響綠膿桿菌感染風險的宿主遺傳因子，Michael Bamshad,、 Mary Emond等人使用了一種極端表現(xiàn)型研究設(shè)計方案,，選擇那些處于表現(xiàn)型分布兩端的患者，并結(jié)合了外顯子測序手段,。作為美國國立心肺血液研究所（NHLBI）的外顯子測序計劃（ESP）的一部分,，此次研究對43名初步感染綠膿桿菌的患者以及48名從未感染過綠膿桿菌的年長患者進行了外顯子測序。結(jié)果發(fā)現(xiàn),，DCTN4中的數(shù)個變異與腫囊性纖維化患者體內(nèi)的綠膿桿菌的首次空氣傳染,、慢性感染以及黏液型綠膿桿菌存在關(guān)聯(lián)。他們繼續(xù)對696名腫囊性纖維化患者進行檢測,，驗證了上述發(fā)現(xiàn),。（生物谷Bioon.com）
doi：10.1038/ng.2344
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Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis
Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders1. 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 large2. 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 alleles3. 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.
