Whole-exome sequencing of a pedigree segregating asthma.
Whole-exome sequencing of a pedigree segregating asthma.
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DOI：
10.1186/1471-2350-13-95
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发表时间：
2012-10-09
影响因子：
--
通讯作者：
Bracken MB
中科院分区：
文献类型：
--
作者：
DeWan AT;Egan KB;Hellenbrand K;Sorrentino K;Pizzoferrato N;Walsh KM;Bracken MB
尽管哮喘的全基因组关联研究取得了成功，但几乎没有明确的因果变异被识别出来，而且这种疾病的遗传性仍有很大一部分有待发现。这种“缺失遗传性”的部分原因可能是被发现与哮喘分离的家族特有的编码变异。为了确定与哮喘分离的家族特异性变异，我们从先前的哮喘研究中招募了一个家庭，作为报告多个哮喘和非哮喘儿童的家庭。我们对所有四名儿童和父母进行了全外显子组测序，并确定了与哮喘分离的编码变异，这些变异在其他变异数据库中没有发现。在两个患病的后代和患病的母亲中发现了10个新的变种，但在未患病的父亲和两个未患病的子女中没有发现。在这10个基因中，有三个基因(PDE4DIP、CBLB和KALRN)的变异基于它们的功能预测分数和先前报道的功能或哮喘相关性而被认为是特别感兴趣的。我们没有发现任何与哮喘分离的常见危险变异，然而，我们确实观察到与非哮喘儿童相比，哮喘儿童哮喘候选基因中新的、非同义变异的数量增加。这是第一份应用外显子组测序来识别哮喘易感变异的报告。尽管只对一个分离哮喘的家族进行了测序，但我们已经在有趣的哮喘候选基因中发现了几个潜在的功能变异。这将为未来的工作提供基础，在这些工作中，将对更多的家族进行测序，以识别聚集在基因内的家族之间的变异。
Despite the success of genome-wide association studies for asthma, few, if any, definitively causal variants have been identified and there is still a substantial portion of the heritability of the disease yet to be discovered. Some of this “missing heritability” may be accounted for by family-specific coding variants found to be segregating with asthma. To identify family-specific variants segregating with asthma, we recruited one family from a previous study of asthma as reporting multiple asthmatic and non-asthmatic children. We performed whole-exome sequencing on all four children and both parents and identified coding variants segregating with asthma that were not found in other variant databases. Ten novel variants were identified that were found in the two affected offspring and affected mother, but absent in the unaffected father and two unaffected offspring. Of these ten, variants in three genes (PDE4DIP, CBLB, and KALRN) were deemed of particular interest based on their functional prediction scores and previously reported function or asthma association. We did not identify any common risk variants segregating with asthma, however, we did observe an increase in the number of novel, nonsynonymous variants in asthma candidate genes in the asthmatic children compared to the non-asthmatic children. This is the first report applying exome sequencing to identify asthma susceptibility variants. Despite having sequenced only one family segregating asthma, we have identified several potentially functional variants in interesting asthma candidate genes. This will provide the basis for future work in which more families will be sequenced to identify variants across families that cluster within genes.
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DOI：
10.4168/aair.2011.3.4.236
发表时间：
2011-10
期刊：
Allergy, asthma & immunology research
影响因子：
--
作者：
Lee SH;Park JS;Park CS
通讯作者：
Park CS
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Sanders, Stephan J.;Murtha, Michael T.;Gupta, Abha R.;Murdoch, John D.;Raubeson, Melanie J.;Willsey, A. Jeremy;Ercan-Sencicek, A. Gulhan;DiLullo, Nicholas M.;Parikshak, Neelroop N.;Stein, Jason L.;Walker, Michael F.;Ober, Gordon T.;Teran, Nicole A.;Song, Youeun;El-Fishawy, Paul;Murtha, Ryan C.;Choi, Murim;Overton, John D.;Bjornson, Robert D.;Carriero, Nicholas J.;Meyer, Kyle A.;Bilguvar, Kaya;Mane, Shrikant M.;Sestan, Nenad;Lifton, Richard P.;Guenel, Murat;Roeder, Kathryn;Geschwind, Daniel H.;Devlin, Bernie;State, Matthew W.
通讯作者：
State, Matthew W.
影响因子：
30.8
作者：
Sanna, Serena;Jackson, Anne U.;Mohlke, Karen L.
通讯作者：
Mohlke, Karen L.