Copy number variation prevalence in known asthma genes and their impact on asthma susceptibility.
Copy number variation prevalence in known asthma genes and their impact on asthma susceptibility.
复制标题
DOI：
10.1111/cea.12060
复制
发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Raby BA
中科院分区：
文献类型：
--
作者：
Rogers AJ;Chu JH;Darvishi K;Ionita-Laza I;Lehmann H;Mills R;Lee C;Raby BA
遗传学研究已经发现了许多与哮喘相关的基因，然而这些研究几乎完全集中在单核苷酸多态(SNPs)上，而几乎忽略了另一种非常普遍的遗传变异形式：拷贝数变异(CNV)。调查以前与哮喘相关的基因中CNV的患病率，并评估CNV是否代表这些座位上的功能性哮喘易感变异。我们使用竞争性基因组杂交(CGH)阵列对383个参加儿童哮喘管理计划(CAMP)的哮喘三人组进行了基因分型，该阵列旨在询问20,092个CNV。为了确保对所有潜在的哮喘候选基因的全面评估，我们有目的地使用了自由的哮喘基因纳入标准，结果考虑了270个以前与哮喘有关的候选基因。我们使用FBAT-CNV进行统计检验。哮喘候选基因的拷贝数变异很普遍，21%的测试基因位于69个CNV中的一个附近或之内。在6个例子中，完整的候选基因序列位于CNV边界内。平均而言，哮喘先证者携带6个哮喘候选CNV(范围1-29)。然而，绝大多数识别出的CNV是罕见的(5%)，而且在统计学上与哮喘无关。在NOS1和SERPINA3附近观察到2个CNV与哮喘有关的适度证据。连锁不平衡分析表明，CNV效应不太可能解释先前检测到的SNP与哮喘的关联。虽然相当大比例的哮喘易感基因含有多态的CNV，但这些变异中的大多数并不会增加哮喘的风险。CNV和哮喘相关SNPs之间缺乏连锁不平衡(LD)表明，这些CNV不太可能代表导致大多数已知哮喘关联的功能变异。
Genetic studies have identified numerous genes reproducibly associated with asthma, yet these studies have focused almost entirely on single nucleotide polymorphisms (SNPs), and virtually ignored another highly prevalent form of genetic variation: Copy Number Variants (CNVs). To survey the prevalence of CNVs in genes previously associated with asthma, and to assess whether CNVs represent the functional asthma-susceptibility variants at these loci. We genotyped 383 asthmatic trios participating in the Childhood Asthma Management Program (CAMP) using a competitive genomic hybridization (CGH) array designed to interrogate 20,092 CNVs. To ensure comprehensive assessment of all potential asthma candidate genes, we purposely used liberal asthma gene inclusion criteria, resulting in consideration of 270 candidate genes previously implicated in asthma. We performed statistical testing using FBAT-CNV. Copy number variation in asthma candidate genes was prevalent, with 21% of tested genes residing near or within one of 69 CNVs. In 6 instances, the complete candidate gene sequence resides within the CNV boundaries. On average, asthmatic probands carried 6 asthma-candidate CNVs (range 1–29). However, the vast majority of identified CNVs were of rare frequency (< 5%), and were not statistically associated with asthma. Modest evidence for association with asthma was observed for 2 CNVs near NOS1 and SERPINA3. Linkage disequilibrium analysis suggests that CNV effects are unlikely to explain previously detected SNP associations with asthma. Although a substantial proportion of asthma-susceptibility genes harbor polymorphic CNVs, the majority of these variants do not confer increased asthma risk. The lack of linkage disequilibrium (LD) between CNVs and asthma-associated SNPs suggests that these CNVs are unlikely to represent the functional variant responsible for most known asthma associations.
登录
查看更多内容
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
56.9
作者：
Bailey, JA;Gu, ZP;Eichler, EE
通讯作者：
Eichler, EE
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
27.4
作者：
McKinney, C.;Merriman, M. E.;Merriman, T. R.
通讯作者：
Merriman, T. R.
影响因子：
30.8
作者：
Barnes, Chris;Plagnol, Vincent;Fitzgerald, Tomas;Redon, Richard;Marchini, Jonathan;Clayton, David;Hurles, Matthew E.
通讯作者：
Hurles, Matthew E.