哮喘联盟

   摘要：
   哮喘是复杂的基因-基因以及基因-环境的相互作用引起的。大多数哮喘基因在种群间是不可复制的，可能是由于这些基因的流行病学差异。我们这项病例对照和新一代测序技术联合的研究显示，中国人和其他种群间单核苷酸多态性(SNPs)以及单倍型块哮喘基因频率存在众多差异。本研究的SNPs中将近一半的次要等位基因频率在香港南部的中国受试者中与欧洲白种人、非洲人或后两者之间相差0.2或更多。因为在中国受试者中尚无哮喘全组基因的相关研究，我们不能确定近期基于联合的全基因组相关研究的基因组结果是否适用于我们的人群。另外，在24例健康香港儿童中跨越每十个哮喘位点的100-kb区域使用罗氏454焦磷酸测序。对于17q21轨迹，根据千人基因组项目在香港受试者和6个族群中224个普通的单核苷酸多态性，在单倍体结构中有实质性差异。在香港人中形成了16个主要是小的单倍型块，然而在北京汉族以及中欧受试者中确定了6个单倍型块，在波多黎各和非洲约鲁巴受试者中分别确定了11个和19个。总之，中国人和其他族群间在哮喘基因等位基因频率和哮喘位点的单倍体结构方面存在差异。在种群间基因相关复制标记SNPs的选择中应重视这些序列变异。
 

（林江涛 审校）
JAllergyClinImmunol.2013Nov1.pii:S0091-6749(13)01445-0.doi:10.1016/j.jaci.2013.09.018. [Epub ahead of print]

 

Differences in asthma genetics between Chinese and other populations.
 

Leung TF, Ko FW, Sy HY, Tsui SK, Wong GW.
 

Abstract
Asthma is caused by complex gene-gene and gene-environment interactions. Most asthma genes are not replicable across populations, which is possibly because of differences in the epidemiology of these genes. Our case-control association and next-generation sequencing studies revealed substantial discrepancies in the frequencies of single nucleotide polymorphisms (SNPs) and haplotype blocks for asthma genes between Chinese and other populations. The minor allele frequencies for nearly half of our studied SNPs differed by 0.2 or greater between southern Chinese subjects in Hong Kong and European white populations, African populations, or both. Because genome-wide association studies for asthma have not been performed in Chinese subjects, we cannot tell whether the genomic findings of recent consortium-based genome-wide association studies are applicable to our population. In addition, our group performed Roche 454 pyrosequencing on a 100-kb area spanning each of 10 asthma loci in 24 healthy Hong Kong children. For the 17q21 locus, there was substantial variation in the haplotype structures that were constructed from 224 common SNPs among Hong Kong subjects and 6 ethnic groups under the 1000 Genomes Project. Sixteen mostly small haplotype blocks were formed in Hong Kong, whereas 6 haplotype blocks were identified in Han Chinese in Beijing and central European subjects and 11 and 19 blocks were identified in Puerto Rican and Yoruba African subjects. In conclusion, differences in allele frequencies of asthma genes and haplotype structures of asthma loci are found between Chinese subjects and other ethnic groups. These sequence variations must be considered during the selection of tagging SNPs for replicating genetic associations between populations.
 

JAllergyClinImmunol.2013Nov1.pii:S0091-6749(13)01445-0.doi:10.1016/j.jaci.2013.09.018. [Epub ahead of print]