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新加坡华人人群中5q31 - q33区域哮喘候选基因的连锁不平衡模式。

Linkage disequilibrium pattern in asthma candidate genes from 5q31-q33 in the Singapore Chinese population.

作者信息

Parate Pallavi N, Wang De Yun, Chew Fook Tim

机构信息

Department of Biological Sciences, National University of Singapore, Singapore.

出版信息

Ann Hum Genet. 2010 Mar;74(2):137-45. doi: 10.1111/j.1469-1809.2009.00558.x. Epub 2010 Jan 8.

Abstract

Studies have shown linkage between microsatellite markers from the chromosome 5q31-q33 region with asthma, atopy and total IgE levels in the Singapore Chinese population. However, subsequent case-control studies failed to show association between the polymorphisms in the candidate genes from this region and asthma or related phenotypes. In this study, we investigated 20 asthma candidate genes from this region for all possible informative polymorphisms within our population, linkage disequilibrium (LD) structure and tagging SNP transferability from HapMap populations. We re-sequenced these genes and identified 267 polymorphisms including 26 insertion-deletions, four microsatellite markers and 237 single nucleotide polymorphisms. The region contained 17 distinct LD blocks with the largest within the serine peptidase inhibitor kazal type 5 (SPINK5) gene spanning 23 kb. Of the 267 polymorphisms identified, 40% are represented in HapMap Han Chinese from Beijing and 29% in Han Chinese from Denver. 72% of the polymorphisms can be represented by tagged SNPs from the HapMap Beijing Han Chinese population and are highly correlated in terms of minor allele frequencies and LD structure. Our data suggest that although the HapMap Han Chinese population from Beijing is very similar to the Singapore Chinese population, this similarity is insufficient to account for up to 28% of the polymorphisms in the local population.

摘要

研究表明,在新加坡华人人群中,5号染色体q31 - q33区域的微卫星标记与哮喘、特应性和总IgE水平之间存在连锁关系。然而,随后的病例对照研究未能显示该区域候选基因的多态性与哮喘或相关表型之间存在关联。在本研究中,我们调查了该区域的20个哮喘候选基因,以寻找我们人群中所有可能的信息性多态性、连锁不平衡(LD)结构以及来自HapMap人群的标签SNP转移性。我们对这些基因进行了重测序,共鉴定出267个多态性位点,包括26个插入缺失、4个微卫星标记和237个单核苷酸多态性。该区域包含17个不同的LD块,其中最大的位于丝氨酸蛋白酶抑制剂Kazal 5型(SPINK5)基因内,跨度为23 kb。在鉴定出的267个多态性位点中,40%在北京的HapMap汉族人群中出现,29%在丹佛的汉族人群中出现。72%的多态性位点可以由北京汉族人群的HapMap标签SNP代表,并且在次要等位基因频率和LD结构方面高度相关。我们的数据表明,尽管北京的HapMap汉族人群与新加坡华人人群非常相似,但这种相似性不足以解释当地人群中高达28%的多态性。

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