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对爱尔兰人群进行涉及癫痫和其他复杂疾病的大规模基因图谱研究评估。

An assessment of the Irish population for large-scale genetic mapping studies involving epilepsy and other complex diseases.

作者信息

O'Dushlaine Colm T, Dolan Ciara, Weale Michael E, Stanton Alice, Croke David T, Kalviainen Reetta, Eriksson Kai, Kantanen Anne-Mari, Gibson Rachel A, Hosford David, Sisodiya Sanjay M, Gill Michael, Corvin Aiden P, Morris Derek W, Delanty Norman, Cavalleri Gianpiero L

机构信息

Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Ireland.

出版信息

Eur J Hum Genet. 2008 Feb;16(2):176-83. doi: 10.1038/sj.ejhg.5201938. Epub 2007 Oct 31.

Abstract

The recent completion of the International HapMap Project has rapidly advanced our understanding of linkage disequilibrium (LD) in the human genome. Today, tagging SNPs (tSNPs) can be quickly and easily selected and consequently HapMap data are regularly applied to both small- and large-scale genetic mapping studies. However, to correctly interpret the application of HapMap-derived tSNPs in a genetic mapping study, an understanding of how well HapMap data represents LD in the study population is critical. The Irish population had not previously been characterised in this way. Here, we do so using a set of 4424 SNPs selected from 279 candidate genes for epilepsy genotyped across 1118 healthy individuals from the Irish, British, Finnish and Australian populations. By considering the Irish population alongside surrounding European populations, our results confirm that the HapMap European-derived population accurately estimates patterning of LD in European descent populations. The Irish population appears notably well matched to the European HapMap population, and is markedly similar to the neighbouring British population. Although we were unable to detect significant substructure within the Irish population (a favourable result for genetic mapping), methods for controlling stratification should always be incorporated. This analysis therefore confirms that the genetic architecture of the Irish population is well suited to the study of complex traits and that tSNPs selected using the HapMap data can be confidently applied to the Irish population.

摘要

国际人类基因组单体型图计划(International HapMap Project)最近的完成,迅速增进了我们对人类基因组中连锁不平衡(LD)的理解。如今,可以快速且轻松地选择标签单核苷酸多态性(tSNP),因此,人类基因组单体型图数据经常应用于小规模和大规模的基因定位研究。然而,要正确解释源自人类基因组单体型图的tSNP在基因定位研究中的应用,了解人类基因组单体型图数据在研究人群中对LD的代表程度至关重要。爱尔兰人群此前尚未以这种方式进行特征描述。在此,我们使用从279个癫痫候选基因中选出的一组4424个单核苷酸多态性,对来自爱尔兰、英国、芬兰和澳大利亚人群的1118名健康个体进行基因分型。通过将爱尔兰人群与周边欧洲人群一并考虑,我们的结果证实,源自人类基因组单体型图欧洲人群的数据能够准确估计欧洲血统人群中的LD模式。爱尔兰人群似乎与欧洲人类基因组单体型图人群特别匹配,并且与邻近的英国人群显著相似。尽管我们未能在爱尔兰人群中检测到显著的亚结构(这对基因定位来说是个有利结果),但控制分层的方法仍应始终纳入考虑。因此,这项分析证实,爱尔兰人群的遗传结构非常适合复杂性状的研究,并且使用人类基因组单体型图数据选择的tSNP可以放心地应用于爱尔兰人群。

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