A statistical method for predicting classical HLA alleles from SNP data
A statistical method for predicting classical HLA alleles from SNP data
复制标题
DOI：
10.1016/j.ajhg.2007.09.001
复制
发表时间：
2008-01-01
影响因子：
9.8
通讯作者：
McVean, Gil
中科院分区：
文献类型：
--
作者：
Leslie, Stephen;Donnelly, Peter;McVean, Gil
经典 HLA 等位基因的遗传变异是移植成功和对大量传染性和自身免疫性疾病易感性的关键决定因素。然而，涉及经典 I 型和 II 型 HLA 等位基因的大规模研究可能会受到等位基因分型技术成本的限制。尽管最近的研究表明一些常见的 HLA 等位基因可以用少量标记进行标记，但基于 1,2 SNP 的标记并不能提供预测 HLA 等位基因的完整解决方案。我们开发了一种新的统计方法，利用该区域内的 SNP 变异来预测关键 I 类（HLA-A、HLA-B 和 HLA-C）和 II 类（HLA-DRB1、HLA-DQA1 和 HLA-DQB1）基因座的等位基因。我们的结果表明，在该地区分型的类似 100 个 SNP 的单一面板足以预测罕见和常见的 HLA 等位基因，在非洲和非非洲人群中预测准确率高达 95%。此外，我们表明，可以通过使用 MHC 内先前基因分型的 SNP 来成功预测 HLA 等位基因，但这些 SNP 并未因其预测 HLA 等位基因的能力而被选择，例如全基因组产品中包含的 SNP。这些结果表明，我们的方法与参考单倍型的扩展数据库相结合，将有助于大规模实验，包括疾病关联研究和疫苗试验，其中有关 HLA 类型的详细信息很有价值。
Genetic variation at classical HLA alleles is a crucial determinant of transplant success and susceptibility to a large number of infectious and autoimmune diseases. However, large-scale studies involving classical type I and type II HLA alleles might be limited by the cost of allele-typing technologies. Although recent studies have shown that some common HLA alleles can be tagged with small numbers of markers, 1,2 SNP-based tagging does not offer a complete solution to predicting HLA alleles. We have developed a new statistical methodology to use SNP variation within the region to predict alleles at key class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1, HLA-DQA1, and HLA-DQB1) loci. Our results indicate that a single panel of similar to 100 SNPs typed across the region is sufficient for predicting both rare and common HLA alleles with up to 95% accuracy in both African and non-African populations. Furthermore, we show that HLA alleles can be successfully predicted by using previously genotyped SNPs that are within the MHC and that had not been chosen for their ability to predict HLA alleles, such as those included on genome-wide products. These results indicate that our methodology, combined with an extended database of reference haplotypes, will facilitate large-scale experiments, including disease-association studies and vaccine trials, in which detailed information about HLA type is valuable.