Mapping asthma-associated variants in admixed populations.
Mapping asthma-associated variants in admixed populations.
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DOI：
10.3389/fgene.2015.00292
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发表时间：
2015
影响因子：
3.7
通讯作者：
Mersha TB
中科院分区：
文献类型：
--
作者：
Mersha TB
当两个或两个以上先前隔离的种群杂交时，就会出现混合种群。使用混合物作图（AM）在混合人群中定位哮喘易感性基因座涉及筛选混合血统个体的基因组，以寻找与具有较低哮喘风险的亲本人群相比具有来自具有较高哮喘风险的亲本人群的等位基因频率更高的染色体区域。AM利用混合血统人群中产生的混合物来鉴定遗传血统与哮喘之间存在关联的基因组区域（与标记物的基因型与哮喘之间的关联相反）。AM背后的理论是，受影响个体的染色体片段包含来自高风险亲本群体的等位基因的比例显著高于平均水平，因此更可能含有疾病相关基因座。评估AM作为基因定位方法的适用性的标准包括：（1）混合群体形成的祖先群体中疾病差异的普遍性;（2）亲本群体之间致病等位基因的可测量差异;（3）染色体上未连锁位点之间的连锁不平衡（LD）降低，相邻位点之间的LD较强;（4）在亲本群体之间具有显著等位基因频率差异的一组标记有助于混合群体（单核苷酸多态性（SNP）是选择的标记，因为它们丰富、稳定、基因分型相对便宜，并且关于染色体区段的LD结构提供信息）;和（5）了解节段染色体混合物的程度及其与环境因素的相互作用。虽然全基因组关联研究极大地促进了我们对哮喘遗传成分的理解，但世界各地人群中大量且不断增加的混合程度为进一步绘制致病基因的努力带来了许多挑战。这篇综述总结了混合人群和AM的历史背景，并考虑了当前使用AM绘制哮喘基因的机会。此外，我们还概述了AM在生物医学研究中的潜在局限性和未来方向，包括哮喘和哮喘相关疾病的联合混合物和关联映射。
Admixed populations arise when two or more previously isolated populations interbreed. Mapping asthma susceptibility loci in an admixed population using admixture mapping (AM) involves screening the genome of individuals of mixed ancestry for chromosomal regions that have a higher frequency of alleles from a parental population with higher asthma risk as compared with parental population with lower asthma risk. AM takes advantage of the admixture created in populations of mixed ancestry to identify genomic regions where an association exists between genetic ancestry and asthma (in contrast to between the genotype of the marker and asthma). The theory behind AM is that chromosomal segments of affected individuals contain a significantly higher-than-average proportion of alleles from the high-risk parental population and thus are more likely to harbor disease–associated loci. Criteria to evaluate the applicability of AM as a gene mapping approach include: (1) the prevalence of the disease differences in ancestral populations from which the admixed population was formed; (2) a measurable difference in disease-causing alleles between the parental populations; (3) reduced linkage disequilibrium (LD) between unlinked loci across chromosomes and strong LD between neighboring loci; (4) a set of markers with noticeable allele-frequency differences between parental populations that contributes to the admixed population (single nucleotide polymorphisms (SNPs) are the markers of choice because they are abundant, stable, relatively cheap to genotype, and informative with regard to the LD structure of chromosomal segments); and (5) there is an understanding of the extent of segmental chromosomal admixtures and their interactions with environmental factors. Although genome-wide association studies have contributed greatly to our understanding of the genetic components of asthma, the large and increasing degree of admixture in populations across the world create many challenges for further efforts to map disease-causing genes. This review, summarizes the historical context of admixed populations and AM, and considers current opportunities to use AM to map asthma genes. In addition, we provide an overview of the potential limitations and future directions of AM in biomedical research, including joint admixture and association mapping for asthma and asthma-related disorders.
影响因子：
2.9
作者：
Johnson RC;Nelson GW;Zagury JF;Winkler CA
通讯作者：
Winkler CA