复杂疾病目前正在全球范围流行,极大地影响人类的健康。研究发现,复杂疾病的性状受到多个位点的相互作用影响。目前的全基因组关联分析(Genome-wide association study,GWAS)仅仅解析单个SNP位点对疾病易感性的贡献,单纯依靠这一种策略...复杂疾病目前正在全球范围流行,极大地影响人类的健康。研究发现,复杂疾病的性状受到多个位点的相互作用影响。目前的全基因组关联分析(Genome-wide association study,GWAS)仅仅解析单个SNP位点对疾病易感性的贡献,单纯依靠这一种策略并不能在寻找复杂疾病的病因上得到根本性的突破。基因-基因相互作用可能是复杂疾病致病的主要因素之一。针对这一点,科学家已经提出了一些检验基因相互作用的算法,包括惩罚logistic回归模型、多因子降维(Multifactor dimensional reduction)、集合关联法(Set-association approach)、贝叶斯网络(Bayesian networks)、随机森林法等。文章首先对目前这些方法做了综述,并指出了其中的不足,包括计算复杂度太高、假设驱动、数据会过度拟合、对低维数据不敏感等,进而简述了一种由笔者所在实验室开发的基于GPU的研究基因相互作用的算法,该算法复杂度低,不需要任何假设,没有边际效应,有很好的稳定性,速度快,适用于进行全基因组范围内的基因-基因相互作用计算。展开更多
A qualitative trait is usually controlled by a single gene, but it may be sometimes controlled by two or even more genes. This phenomenon is called gene interaction. Rapidly searching for linked mo- lecular markers vi...A qualitative trait is usually controlled by a single gene, but it may be sometimes controlled by two or even more genes. This phenomenon is called gene interaction. Rapidly searching for linked mo- lecular markers via bulked segregant analysis (BSA) and then constructing regional linkage map with Mapmaker/Exp has become a common approach to mapping single major genes. However, methods and computer programs developed for mapping single major genes cannot be simply applied to interactive genes because the genetic patterns of gene interac- tions are quite different from that of single-gene in- heritance. Up to now, experimental methods for quickly screening molecular markers linked to inter- active genes and statistical methods and corre- sponding computer softwares for simultaneously analyzing the linkage relationships of multiple mo- lecular markers to an interactive gene have not been available. To solve this problem, in this paper, we propose a strategy for mapping interactive genes using BSA and Mapmaker/Exp. We demonstrate that all interactive genes can be mapped by the 'BSA + Mapmaker/Exp' strategy using F2 generation (in a few cases, F3 generation is also needed). As BSA and Mapmaker/Exp have been broadly used in gene mapping studies and are well known by many re- searchers, the strategies proposed in this paper will be useful for practical researches.展开更多
文摘A qualitative trait is usually controlled by a single gene, but it may be sometimes controlled by two or even more genes. This phenomenon is called gene interaction. Rapidly searching for linked mo- lecular markers via bulked segregant analysis (BSA) and then constructing regional linkage map with Mapmaker/Exp has become a common approach to mapping single major genes. However, methods and computer programs developed for mapping single major genes cannot be simply applied to interactive genes because the genetic patterns of gene interac- tions are quite different from that of single-gene in- heritance. Up to now, experimental methods for quickly screening molecular markers linked to inter- active genes and statistical methods and corre- sponding computer softwares for simultaneously analyzing the linkage relationships of multiple mo- lecular markers to an interactive gene have not been available. To solve this problem, in this paper, we propose a strategy for mapping interactive genes using BSA and Mapmaker/Exp. We demonstrate that all interactive genes can be mapped by the 'BSA + Mapmaker/Exp' strategy using F2 generation (in a few cases, F3 generation is also needed). As BSA and Mapmaker/Exp have been broadly used in gene mapping studies and are well known by many re- searchers, the strategies proposed in this paper will be useful for practical researches.
