Gene Mapping, Linkage Analysis, Statistical Methods

Gene mapping has been a major object of Human Genome Project (HGP). Currently, the research methods can be classified into two main classes,that is, genetic linkage analysis and linkage disequilibrium analy-sis.The two methods explore recombination fraction and linkage disequilibrium coefficient correspondly which are used to measure genetical characters ,moreover, statistical methods are used to execute gene mapping.Linkage analysis plays an important role in gene mapping.The foundation: the two gene locuses which locate on the same chromosomal(eg.disease gene and marker gene)happen to cross over and recombine.The farther the distance between two locuses is,the higher the probability happening to cross over is,the lower the probability that the two locuses are inherited to offspring together is, that is,the degree of linkage is not strong.So we can estimate the distance and the degree of linkage by the recombination fraction between the two locuses to locate gene.In this article,we introduce the main methods of linkage analysis,modol-based methods(eg.LOD method),model-free methods(eg.ASP method).Model-based methods firstly need specify the model of inheritance. (l)The number of loci involved. (2) The number of alleles at each locus and their frequen-cies.(3)The penetrances of each genotype. Likelihood ratio test can be applied in this method. Model-free methods do not depend on prior specification of a model of inheritance.for sib pair which has the simplest inheritance structure, it explores Identity-by-descent(IBD) as the association measure and X2 test,likelihood ratio test et.al.The advantages and shortcomings are in sum after every kind of method is described in detail. The part of discussion in this paper highly summarized the historical relationship between Genetics and Mathematics and the future of locating gene.We do further discussion on ASP by using X2 test,mean normal test . further we point and correct the falses of the paper written by Jane M. Olson et.al.1999.