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Abstract
BackgroundThe goal of linkage analysis is to determine the chromosomal location of the gene(s) for a trait of interest such as a common disease. Three-locus linkage analysis is an important case of multi-locus problems. Solutions can be found analytically for the case of triple backcross mating. However, in the present study of linkage analysis and gene mapping some natural inequality restrictions on parameters have not been considered sufficiently, when the maximum likelihood estimates (MLEs) of the two-locus recombination fractions are calculated.ResultsIn this paper, we present a study of estimating the two-locus recombination fractions for the phase-unknown triple backcross with two offspring in each family in the framework of some natural and necessary parameter restrictions. A restricted expectation-maximization (EM) algorithm, called REM is developed. We also consider some extensions in which the proposed REM can be taken as a unified method.ConclusionOur simulation work suggests that the REM performs well in the estimation of recombination fractions and outperforms current method. We apply the proposed method to a published data set of mouse backcross families.
Highlights
The goal of linkage analysis is to determine the chromosomal location of the gene(s) for a trait of interest such as a common disease
As Ott [3] pointed out, under regular conditions, each of these phases occurs with probability 1/4. When it is not the case, we let the prior probability be hi (i = 1, 2, 3, 4) in a later section, and give corresponding feasible approach. This estimation problem of two-locus recombination fractions in three-locus linkage analysis belongs to the constrained parameter problems which are important and appear in many areas
We develop a restricted EM algorithm, called REM, which gives estimating results
Summary
The goal of linkage analysis is to determine the chromosomal location of the gene(s) for a trait of interest such as a common disease. Three-locus linkage analysis is an important case of multi-locus problems. In the present study of linkage analysis and gene mapping some natural inequality restrictions on parameters have not been considered sufficiently, when the maximum likelihood estimates (MLEs) of the two-locus recombination fractions are calculated. Genetic linkage refers to the ordering of genetic loci on a chromosome and to estimating genetic distances among them, where these distances are determined on the basis of a statistical phenomenon. A critical first step in finding gene loci that contribute to a genetic trait is to demonstrate linkage with a gene of known location (marker). Estimating the recombination fractions is important in linkage analysis
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