A Multilocus Model for Constructing a Linkage Disequilibrium Map in Human Populations

Abstract

The extent and pattern of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a statistical algorithm for constructing a joint linkage-linkage disequilibrium map by simultaneously estimating the recombination fraction and linkage disequilibrium between different molecular markers in a natural human population. This algorithm was devised with a set of random unrelated families, each including a father, a mother and a varying number of offspring, sampled from a population at Hardy-Weinberg equilibrium. A two-level hierarchical mixture model framework was built, in which the likelihood of genotype data for the parents was formulated in terms of linkage disequilibrium at an upper level, whereas the likelihood of genetic transmission from the parents to offspring formulated in terms of the recombination fraction at a lower level. The EM algorithm was implemented to obtain a closed system of maximum likelihood estimates of marker co-segregation and co-transmission. The model allows a number of testable hypotheses about population genetic parameters, opening a broad gateway to understand the genetic structure and dynamics of an outcrossing population under natural selection. The new strategy will provide a platform for studying the genetic control of inherited diseases in which genetic material is accurately copied before being passed onto the offspring from a parent.

Inferring the evolutionary history of outcrossing populations through computing a multiallelic linkage–linkage disequilibrium map

“…Li & Wu () were among the first who renovated the joint linkage‐LD analysis for studying the genetic variation of human populations. More recently, Sun et al .…”

“…The model should be renovated to allow the test of sex‐specific diversification in each or a combination of these parameters, finding its better implication for evolutionary studies. This extension was found not to be difficult technically, but its practical use depends on a large sample size (Li & Wu ). Secondly, our model is based on a two‐point analysis, which should be extended to include a three‐point analysis.…”

A unifying experimental design for dissecting tree genomes

“…These two pieces of information regarding sex-and generation-dependent differences provide an important view of recent historical trends in genetic diversity and architecture by evolutionary forces [17]. Li and Wu [28] provide a procedure for testing these hypotheses, advancing the application of the OP design to evolutionary genetic studies.…”

Summarizing and Quantifying Multilocus Linkage Disequilibrium Patterns with Multi-Order Markov Chain Models

“…Lou et al (2003Lou et al ( , 2005 and Liu et al (2004) provided a general approach and formula for the parameter estimation. Li and Wu (2008) proposed a family-structured study design for LD mapping, which is useful to identify certain diplotypes given the information of the parent's generation. Gusev et al (2008) developed the computer program ENT, which can be efficiently applied for phasing the gigantic genotype data from the Genome-Wide Association Study.…”