Estimation of Recombination Rate and Maternal Linkage Disequilibrium in Half-Sibs.

Alexander Hampel,Luis Gomez-Raya,Michael Doschoris,Friedrich Teuscher,Dörte Wittenburg

doi:10.3389/fgene.2018.00186

Abstract

A livestock population can be characterized by different population genetic parameters, such as linkage disequilibrium and recombination rate between pairs of genetic markers. The population structure, which may be caused by family stratification, has an influence on the estimates of these parameters. An expectation maximization algorithm has been proposed for estimating these parameters in half-sibs without phasing the progeny. It, however, overlooks the fact that the underlying likelihood function may have two maxima. The magnitudes of the maxima depend on the maternal allele frequencies at the investigated marker pair. Which maximum the algorithm converges to depends on the chosen start values. We present a stepwise procedure in which the relationship between the two modes is exploited. The expectation maximization algorithm for the parameter estimation is applied twice using different start values, followed by a decision process to assess the most likely estimate. This approach was validated using simulated genotypes of half-sibs. It was also applied to a dairy cattle dataset consisting of multiple half-sib families and 39,780 marker genotypes, leading to estimates for 12,759,713 intrachromosomal marker pairs. Furthermore, the proper order of markers was verified by studying the mean of estimated recombination rates in a window adjacent to the investigated locus as well as in a window at its most distant chromosome end. Putatively misplaced markers or marker clusters were detected by comparing the results with the revised bovine genome assembly UMD 3.1.1. In total, 40 markers were identified as candidates of misplacement. This outcome may help improving the physical order of markers which is also required for refining the bovine genetic map.

Highlights

Population genetic parameters, such as linkage disequilibrium (LD) and recombination rate, are relevant parameters for characterizing a livestock population
The first simulation study showed that EMT0 and EMDP performed well for the small-θ setting in terms of bias and MSE of θand Ddam
If N = 1,000, bias and MSE reduced for all approaches and EMDP performed best overall in terms of MSE (Tables S1, S2)

Summary

Introduction

Population genetic parameters, such as linkage disequilibrium (LD) and recombination rate, are relevant parameters for characterizing a livestock population. Methods for genomic selection (e.g., Meuwissen et al, 2001) implicitly exploit the LD between quantitative trait loci (QTL) and genetic markers for estimating breeding values or genetic effects captured by the markers in a population. The accuracy of estimated effects depends on the extent of LD (e.g., Hayes et al, 2009), which is affected by several factors (e.g., Ardlie et al, 2002). Estimation of Recombination Rate linkage between chromosomal segments. A recombination event creates new combinations of alleles in the generation. Population structure influences the extent of LD differing between populations and breeds (De Roos et al, 2008) and between families within a breed (Dekkers, 2004)

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Discussion

Conclusion