Cierco-Ayrolles, Christine

Dejean, Sébastien

Druet, Tom

Estivals, Delphine

Gilbert, Hélène

Legarra , Andrés

Mangin, Brigitte

Oumouhou, Naïma

Ytournel, Florence

PubMed

Christine Cierco-Ayrolles

Sébastien Dejean

Andrés Legarra

Hélène Gilbert

Tom Druet

Florence Ytournel

Delphine Estivals

Naïma Oumouhou

Brigitte Mangin

Springer - Publisher Connector

Does probabilistic modelling of linkage disequilibrium evolution improve the accuracy of QTL location in animal pedigree?

International audienceBackground: Since 2001, the use of more and more dense maps has made researchers aware that combining linkage and linkage disequilibrium enhances the feasibility of fine-mapping genes of interest. So, various method types have been derived to include concepts of population genetics in the analyses. One major drawback of many of these methods is their computational cost, which is very significant when many markers are considered. Recent advances in technology, such as SNP genotyping, have made it possible to deal with huge amount of data. Thus the challenge that remains is to find accurate and efficient methods that are not too time consuming. The study reported here specifically focuses on the half-sib family animal design. Our objective was to determine whether modelling of linkage disequilibrium evolution improved the mapping accuracy of a quantitative trait locus of agricultural interest in these populations. We compared two methods of fine-mapping. The first one was an association analysis. In this method, we did not model linkage disequilibrium evolution. Therefore, the modelling of the evolution of linkage disequilibrium was a deterministic process; it was complete at time 0 and remained complete during the following generations. In the second method, the modelling of the evolution of population allele frequencies was derived from a Wright-Fisher model. We simulated a wide range of scenarios adapted to animal populations and compared these two methods for each scenario. Results: Our results indicated that the improvement produced by probabilistic modelling of linkage disequilibrium evolution was not significant. Both methods led to similar results concerning the location accuracy of quantitative trait loci which appeared to be mainly improved by using four flanking markers instead of two. Conclusions: Therefore, in animal half-sib designs, modelling linkage disequilibrium evolution using a Wright-Fisher model does not significantly improve the accuracy of the QTL location when compared to a simpler method assuming complete and constant linkage between the QTL and the marker alleles. Finally, given the high marker density available nowadays, the simpler method should be preferred as it gives accurate results in a reasonable computing time

Legarra, Andres

Mangin, Brigitte, B.

HAL-INSA Toulouse

Background: Since 2001, the use of more and more dense maps has made researchers aware that combining linkage and linkage disequilibrium enhances the feasibility of fine-mapping genes of interest. So, various method types have been derived to include concepts of population genetics in the analyses. One major drawback of many of these methods is their computational cost, which is very significant when many markers are considered. Recent advances in technology, such as SNP genotyping, have made it possible to deal with huge amount of data. Thus the challenge that remains is to find accurate and efficient methods that are not too time consuming. The study reported here specifically focuses on the half-sib family animal design. Our objective was to determine whether modelling of linkage disequilibrium evolution improved the mapping accuracy of a quantitative trait locus of agricultural interest in these populations. We compared two methods of fine-mapping. The first one was an association analysis. In this method, we did not model linkage disequilibrium evolution. Therefore, the modelling of the evolution of linkage disequilibrium was a deterministic process; it was complete at time 0 and remained complete during the following generations. In the second method, the modelling of the evolution of population allele frequencies was derived from a Wright-Fisher model. We simulated a wide range of scenarios adapted to animal populations and compared these two methods for each scenario. Results: Our results indicated that the improvement produced by probabilistic modelling of linkage disequilibrium evolution was not significant. Both methods led to similar results concerning the location accuracy of quantitative trait loci which appeared to be mainly improved by using four flanking markers instead of two. Conclusions: Therefore, in animal half-sib designs, modelling linkage disequilibrium evolution using a Wright-Fisher model does not significantly improve the accuracy of the QTL location when compared to a simpler method assuming complete and constant linkage between the QTL and the marker alleles. Finally, given the high marker density available nowadays, the simpler method should be preferred as it gives accurate results in a reasonable computing time

Dejean, Christophe

Oumouhou, Naima

ProdInra

Scientific Publications of the University of Toulouse II Le Mirail

Cierco-Ayrolles, C.

Dejean, S.

Legarra, A.

Gilbert, H.

Ytournel, F.

Estivals, D.

Mangin, B.

Open Repository and Bibliography - Liège

Mangin, Brigitte,

HAL Descartes

A comparison between methods for linkage disequilibrium fine mapping of quantitative trait loci. Genet Res

A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci.

Coalescent-based association mapping and fine mapping of complex trait loci. Genetics

Comparing linkage disequilibrium-based methods for fine mapping quantitative trait loci. Genetics

Cookson W: Positional cloning of a quantitative trait locus on chromosome

Coppieters W: Molecular dissection of a quantitative trait locus: a phenylalaline-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated witn a major gene effect on milk yield and composition. Genetics

Core Team: R: A Language and Environment for Statistical Computing R Foundation for Statistical Computing,

de la Chapelle: Localization of the EPM1 gene for progressive myoclonus epilepsy on chromosome 21: linkage disequilibrium allows high resolution mapping. Hum Mol Genet

Decomposing multilocus linkage disequilibrium. Genetics

Disequilibrium among several linked genes in finite population I Mean changes in disequilibrium. Theor Popul Biol

Dunner S: Genetic location of heritable traits through association studies: a review. Curr Genomics

E: Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat Genet

Fine mapping of Quantitative Trait Loci affecting female fertility in dairy cattle on BTA03 using a dense single-nucleotide polymorphism map. Genetics

Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci. Genetics

Gametic disequilibrium mapping: potential applications in livestock. Anim Breed Abstr

Le Roy P: Alternative models for QTL detection in livestock I General introduction. Genet Sel Evol

Linkage disequilibrium and QTL fine mapping in a selected population. PhD thesis AgroParisTech;

Linkage disequilibrium and the search for complex disease genes. Genome Res

Linkage disequilibrium in humans : models and data.

Linkage disequilibrium in Huntington’s disease: an improved localisation for the gene.

Linkage disequilibrium interval mapping of quantitative trait loci.

Maximum-likelihood estimation of gene location by linkage disequilibrium.

O: Pedigree analysis by computer simulation. Zoo Biol

On the theory of random mating.

Power and precision of alternate methods for linkage disequilibrium mapping of quantitative trait loci. Genetics

R: A haplotype-based algorithm for multilocus linkage disequilibrium mapping of quantitative trait loci with epistasis. Genetics

Statistical tools for linkage analysis and genetic association studies. Expert Rev Mol Diagn

The decay of linkage disequilibrium under random union of gametes: how to calculate Bennett’s principal components. Theor Popul Biol

https://hal.archives-ouvertes.fr/hal-00663784

Does probabilistic modelling of linkage disequilibrium evolution improve the accuracy of QTL location in animal pedigree?

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

HAL-INSA Toulouse

ProdInra

Scientific Publications of the University of Toulouse II Le Mirail

Open Repository and Bibliography - Liège

HAL Descartes

Springer - Publisher Connector