title: A two-stage approximation for analysis of mixture genetic models in large pedigrees.
abstract: Information from cosegregation of marker and QTL alleles, in addition to linkage disequilibrium (LD), can improve genomic selection. Variance components linear models have been proposed for this purpose, but accommodating dominance and epistasis is not straightforward with them. A full-Bayesian analysis of a mixture genetic model is favorable in this respect, but is computationally infeasible for whole-genome analyses. Thus, we propose an approximate two-step approach that neglects information from trait phenotypes in inferring ordered genotypes and segregation indicators of markers. Quantitative trait loci (QTL) fine-mapping scenarios, using high-density markers and pedigrees of five generations without genotyped females, were simulated to test this strategy against an exact full-Bayesian approach. The latter performed better in estimating QTL genotypes, but precision of QTL location and accuracy of genomic breeding values (GEBVs) did not differ for the two methods at realistically low LD. If, however, LD was higher, the exact approach resulted in a slightly higher accuracy of GEBVs. In conclusion, the two-step approach makes mixture genetic models computationally feasible for high-density markers and large pedigrees. Furthermore, markers need to be sampled only once and results can be used for the analysis of all traits. Further research is needed to evaluate the two-step approach for complex pedigrees and to analyze alternative strategies for modeling LD between QTL and markers.
authors.affiliation: Institute of Animal Breeding and Husbandry, Christian-Albrechts University of Kiel, 24098 Kiel, Germany. dhabier@gmail.com
authors.forename: D
authors.initials: D
authors.lastname: Habier
authors.forename: L R
authors.initials: LR
authors.lastname: Totir
authors.forename: R L
authors.initials: RL
authors.lastname: Fernando
mesh_terms: D000483:Alleles; D000818:Animals; D001499:Bayes Theorem; D001947:Breeding; D002874:Chromosome Mapping / Q000379:methods; D005260:Female; D016678:Genome; D005838:Genotype; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci
references.citation: Genetics. 2000 May;155(1):421-30
references.pmid: 10790414
references.citation: Genetics. 1999 Apr;151(4):1605-19
references.pmid: 10101181
references.citation: Nat Genet. 2008 Sep;40(9):1068-75
references.pmid: 19165921
references.citation: Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363-7
references.pmid: 3470801
references.citation: Genetics. 1998 Mar;148(3):1373-88
references.pmid: 9539450
references.citation: Am J Hum Genet. 1997 Sep;61(3):748-60
references.pmid: 9326339
references.citation: J Dairy Sci. 2009 Jan;92(1):16-24
references.pmid: 19109259
references.citation: Genetics. 2003 Apr;163(4):1497-510
references.pmid: 12702692
references.citation: Genet Sel Evol. 2009 Sep 29;41:43
references.pmid: 19788745
references.citation: Genet Sel Evol. 2010 Feb 19;42:5
references.pmid: 20170500
references.citation: Genetics. 2004 Jun;167(2):967-75
references.pmid: 15238545
references.citation: Genetics. 2006 Mar;172(3):1955-65
references.pmid: 16322505
references.citation: Genetics. 2008 Jan;178(1):553-61
references.pmid: 18202394
references.citation: Genet Res. 2000 Oct;76(2):187-98
references.pmid: 11132412
references.citation: Hum Hered. 1971;21(6):523-42
references.pmid: 5149961
references.citation: Genet Sel Evol. 2001 May-Jun;33(3):209-29
references.pmid: 11403745
references.citation: Genet Res. 2005 Aug;86(1):77-87
references.pmid: 16181525
references.citation: Genetics. 2007 Dec;177(4):2389-97
references.pmid: 18073436
references.citation: Genet Res. 2002 Apr;79(2):185-98
references.pmid: 12073556
references.citation: J Dairy Sci. 2009 Feb;92(2):433-43
references.pmid: 19164653
references.citation: Bioinformatics. 2002;18 Suppl 1:S189-98
references.pmid: 12169547
references.citation: Genet Sel Evol. 2001 Jul-Aug;33(4):337-67
references.pmid: 11559482
references.citation: Genetics. 2008 Jul;179(3):1503-12
references.pmid: 18622038
references.citation: Genetics. 2005 Jul;170(3):1333-44
references.pmid: 15911579
references.citation: Am J Hum Genet. 2000 Jul;67(1):155-69
references.pmid: 10835299
references.citation: Genetics. 2001 Apr;157(4):1819-29
references.pmid: 11290733
references.citation: Am J Hum Genet. 1989 Apr;44(4):543-51
references.pmid: 2929597
references.citation: Genet Sel Evol. 2007 Jan-Feb;39(1):27-38
references.pmid: 17212946
references.citation: Genetics. 2003 Oct;165(2):867-83
references.pmid: 14573494
references.citation: Biometrics. 1993 Mar;49(1):163-75
references.pmid: 8513101
references.citation: Genet Sel Evol. 2003 Nov-Dec;35(6):585-604
references.pmid: 14604509
references.citation: Am J Hum Genet. 2002 Feb;70(2):496-508
references.pmid: 11791215
references.citation: Genet Sel Evol. 2001 Sep-Oct;33(5):453-71
references.pmid: 11712969
references.citation: Genetics. 2005 Apr;169(4):2305-18
references.pmid: 15520261