Abstract
A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.
Full Text
The Full Text of this article is available as a PDF (103.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aasland M., Våge D. I., Lien S., Klungland H. Resolution of conflicting assignments for the bovine casein kinase II alpha (CSNK2A2) gene. Anim Genet. 2000 Apr;31(2):131–134. doi: 10.1046/j.1365-2052.2000.00615.x. [DOI] [PubMed] [Google Scholar]
- Farnir F., Coppieters W., Arranz J. J., Berzi P., Cambisano N., Grisart B., Karim L., Marcq F., Moreau L., Mni M. Extensive genome-wide linkage disequilibrium in cattle. Genome Res. 2000 Feb;10(2):220–227. doi: 10.1101/gr.10.2.220. [DOI] [PubMed] [Google Scholar]
- Hoeschele I., Uimari P., Grignola F. E., Zhang Q., Gage K. M. Advances in statistical methods to map quantitative trait loci in outbred populations. Genetics. 1997 Nov;147(3):1445–1457. doi: 10.1093/genetics/147.3.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karlsen A., Ruane J., Klemetsdal G., Heringstad B. Twinning rate in Norwegian cattle: frequency, (co)variance components, and genetic trends. J Anim Sci. 2000 Jan;78(1):15–20. doi: 10.2527/2000.78115x. [DOI] [PubMed] [Google Scholar]
- Kruglyak L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet. 1999 Jun;22(2):139–144. doi: 10.1038/9642. [DOI] [PubMed] [Google Scholar]
- Lien S., Karlsen A., Klemetsdal G., Våge D. I., Olsaker I., Klungland H., Aasland M., Heringstad B., Ruane J., Gomez-Raya L. A primary screen of the bovine genome for quantitative trait loci affecting twinning rate. Mamm Genome. 2000 Oct;11(10):877–882. doi: 10.1007/s003350010180. [DOI] [PubMed] [Google Scholar]
- Meuwissen T. H., Goddard M. E. Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci. Genetics. 2000 May;155(1):421–430. doi: 10.1093/genetics/155.1.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meuwissen T. H., Goddard M. E. Prediction of identity by descent probabilities from marker-haplotypes. Genet Sel Evol. 2001 Nov-Dec;33(6):605–634. doi: 10.1186/1297-9686-33-6-605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Terwilliger J. D., Weiss K. M. Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr Opin Biotechnol. 1998 Dec;9(6):578–594. doi: 10.1016/s0958-1669(98)80135-3. [DOI] [PubMed] [Google Scholar]
- Van Vleck L. D., Gregory K. E., Echternkamp S. E. Ovulation rate and twinning rate in cattle: heritabilities and genetic correlation. J Anim Sci. 1991 Aug;69(8):3213–3219. doi: 10.2527/1991.6983213x. [DOI] [PubMed] [Google Scholar]