Advanced SearchSearch Tips
Evaluation of a New Fine-mapping Method Exploiting Linkage Disequilibrium: a Case Study Analysing a QTL with Major Effect on Milk Composition on Bovine Chromosome 14
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
Evaluation of a New Fine-mapping Method Exploiting Linkage Disequilibrium: a Case Study Analysing a QTL with Major Effect on Milk Composition on Bovine Chromosome 14
Kim, JongJoo; Georges, Michel;
  PDF(new window)
A novel fine-mapping method exploiting linkage disequilibrium (LD) was applied to better refine the quantitative trait loci (QTL) positions for milk production traits on bovine chromosome 14 in the pedigree comprising 22 paternal half-sib families of a Black-and-White Holstein-Friesian grand-daughter design in the Netherlands for a total of 1,034 sons. The chromosome map was constructed with the 31 genetic markers spanning 90 Kosambi cM with the average inter-marker distance of 3.5 cM. The linkage analyses, in which the effects of sire QTL alleles were assumed random and the random factor of the QTL allelic effects was incorporated into the Animal Model, found the QTL for milk, fat, and protein yield and fat and protein % with the Lod scores of 10.9, 2.3, 6.0, 25.4 and 3.2, respectively. The joint analyses including LD information by use of multi-marker haplotypes highly increased the evidence of the QTL (Lod scores were 25.1, 20.9, 11.0, 85.7 and 17.4 for the corresponding traits, respectively). The joint analyses including DGAT markers in the defined haplotypes again increased the QTL evidence and the most likely QTL positions for the five traits coincided with the position of the DGAT gene, supporting the hypothesis of the direct causal involvement of the DGAT gene. This study strongly indicates that the exploitation of LD information will allow additional gains of power and precision in finding and localising QTL of interest in livestock species, on the condition of high marker density around the QTL region.
Linkage Mapping;Linkage Disequilibrium Mapping;QTL;Milk Production Traits;Dairy Cattle;
 Cited by
Genetic Evaluation and Calculating Daughter Yield Deviation of Bulls in Iranian Holstein Cattle for Milk and Fat Yields,Sheikhloo, M.;Shodja, J.;Pirany, N.;Alijani, S.;Sayadnejad, M.B.;

Asian-Australasian Journal of Animal Sciences, 2009. vol.22. 5, pp.611-617 crossref(new window)
Detection of QTL on Bovine X Chromosome by Exploiting Linkage Disequilibrium,Kim, Jong-Joo;

Asian-Australasian Journal of Animal Sciences, 2008. vol.21. 5, pp.617-623 crossref(new window)
Coppieters, W., J. Riquet, J. Arranz, P. Berzi, N. Cambisano, B. Grisart, L. Karim, F. Marcq, L. Moreau, C. Nezer, P. Simon, P. Vanmanshoven, D. Wagenaar and M. Georges. 1998. A QTL with major effect on milk yield and composition maps to bovine chromosome 14. Mamm. Genome 9:540-544. crossref(new window)

Daly, M. J., J. D. Rioux, S. F. Schaffner, T. J. Hudson and E. S. Lander. 2001. High-resolution haplotype structure in the human genome. Nature Genet. 29:229-232. crossref(new window)

Farnir, F., W. Coppieters, J. Arranz, P. Berzi, N. Cambisano, B. Grisart, L. Karim, F. Marcq, L. Moreau, M. Mni, C. Nezer, P. Simon, P. Vanmanshoven, D. Wagenaar and M. Georges. 2000. Extensive genome-wide linkage disequilibrium in cattle. Genome Res. 10:220-227. crossref(new window)

Farnir, F., B. Grisart, W. Coppieters, J. Riquet, P. Berzi, N. Cambisano, L. Karim, M. Mni, S. Moisio, P. Simon, D. Wagenaar, J. Vilkki and M. Georges. 2002. Simultaneous mining of linkage and linkage disequilibrium to fine-map QTL in outbred half-sib pedigrees: revisiting the location of a QTL with major effect on milk production on bovine chromosome 14. Genetics 161:275-287.

Grisart, B., W. Coppieters, F. Farnir, L. Karim, C. Ford, N. Cambisano, M. Mni, S. Reid, R. Spelman, M. Georges and R. Snell. 2002. Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT gene with major effect on milk yield and composition. Genome Res. 12:222-231. crossref(new window)

Heyen, D. W., J. L. Weller, M. Ron, M. Band, J. E. Beever, E. Feldmesser, Y. Da, G. R. Wiggans, P. M. VanRaden and H. A. Lewin. 1999. A genome scan for QTL influencing milk production and health traits in dairy cattle. Physiol. Genomics 1:165-175.

Hudson, R. R. 1985. The sampling distribution of linkage disequilibrium under an infinite alleles model without selection. Genetics 109:611-631.

Jeffreys, A. J., L. Kauppi and R. Neumann. 2001. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nature Genet. 29:217-222. crossref(new window)

Johnson, D. L. and R. Thompson. 1995. Restricted maximum likelihood estimation of variance components for univariate Animal Models using sparse matrix techniques and average information. J. Dairy. Sci. 78:449-456.

Kim, J. J. and Y. I. Park. 2001. Current status of quantitative trait locus mapping in livestock species. Asian-Aust. J. Anim. Sci. 14(4):587-596.

Kim, J. J., F. Farnir, W. Coppieters and M. Georges. 2002. A novel joint linkage and linkage disequilibrium mapping enhanced QTL detection power and mapping precision in outbred halfsib pedigrees: I. methodology and simulation. (In preparation).

Looft, C., N. Reinsch, C. Karall-Albrecht, S. Paul, M. Brink, H. Thomsen, G. Brockmann, C. Kuhn, M. Schwerin and E. Kalm. 2001. A mammary gland EST showing linkage disequilibrium to a milk production QTL on bovine Chromosome 14. Mamm. Genome 12:646-650. crossref(new window)

Mount, D. W. 2001. Bioinformatics: Sequence and Genome analysis. Cold Spring Harbor Laboratory Press, New York, New York.

Meuwissen, T. H. E. and M. E. Goddard. 2000. Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci. Genetics 155:421-430.

Meuwissen, T. H. E. and M. E. Goddard. 2001. Prediction of identity by descent probabilities from marker-haplotypes. Genet. Sel. Evol. 33:605-634. crossref(new window)

Reich, D. E. and E. S. Lander. 2001. On the allelic spectrum of human disease. Trends In Genetics 17:502-510. crossref(new window)

Riquet, J., W. Coppieters, N. Cambisano, J. Arranz, P. Berzi, S. K. Davis, B. Grisart, F. Farnir, L. Karim, M. Mni, P. Simon, J. F. Taylor, P. Vanmanshoven, D. Wagenaar, J. E. Womack and M. Georges. 1999. Fine-mapping of quantitative trait loci by identity by descent in outbred populations: application to milk production in dairy cattle. Proc. Natl. Acad. Sci. USA 96:9252-9257. crossref(new window)

Terwilliger, J. D. 1995. A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. Am. J. Hum. Genet. 56:777-787.

Van Raden, P. M. and G. R. Wiggens. 1991. Derivation calculating and use of National Animal Model Information. J. Dairy Sci. 74:2737-2746.

Weller, J. I., Y. Kashi and M. Soller. 1990. Power of daughter and granddaughter designs for genetic mapping of quantitative traits in dairy cattle using genetic markers. J. Dairy Sci. 73:2525-2537.