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Genetics, Vol. 178, 2227-2235, April 2008, Copyright © 2008
doi:10.1534/genetics.107.085035

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Fine Mapping of Quantitative Trait Loci Affecting Female Fertility in Dairy Cattle on BTA03 Using a Dense Single-Nucleotide Polymorphism Map

Tom Druet*, Sébastien Fritz{dagger}, Mekki Boussaha{ddagger}, Slim Ben-Jemaa{dagger},{ddagger}, François Guillaume*,§, David Derbala**, Diana Zelenika**, Doris Lechner**, Céline Charon**, Didier Boichard*, Ivo G. Gut**, André Eggen{ddagger} and Mathieu Gautier{ddagger},1

* INRA, UR337 Station de Génétique Quantitative et Appliquée, F-78350 Jouy-en-Josas, France, {dagger} INRA, Union Nationale des Coopératives Agricoles d'Elevage et d'Insémination Animale, F-75595 Paris, France, {ddagger} INRA, UR339 Laboratoire de Génétique Biochimique et Cytogénétique, F-78350 Jouy-en-Josas, France, § Institut de l'Élevage, F-75595 Paris, France and ** CEA/Institut de Génomique—Centre National de Génotypage, F-91057 Evry, France

1 Corresponding author: Laboratoire de Génétique Biochimique et de Cytogénétique, Département de Génétique Animale, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas, France.
E-mail: mathieu.gautier{at}jouy.inra.fr

Fertility quantitative trait loci (QTL) are of high interest in dairy cattle since insemination failure has dramatically increased in some breeds such as Holstein. High-throughput SNP analysis and SNP microarrays give the opportunity to genotype many animals for hundreds SNPs per chromosome. In this study, due to these techniques a dense SNP marker map was used to fine map a QTL underlying nonreturn rate measured 90 days after artificial insemination previously detected with a low-density microsatellite marker map. A granddaughter design with 17 Holstein half-sib families (926 offspring) was genotyped for a set of 437 SNPs mapping to BTA3. Linkage analysis was performed by both regression and variance components analysis. An additional analysis combining both linkage analysis and linkage-disequilibrium information was applied. This method first estimated identity-by-descent probabilities among base haplotypes. These probabilities were then used to group the base haplotypes in different clusters. A QTL explaining 14% of the genetic variance was found with high significance (P < 0.001) at position 19 cM with the linkage analysis and four sires were estimated to be heterozygous (P < 0.05). Addition of linkage-disequilibrium information refined the QTL position to a set of narrow peaks. The use of the haplotypes of heterozygous sires offered the possibility to give confidence in some peaks while others could be discarded. Two peaks with high likelihood-ratio test values in the region of which heterozygous sires shared a common haplotype appeared particularly interesting. Despite the fact that the analysis did not fine map the QTL in a unique narrow region, the method proved to be able to handle efficiently and automatically a large amount of information and to refine the QTL position to a small set of narrow intervals. In addition, the QTL identified was confirmed to have a large effect (explaining 13.8% of the genetic variance) on dairy cow fertility as estimated by nonreturn rate at 90 days.






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