Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2 - PubMed (original) (raw)

. 2013 Jun 7;8(6):e65550.

doi: 10.1371/journal.pone.0065550. Print 2013.

Aurelien Capitan, Anis Djari, Sabrina C Rodriguez, Anne Barbat, Aurélia Baur, Cécile Grohs, Bernard Weiss, Mekki Boussaha, Diane Esquerré, Christophe Klopp, Dominique Rocha, Didier Boichard

Affiliations

Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2

Sébastien Fritz et al. PLoS One. 2013.

Abstract

The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10(-4)) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle.

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Conflict of interest statement

Competing Interests: Genotypes originated from three projects funded by ANR and ApisGene, and from genomic selection activity generated by seven French cattle breeding companies (Creavia, Amelis, Genes Diffusion, Midatest, Umotest, Jura Betail, Interselection Normande). The whole genome sequence data originated from the CartoSeq project funded by ANR and ApisGene. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

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