Detection of Lethal Mutations in Sheep: Research for Homozygous Chromosome Segments with High Density Molecular Information (54 000 SNPs)

The intermittent appearance of lethal mutations can cause production problems in sheep. They are often due to the intensive use of some rams, which leads to a reduction of genetic variability and the emergence of deleterious mutations. The aim of this study is to detect genomic regions (~1 Mb) harboring recessive deleterious mutations within breeds by identifying frequent haplotypes of 15 SNPs (0.5%) showing a deficit in homozygotes. The Illumina ovine 54k SNP beadchip, (available in genomic selection databases of two dairy French sheep breeds, 7428 Lacaune and 2102 Manech Tête Rousse) was used. Eight different haplotypes with a significant deficit were identified: three in Lacaune and five in Manech, including one with no homozygous animals on OAR20. The frequency of haplotypes with a significant deficit ranged from 5 to 20%. These deficits in homozygotes can be due to lethal mutations but also to a gene selected directly or indirectly for a trait of interest in the genotyped population. For example, the haplotype detected on OAR3 in Lacaune breed was found highly linked to the unfavorable mutation of a gene affecting mastitis resistance, which is a trait selected in Lacaune breed. On the other hand, the haplotype detected on OAR20 in Manech breed is located close to a positional candidate gene involved in male fertility problem in mice and Humans. The identification of causal mutations under the deficits in homozygotes is now on going. The counter-selection of these unfavorable mutations will improve fertility in French sheep selection schemes.