Abstract
BackgroundHomozygous recessive deleterious mutations can cause embryo/fetal or neonatal lethality, or genetic defects that affect female fertility and animal welfare. In livestock populations under selection, the frequency of such lethal mutations may increase due to inbreeding, genetic drift, and/or the positive pleiotropic effects of heterozygous carriers on selected traits.ResultsBy scanning the genome of 19,102 Lacaune sheep using 50 k single nucleotide polymorphism (SNP) phased genotypes and pedigree data, we identified 11 Lacaune deficient homozygous haplotypes (LDHH1 to LDHH11) showing a highly significant deficit of homozygous animals ranging from 79 to 100%. These haplotypes located on chromosomes 3, 4, 13, 17 and 18, spanned regions from 1.2 to 3.0 Mb long with a frequency of heterozygous carriers between 3.7 and 12.1%. When we compared at-risk matings (between carrier rams and daughters of carrier rams) and safe matings, seven of the 11 haplotypes were associated with a significant alteration of two fertility traits, a reduced success of artificial insemination (LDHH1, 2, 8 and 9), and/or an increased stillbirth rate (LDHH3, 6, 8, 9, and 10). The 11 haplotypes were also tested for a putative selective advantage of heterozygous carrier rams based on their daughter yield deviation for six dairy traits (milk, fat and protein yields, fat and protein contents and lactation somatic cell score). LDHH1, 3, 4, 5, 7, 9 and 11 were associated with positive effects on at least one selected dairy trait, in particular milk yield. For each haplotype, the most probable candidate genes were identified based on their roles in lethality of mouse knock-out models and in mammalian genetic disorders.ConclusionsBased on a reverse genetic strategy, we identified at least 11 haplotypes with homozygous deficiency segregating in French Lacaune dairy sheep. This strategy represents a first tool to limit at-risk matings in the Lacaune dairy selection scheme. We assume that most of the identified LDHH are in strong linkage disequilibrium with a recessive lethal mutation that affects embryonic or juvenile survival in sheep but is yet to be identified.
Highlights
Homozygous recessive deleterious mutations can cause embryo/fetal or neonatal lethality, or genetic defects that affect female fertility and animal welfare
The frequency of recessive lethal alleles could increase in a population if they are associated with heterozygous advantages due to positive pleiotropic effects on selected production traits such as milk production in dairy cattle [6, 7], in the homozygous state they are responsible for embryonic losses
We studied a first set of two fertility traits, i.e. artificial insemination success (AIS) and stillbirth rate (SBR)
Summary
Homozygous recessive deleterious mutations can cause embryo/fetal or neonatal lethality, or genetic defects that affect female fertility and animal welfare. Even if genetic diversity and inbreeding parameters are managed, selection programs provide a fairly favorable context for the emergence of homozygous individuals with genetic defects that increase in frequency with inbreeding and/or overuse of certain sires and can jeopardize fertility in the whole population [5] This has been observed in cattle where about 1% of the embryos die due to their homozygosity at one of the 10 identified lethal embryonic mutations [1]. The frequency of recessive lethal alleles could increase in a population if they are associated with heterozygous advantages due to positive pleiotropic effects on selected production traits such as milk production in dairy cattle [6, 7], in the homozygous state they are responsible for embryonic losses Identification of these causal mutations has become a major issue with the emergence of genetic defects with obvious consequences on animal welfare and have major economic implications.
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