Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability - Genetics Selection Evolution Access content directly
Journal Articles Genetics Selection Evolution Year : 2024

Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability

Maxime Ben Braiek
Carole Moreno-Romieux
  • Function : Author
Céline André
  • Function : Author
Jean-Michel Astruc
  • Function : Author
Philippe Bardou
  • Function : Author
Arnaud Bordes
  • Function : Author
Frédéric Debat
  • Function : Author
Francis Fidelle
  • Function : Author
Itsasne Granado-Tajada
Chris Hozé
  • Function : Author
Florence Plisson-Petit
  • Function : Author
François Rivemale
  • Function : Author
Julien Sarry
  • Function : Author
Némuel Tadi
  • Function : Author
Florent Woloszyn
  • Function : Author
Stéphane Fabre
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Abstract

AbstractBackgroundRecessive deleterious variants are known to segregate in livestock populations, as in humans, and some may be lethal in the homozygous state.ResultsWe used phased 50 k single nucleotide polymorphism (SNP) genotypes and pedigree data to scan the genome of 6845 Manech Tête Rousse dairy sheep to search for deficiency in homozygous haplotypes (DHH). Five Manech Tête Rousse deficient homozygous haplotypes (MTRDHH1 to 5) were identified, with a homozygous deficiency ranging from 84 to 100%. These haplotypes are located on Ovis aries chromosome (OAR)1 (MTRDHH2 and 3), OAR10 (MTRDHH4), OAR13 (MTRDHH5), and OAR20 (MTRDHH1), and have carrier frequencies ranging from 7.8 to 16.6%. When comparing at-risk matings between DHH carriers to safe matings between non-carriers, two DHH (MTRDHH1 and 2) were linked with decreased insemination success and/or increased stillbirth incidence. We investigated the MTRDHH1 haplotype, which substantially increased stillbirth rate, and identified a single nucleotide variant (SNV) inducing a premature stop codon (p.Gln409*) in the methylmalonyl-CoA mutase (MMUT) gene by using a whole-genome sequencing approach. We generated homozygous lambs for the MMUT mutation by at-risk mating between heterozygous carriers, and most of them died within the first 24 h after birth without any obvious clinical symptoms. Reverse transcriptase-qPCR and western blotting on post-mortem liver and kidney biological samples showed a decreased expression of MMUT mRNA in the liver and absence of a full-length MMUT protein in the mutant homozygous lambs.ConclusionsWe identified five homozygous deficient haplotypes that are likely to harbor five independent deleterious recessive variants in sheep. One of these was detected in the MMUT gene, which is associated with lamb lethality in the homozygous state. A specific management of these haplotypes/variants in the MTR dairy sheep selection program would help enhance the overall fertility and lamb survival.
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Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution
Origin Publication funded by an institution

Dates and versions

hal-04487621 , version 1 (04-03-2024)

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Maxime Ben Braiek, Carole Moreno-Romieux, Céline André, Jean-Michel Astruc, Philippe Bardou, et al.. Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability. Genetics Selection Evolution, 2024, 56 (1), pp.16. ⟨10.1186/s12711-024-00886-7⟩. ⟨hal-04487621⟩
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