title: A deletion in the bovine FANCI gene compromises fertility by causing fetal death and brachyspina.
abstract: Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades. We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping and next-generation sequencing, to identify a 3.3 Kb deletion in the FANCI gene causing the brachyspina syndrome (BS), a rare recessive genetic defect in Holstein dairy cattle. We determine that despite the very low incidence of BS (<1/100,000), carrier frequency is as high as 7.4% in the Holstein breed. We demonstrate that this apparent discrepancy is likely due to the fact that a large proportion of homozygous mutant calves die during pregnancy. We postulate that several other embryonic lethals may segregate in livestock and significantly compromise fertility, and propose a genotype-driven screening strategy to detect the corresponding deleterious mutations.
authors.affiliation: Unit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of Liège (B34), Liège, Belgium. carole.charlier@ulg.ac.be
authors.forename: Carole
authors.initials: C
authors.lastname: Charlier
authors.forename: Jorgen Steen
authors.initials: JS
authors.lastname: Agerholm
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
authors.forename: Peter
authors.initials: P
authors.lastname: Karlskov-Mortensen
authors.forename: Wanbo
authors.initials: W
authors.lastname: Li
authors.forename: Gerben
authors.initials: G
authors.lastname: de Jong
authors.forename: Corinne
authors.initials: C
authors.lastname: Fasquelle
authors.forename: Latifa
authors.initials: L
authors.lastname: Karim
authors.forename: Susanna
authors.initials: S
authors.lastname: Cirera
authors.forename: Nadine
authors.initials: N
authors.lastname: Cambisano
authors.forename: Naima
authors.initials: N
authors.lastname: Ahariz
authors.forename: Erik
authors.initials: E
authors.lastname: Mullaart
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.forename: Merete
authors.initials: M
authors.lastname: Fredholm
mesh_terms: D000822:Animal Husbandry / Q000379:methods; D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping / Q000379:methods; D003433:Crosses, Genetic; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics*; D005260:Female; D005298:Fertility; D005313:Fetal Death; D017353:Gene Deletion; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011270:Pregnancy, Animal; D017384:Sequence Deletion
chemical_list: D051856:Fanconi Anemia Complementation Group Proteins