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PLoS One. 2012;7(8):e43085.
A deletion in the bovine FANCI gene compromises
fertility by causing fetal death and brachyspina.
Charlier C, Agerholm JS, Coppieters W, Karlskov-Mortensen P, Li W, de Jong G, Fasquelle C,
Karim L, Cirera S, Cambisano N, Ahariz N, Mullaart E, Georges M, Fredholm M.
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-through-
put SNP genotyping and next-generation sequencing, to identify a 3.3 Kb deletion in the FAN-
CI 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 discre-
pancy 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 signifcantly compromise fertility, and propose a genotype-driven screening strategy to
detect the corresponding deleterious mutation.
Genetic trend for Daughter Fertility in Holstein dairy cattle showing a constant decline over the
last decade.
Mating of a sire carrier of a
defective allele (D) with a car-
rier dam. In this type of cross
one embryo out of four will be
homozygous mutant (DD); if
the mutant embryo dies during
pregnancy, the primary mani-
festation will be a reduction
of fertility. This is typically
the case for the brachyspina
mutation.
Increased pregnancy failure
rate detected as a return into
oestrus at 56, 90 and 270 days
post-insemination in carrier
(D+) x non carrier (++), (++) x
(D+) and (D+) x (D+) over (++) x
(++) matings. All contrasts had
p-value < 10-4. The analyses
were conducted separately for
heifers (blue) and cows (black)
and are perfectly consistent.