Abstract
Congenital malformations resulting in late abortions and stillbirths affect the economic wellbeing of producers and the welfare of cattle in breeding programs. An extremely high incidence of stillbirths of “half-sized” calves of normal karyotype and uninflated lungs was diagnosed in the progeny of the Finnish Ayrshire (Bos taurus) bull - YN51. No other visible anatomical abnormalities were apparent in the stillborn calves. We herein describe the positional identification of a 110 kb microdeletion in the maternally imprinted PEG3 domain that results in a loss of paternal MIMT1 expression and causes late term abortion and stillbirth in cattle. Using the BovineSNP50 BeadChip we performed a genome-wide half-sib linkage analysis that identified a 13.3 Mb associated region on BTA18 containing the maternally imprinted PEG3 domain. Within this cluster we found a 110 kb microdeletion that removes a part of the non-protein coding MER1 repeat containing imprinted transcript 1 gene (MIMT1). To confirm the elimination of gene expression in calves inheriting this deletion, we examined the mRNA levels of the three maternally imprinted genes within the PEG3 domain, in brain and cotyledon tissue collected from eight fetuses sired by the proband. None of the fetuses that inherited the microdeletion expressed MIMT1 in either tissue. The mutation, when inherited from the sire, is semi-lethal for his progeny with an observed mortality rate of 85%. The survival of 15% is presumably due to the incomplete silencing of maternally inherited MIMT1 alleles. We designed a PCR-based assay to confirm the existence of the microdeletion in the MIMT1 region that can be used to assist cattle breeders in preventing the stillbirths.
Highlights
Artificial insemination has been used extensively in cattle breeding for over 50 years
We describe a novel mutation in the paternally expressed gene 3 (PEG3) domain that caused stillbirth and late abortion in 42.6% of all offspring in progeny that inherited the mutation from a carrier Finnish Ayrshire (Bos taurus) bull - YN51 whose semen was used to artificially inseminate more than 1,900 females
Field data collected by the Artificial Insemination (AI) Cooperative indicated that 42.6% of the late pregnancies attributed to YN51 ended in stillbirths or abortions
Summary
Artificial insemination has been used extensively in cattle breeding for over 50 years. An unfavorable side-effect of this technique is the risk of widely disseminating mutations that cause hereditary disorders. It is very important from the perspective of population fitness to identify carriers of chromosome [1] or gene [2] mutations. One half of the fetuses can be adversely affected when a male transmits a defective fully penetrant imprinted gene silenced on the maternal allele. The pattern of inheritance of defects within imprinted genes can lead to significant problems for breeding programs. If used in an artificial insemination program such males could produce hundreds or even thousands of progeny before they are detected as transmitting a genetic defect
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