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Mapping Variants in the Equine Genome Incompatible with Life

Principal Investigator: Mandi de Mestre

Baker Institute for Animal Health
Sponsor: Harry M. Zweig Memorial Fund for Equine Research
Title: Mapping Variants in the Equine Genome Incompatible with Life
Project Amount: $93,750
Project Period: January 2026 to December 2026

DESCRIPTION (provided by applicant):

Early pregnancy loss (EPL) remains one of the greatest challenges in equine reproductive health as it is very common and the underlying cause often not identified. We recently showed aneuploidy is the most common cause but the role of other genetic variants is poorly understood. Single nucleotide polymorphisms are associated with fetal lethality in humans. These variants can arise from de novo mutations, often paternal germline derived, or biallelically inherited mutations that can lead to recessive lethal phenotypes. In preliminary studies, using Genome Wide Association Studies (GWAS) and deep sequencing, we have identified loci and rare variants associated with euploid and/or aneuploid EPL. We hypothesize that inherited recessive lethal SNPs in key developmental genes that disrupt gene function may result in euploid EPL, whilst multiple risk alleles will have an additive effect to increase the risk of aneuploidy. De novo mutations will be rare contributors. We will perform two case-control GWAS studies to identify SNPs associated with euploid (Aim 1) and aneuploid (Aim 2) EPL DeepVariant applied to sequences will identify rare deleterious mutations.