Affiliation:
1. Department of Pathobiology and Population Sciences The Royal Veterinary College, University of London Hatfield UK
2. Department of Comparative Biomedical Sciences The Royal Veterinary College, University of London London UK
3. Department of Clinical Science and Services The Royal Veterinary College, University of London London UK
4. Department of Veterinary Integrative Biosciences Texas A&M University College Station Texas USA
Abstract
AbstractBackgroundExcessive inbreeding increases the probability of uncovering homozygous recessive genotypes and has been associated with an increased risk of retained placenta and lower semen quality. No genomic analysis has investigated the association between inbreeding levels and pregnancy loss.ObjectivesTo compare genetic inbreeding coefficients (F) of naturally occurring Thoroughbred Early Pregnancy Loss (EPLs), Mid and Late term Pregnancy Loss (MLPL) and Controls. The F value was hypothesised to be higher in cases of pregnancy loss (EPLs and MLPLs) than Controls.Study designObservational case–control study.MethodsAllantochorion and fetal DNA from EPL (n = 37, gestation age 14–65 days), MLPL (n = 94, gestational age 70 days–24 h post parturition) and Controls (n = 58) were genotyped on the Axiom Equine 670K SNP Genotyping Array. Inbreeding coefficients using Runs of Homozygosity (FROH) were calculated using PLINK software. ROHs were split into size categories to investigate the recency of inbreeding.ResultsMLPLs had significantly higher median number of ROH (188 interquartile range [IQR], 180.8–197.3), length of ROH (3.10, IQR 2.93–3.33), and total number of ROH (590.8, IQR 537.3–632.3), and FROH (0.26, IQR 0.24–0.28) when compared with the Controls and the EPLs (p < 0.05). There was no significant difference in any of the inbreeding indices between the EPLs and Controls. The MLPLs had a significantly higher proportion of long (>10 Mb) ROH (2.5%, IQR 1.6–3.6) than the Controls (1.7%, IQR 0.6–2.5), p = 0.001. No unique ROHs were found in the EPL or MLPL populations.Main limitationsSNP‐array data does not allow analysis of every base in the sequence.ConclusionsThis first study of the effect of genomic inbreeding levels on pregnancy loss showed that inbreeding is a contributor to MLPL, but not EPL in the UK Thoroughbred population. Mating choices remain critical, because inbreeding may predispose to MLPL by increasing the risk of homozygosity for specific lethal allele(s).
Funder
Horserace Betting Levy Board
Royal Veterinary College