Does inbreeding contribute to pregnancy loss in Thoroughbred horses?
abortion
fetus
homozygosity
horse
mare
miscarriage
Journal
Equine veterinary journal
ISSN: 2042-3306
Titre abrégé: Equine Vet J
Pays: United States
ID NLM: 0173320
Informations de publication
Date de publication:
14 Jan 2024
14 Jan 2024
Historique:
received:
13
03
2023
accepted:
29
12
2023
medline:
15
1
2024
pubmed:
15
1
2024
entrez:
15
1
2024
Statut:
aheadofprint
Résumé
Excessive 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. To 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. Observational case-control study. Allantochorion 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. MLPLs 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 F SNP-array data does not allow analysis of every base in the sequence. This 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).
Sections du résumé
BACKGROUND
BACKGROUND
Excessive 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.
OBJECTIVES
OBJECTIVE
To 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 DESIGN
METHODS
Observational case-control study.
METHODS
METHODS
Allantochorion 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.
RESULTS
RESULTS
MLPLs 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 F
MAIN LIMITATIONS
CONCLUSIONS
SNP-array data does not allow analysis of every base in the sequence.
CONCLUSIONS
CONCLUSIONS
This 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).
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Horserace Betting Levy Board
Organisme : Thoroughbred Breeders Association
Organisme : Royal Veterinary College
Organisme : The Alborada Trust
Informations de copyright
© 2024 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Références
McGivney BA, Han H, Corduff LR, Katz LM, Tozaki T, MacHugh DE, et al. Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred horse population. Sci Rep. 2020;10:1-12.
Gurgul A, Szmatoła T, Topolski P, Jasielczuk I, Żukowski K, Bugno-Poniewierska M. The use of runs of homozygosity for estimation of recent inbreeding in Holstein cattle. J Appl Genet. 2016;57:527-530.
Alemu SW, Kadri NK, Harland C, Faux P, Charlier C, Caballero A, et al. An evaluation of inbreeding measures using a whole-genome sequenced cattle pedigree. Heredity. 2021;126:410-423.
Howrigan DP, Simonson MA, Keller MC. Detecting autozygosity through runs of homozygosity: a comparison of three autozygosity detection algorithms. BMC Genomics. 2011;12:1-15.
Keller MC, Visscher PM, Goddard ME. Quantification of inbreeding due to distant ancestors and its detection using dense single nucleotide polymorphism data. Genetics. 2011;189:237-249.
Sevinga M, Vrijenhoek T, Hesselink J, Barkema H, Groen A. Effect of inbreeding on the incidence of retained placenta in Friesian horses. J Anim Sci. 2004;82:982-986.
Aurich C, Achmann R, Aurich JE. Semen parameters and level of microsatellite heterozygosity in Noriker draught horse stallions. Theriogenology. 2003;60:371-378.
Van Eldik P, Van Der Waaij E, Ducro B, Kooper A, Stout T, Colenbrander B. Possible negative effects of inbreeding on semen quality in Shetland pony stallions. Theriogenology. 2006;65:1159-1170.
Dini P, Bartels T, Revah I, Claes AN, Stout TA, Daels P. A retrospective study on semen quality parameters from four different Dutch horse breeds with different levels of inbreeding. Theriogenology. 2020;157:18-23.
Ducro B. Relevance of test information in horse breeding. Wageningen, The Netherlands: Wageningen University and Research; 2011.
Mahon G, Cunningham E. Inbreeding and the inheritance of fertility in the thoroughbred mare. Livest Product Sci. 1982;9:743-754.
Müller-Unterberg M, Wallmann S, Distl O. Effects of inbreeding and other systematic effects on fertility of Black Forest Draught horses in Germany. Acta Vet Scand. 2017;59:1-6.
Cothran E, MacCluer J, Weitkamp L, Pfennig D, Boyce A. Inbreeding and reproductive performance in Standardbred horses. J Hered. 1984;75:220-224.
Sairanen J, Nivola K, Katila T, Virtala A-M, Ojala M. Effects of inbreeding and other genetic components on equine fertility. Animal. 2009;3:1662-1672.
Valera M, Blesa F, Dos Santos R, Molina A. Genetic study of gestation length in Andalusian and Arabian mares. Anim Reprod Sci. 2006;95:75-96.
Gonçalves RW, da Costa M, Rocha J, da Costa M, Silva E, Ribeiro A. Inbreeding effect on reproductive traits in a herd of Mangalarga Marchador Brazilian horses. Rev Bras Saúde Prod Anim. 2011;12:641-649.
Bene S, Benedek Z, Szabo F, Polgár P. Some effects on gestation length of traditional horse breeds in Hungary. J Cent Eur Agric. 2014;15:1-10.
Christmann A, Sieme H, Martinsson G, Distl O. Genetic and environmental factors influencing gestation length and parturition conception interval in Hanoverian Warmblood. Livest Sci. 2017;199:63-68.
Ewert M, Lüders I, Böröcz J, Uphaus H, Distl O, Sieme H. Determinants of gestation length in Thoroughbred mares on German stud farms. Anim Reprod Sci. 2018;191:22-33.
Todd ET, Hamilton NA, Velie BD, Thomson PC. The effects of inbreeding on covering success, gestation length and foal sex ratio in Australian thoroughbred horses. BMC Genet. 2020;21:1-9.
Rodrigues JA, Gonçalves AR, Antunes L, Bettencourt EV, Gama LT. Genetic and environmental factors influencing gestation length in Lusitano horses. J Equine Vet. 2020;84:102850.
Klemetsdal G, Johnson M. Effect of inbreeding on fertility in Norwegian trotter. Livest Product Sci. 1989;21:263-272.
Rose B, Firth M, Morris B, Roach J, Wathes D, Verheyen K, et al. Descriptive study of current therapeutic practices, clinical reproductive findings and incidence of pregnancy loss in intensively managed thoroughbred mares. Anim Reprod Sci. 2018;188:74-84.
Roach JM, Foote AK, Smith KC, Verheyen KL, de Mestre AM. Incidence and causes of pregnancy loss after Day 70 of gestation in Thoroughbreds. Equine Vet J. 2021;53:996-1003.
Shilton CA, Kahler A, Roach JM, Raudsepp T, de Mestre AM. Lethal variants of equine pregnancy: is it the placenta or foetus leading the conceptus in the wrong direction? Reprod Fertil Dev. 2023;35:51-69.
Hamstead L, Chang Y-M, Crowhurst J, Wise Z, McGladdary A, Ricketts S, et al. Retrospective study of early pregnancy loss in Thoroughbred mares. Equine Vet J. 2012;44:2-18.
Macleay CM, Carrick J, Shearer P, Begg A, Stewart M, Heller J, et al. A scoping review of the global distribution of causes and syndromes associated with mid-to late-term pregnancy loss in horses between 1960 and 2020. Vet Sci. 2022;9:186.
Rose BV, Cabrera-Sharp V, Firth MJ, Barrelet FE, Bate S, Cameron IJ, et al. A method for isolating and culturing placental cells from failed early equine pregnancies. Placenta. 2016;38:107-111.
Shilton CA, Kahler A, Davis BW, Crabtree JR, Crowhurst J, McGladdery AJ, et al. Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse. Sci Rep. 2020;10:13314.
Robbin MG, Wagner B, Noronha LE, Antczak DF, de Mestre AM. Subpopulations of equine blood lymphocytes expressing regulatory T cell markers. Vet Immunol Immunopathol. 2011;140:90-101.
Meyermans R, Gorssen W, Buys N, Janssens S. How to study runs of homozygosity using PLINK? A guide for analyzing medium density SNP data in livestock and pet species. BMC Genomics. 2020;21:1-14.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559-575.
Grilz-Seger G, Mesarič M, Cotman M, Neuditschko M, Druml T, Brem G. Runs of homozygosity and population history of three horse breeds with small population size. J Equine Vet. 2018;71:27-34.
Druml T, Neuditschko M, Grilz-Seger G, Horna M, Ricard A, Mesarič M, et al. Population networks associated with runs of homozygosity reveal new insights into the breeding history of the Haflinger horse. J Hered. 2018;109:384-392.
McQuillan R, Leutenegger A-L, Abdel-Rahman R, Franklin CS, Pericic M, Barac-Lauc L, et al. Runs of homozygosity in European populations. Am J Hum Genet. 2008;83:359-372.
Fawcett JA, Sato F, Sakamoto T, Iwasaki WM, Tozaki T, Innan H. Genome-wide SNP analysis of Japanese Thoroughbred racehorses. PloS One. 2019;14:e0218407.
Drögemüller M, Jagannathan V, Welle MM, Graubner C, Straub R, Gerber V, et al. Congenital hepatic fibrosis in the Franches-Montagnes horse is associated with the polycystic kidney and hepatic disease 1 (PKHD1) gene. PloS One. 2014;9:e110125.
Ducro BJ, Schurink A, Bastiaansen JW, Boegheim IJ, van Steenbeek FG, Vos-Loohuis M, et al. A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC Genomics. 2015;16:1-9.
Aurich C, Müller-Herbst S, Reineking W, Müller E, Wohlsein P, Gunreben B, et al. Characterization of abortion, stillbirth and non-viable foals homozygous for the Warmblood Fragile Foal Syndrome. Anim Reprod Sci. 2019;211:106202.
Grillos A, Roach J, de Mestre A, Foote A, Kinglsey N, Mienaltowski M, et al. First reported case of fragile foal syndrome type 1 in the Thoroughbred caused by PLOD1 c. 2032G>A. Equine Vet J. 2021;54(6):1086-1093.
Orlando L, Librado P. Origin and evolution of deleterious mutations in horses. Genes. 2019;10:649.
Weatherbys Weatherbys Factbook 2020. Wellingborough, UK: Weatherbys GSB Ltd; 2020.
Authority BH. Fact Book 2014. London, UK: British Horseracing Authority; 2014. p. 49.