Inbreeding depression is the reduction of performance caused by mating of close relatives. In livestock populations, inbreeding depression has been traditionally estimated by regression of phenotypes on pedigree inbreeding coefficients. This estimation can be improved by utilising genomic inbreeding coefficients. Here we estimate inbreeding depression for insect bite hypersensitivity (IBH) prevalence, the most common allergic horse disease worldwide, in Old Kladruber horse. In a deep pedigree with 3214 horses (187 genotyped), we used a generalised linear mixed model with IBH phenotype from 558 horses examined between 1996 and 2009 (1368 records). In addition to the classical pedigree information, we used the single-step approach that enabled joint use of pedigree and genomic information to estimate inbreeding depression overall genome and equine leucocyte antigen (ELA) class II region. Significant inbreeding depression was observed in all models fitting overall inbreeding coefficients (odds ratio between 1.018 and 1.074, P < 0.05) with the exception of Kalinowski's new inbreeding (P = 0.0516). The increase of ELA class II inbreeding was significantly associated with increased prevalence of IBH (odds ratio 1.018; P = 0.027). However, when fitted jointly with the overall inbreeding coefficient, the effect of ELA class II inbreeding was not significant (odds ratio 1.016; P = 0.062). Overall, the higher ELA class II and/or overall inbreeding (pedigree or genomic) was associated with increased prevalence of IBH in Old Kladruber horses. The single-step approach provides an efficient use of all the available pedigree, genomic, and phenotype information for estimation of overall and regional inbreeding effects.

Czech University of Life Sciences Kamycka 129 Prague 16500 Czech Republic

Faculty of Agriculture University of Zagreb Svetošimunska cesta 25 Zagreb 10000 Croatia

Institute of Animal Science Pratelstvi 815 Prague 10400 Czech Republic

South Bohemia University Branisovska 31a Ceske Budejovice 370 05 Czech Republic

The Roslin Institute and Royal School of Veterinary Studies University of Edinburgh Easter Bush Edinburgh Midlothian EH259RG UK

Veterinary Research Institute Hudcova 296 70 Brno 621 00 Czech Republic

See more in PubMed

Andersson L.S., Swinburne J.E., Meadows JRSet al. (2012) The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations. Immunogenetics 64, 201–8. PubMed PMC

Antonios S., Rodríguez‐Ramilo S.T., Aquilar I., Astruc J.M., Legarra A. & Vitezica Z.G. (2021) Genomic and pedigree estimation of inbreeding depression for semen traits in the Basco‐Béarnaise dairy sheep breed. Journal of Dairy Science 104, 3221–30. PubMed

Baker G.A., Mead S.W. & Regan W.M. (1945) Effect of inbreeding on the growth curves of height at withers, weight, and heart girth of Holstein females. Journal of Dairy Science 28, 607–10.

Baumung R., Farkas J., Boichard D., Mészáros G., Sölkner J. & Curik I. (2015) GRAIN: a computer program to calculate ancestral and partial inbreeding coefficients using a gene dropping approach. Journal of Animal Breeding and Genetics 132, 100–8. PubMed

Bittles A.H. & Black M.L. (2010) Consanguinity, human evolution, and complex diseases. Proceedings of the National Academy of Sciences 107, 1779–86. PubMed PMC

Boichard D. (2002) PEDIG: a Fortran package for pedigree analysis suited for large populations. 7th World Congress on Genetics Applied to Livestock Production. 28.

Brinkmeyer‐Langford C.L., Cai J.J., Gill C.A. & Skow L.C. (2013) Microsatellite variation in the equine MHC. Animal Genetics 44, 267–75. PubMed

Burnham K.P. & Anderson D.R. (2002) Model Selection and Multimodel Inference: A Practical Information‐Theoretic Approach, 2nd edn. New York: Springer.

Chang C.C., Chow C.C., Tellier L.C., Vattikuti S., Purcell S.M. & Lee J.J. (2015) Second‐generation PLINK: rising to the challenge of larger and richer datasets. GigaScience 4, 7. PubMed PMC

Christensen O.F. & Lund M.S. (2010) Genomic prediction when some animals are not genotyped. Genetics Selection Evolution 42, 2. PubMed PMC

Citek J., Vostry L., Vostra‐Vydrova H., Brzakova M. & Prantlova V. (2017) Genetic parameters of insect bite hypersensitivity in the Old Grey Kladruber horse. Journal of Animal Science 95, 53–8. PubMed

Crnokrak P. & Roff D.A. (1999) Inbreeding depression in the wild. Heredity 83, 260–70. PubMed

Curik I., Ferenčaković M. & Sölkner J. (2014) Inbreeding and runs of homozygosity: a possible solution to an old problem. Livestock Science 166, 26–34.

Curik I., Ferenčaković M. & Sölkner J. (2017) Genomic dissection of inbreeding depression: a gate to new opportunities. Revista Brasileira de Zootecnia 46, 773–82.

Curik I., Kövér G., Farkas J., Szendrő Z., Romvári R., Sölkner J. & Nagy I. (2020) Inbreeding depression for kit survival at birth in a rabbit population under long‐term selection. Genetics Selection Evolution 52, 39. PubMed PMC

Curik I., Zechner P., Sölkner J., Achmann R., Bodo I., Dovc P., Kavar T., Marti E. & Brem G. (2003) Inbreeding, microsatellite heterozygosity, and morphological traits in lipizzan horses. Journal of Heredity 94, 125–32. PubMed

Doekes H.P., Curik I., Nagy I., Farkas J., Kövér G.Y. & Windig J.J. (2020) Revised calculation of Kalinowski’s ancestral and new inbreeding coefficients. Diversity 12, 155.

Doekes H.P., Veerkamp R.F., Bijma P., de Jong G., Hiemstra S.J. & Windig J.J. (2019) Inbreeding depression due to recent and ancient inbreeding in Dutch Holstein‐Friesian dairy cattle. Genetics Selection Evolution 51, 54. PubMed PMC

Druml T., Neuditschko M., Grilz‐Seger G., Horna M., Ricard A., Mesarič M., Cotman M., Pausch H. & Brem G. (2018) Population networks associated with runs of homozygosity reveal new insights into the breeding history of the haflinger horse. Journal of Heredity 109, 384–92. PubMed

Eriksson S., Grandinson K., Fikse W.F., Lindberg L., Mikko S., Broström H., Frey R., Sundquist M. & Lindgren G. (2008) Genetic analysis of insect bite hypersensitivity (summer eczema) in icelandic horses. Animal 2, 360–5. PubMed

Gómez M.D., Valera M., Molina A., Gutiérrez J.P. & Goyache F. (2009) Assessment of inbreeding depression for body measurements in Spanish Purebred (Andalusian) horses. Livestock Science 122, 149–55.

Grevenhof E.M., Ducro B., Heuven H.C.M. & Bijma P. (2007) Identification of environmental factors affecting the prevalence of insect bite hypersensitivity in Shetland ponies and Friesian horses in the Netherlands. Equine Veterinary Journal 39, 69–73. PubMed

Grilz‐Seger G., Druml T., Neuditschko M., Dobretsberger M., Horna M. & Brem G. (2019) High‐resolution population structure and runs of homozygosity reveal the genetic architecture of complex traits in the Lipizzan horse. BMC Genomics 20, 174. PubMed PMC

Henderson C.R. (1976) A simple method for computing the inverse of a numerator relationship matrix used in prediction of breeding values. Biometrics 32, 69–83.

Hofmanová B., Vostrá‐Vydrová H., Majzlík I. & Vostrý L. (2016) The effect of inbreeding on melanoma and vitiligo occurrence in Old Kladruber grey horses. Acta Agriculturae Slovenica 5, 179–82.

Kalinowski S.T., Hedrick P.W. & Miller P.S. (2000) Inbreeding depression in the Speke’s gazelle captive breeding program. Conservation Biology 14, 1375–84.

Kardos M., Taylor H.R., Ellegren H., Luikart G. & Allendorf F.W. (2016) Genomics advances the study of inbreeding depression in the wild. Evolutionary Applications 9, 1205–18. PubMed PMC

Klemetsdal G. (1998) The effect of inbreeding on racing performance in Norwegian cold‐blooded trotters. Genetics Selection Evolution 30, 351.

Legarra A., Aguilar I. & Colleau J.J. (2020) Short communication: Methods to compute genomic inbreeding for ungenotyped individuals. Journal of Dairy Science 103, 3363–7. PubMed

Legarra A., Aguilar I. & Misztal I. (2009) A relationship matrix including full pedigree and genomic information. Journal of Dairy Science 92, 4656–63. PubMed

Legarra A., Christensen O.F., Vitezica Z.G., Aguilar I. & Misztal I. (2015) Ancestral relationships using metafounders: finite ancestral populations and across population relationships. Genetics 200, 455–68. PubMed PMC

Leroy G. (2014) Inbreeding depression in livestock species: review and meta‐analysis. Animal Genetics 45, 618–28. PubMed

Mahon GAT & Cunningham E.P. (1982) Inbreeding and the inheritance of fertility in the thoroughbred mare. Livestock Production Science 9, 743–54.

Maignel L., Boichard D. & Verrier E. (1996) Genetic variability of French dairy breeds estimated from pedigree information. Interbull Bulletin 14, 49–54.

Marti E., Gerber H. & Lazary S. (1992) On the genetic basis of equine allergic diseases: II. Insect bite dermal hypersensitivity. Equine Veterinary Journal 24, 113–7. PubMed

Mc Parland S., Kearney F. & Berry D.P. (2009) Purging of inbreeding depression within the Irish Holstein‐Friesian population. Genetics Selection Evolution 41, 16. PubMed PMC

McQuillan R., Leutenegger A.L., Abdel‐Rahman R.et al. (2008) Runs of homozygosity in European populations. The American Journal of Human Genetics 83, 359–72. PubMed PMC

Meyermans R., Grossen W., Buys N. & Janssens S. (2020) How to study runs of homozygosity using PLINK? A guide for analysing medium density SNP data in livestock and pet species. BMC Genomics 21, 94. PubMed PMC

Müller‐Unterberg M., Wallmann S. & Distl O. (2017) Effects of inbreeding and other systematic effects on fertility of Black Forest Draught horses in Germany. Acta Veterinaria Scandinavica 59, 70. PubMed PMC

Peeters L.M., Janssens S., Brebels M. & Buys N. (2015) Genetic parameters and estimated breeding values of insect bite hypersensitivity in Belgian Warmblood horses. The Veterinary Journal 206, 420–2. PubMed

Sánchez‐Guerrero M.J., Solé M., Azor P.J., Sölkner J. & Valera M. (2019) Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses. Equine Veterinary Journal 51, 606–11. PubMed

Santure A.W., Stapley J., Ball A.D., Birkhead T.R., Burke T. & Slate J. (2010) On the use of large marker panels to estimate inbreeding and relatedness: empirical and simulation studies of a pedigreed zebra finch population typed at 771 SNPs. Molecular Ecology 19, 1439–51. PubMed

Schurink A., Ducro B.J., Bastiaansen J.W.M., Frankena K. & van Arendonk J.A.M. (2013) Genome‐wide association study of insect bite hypersensitivity in Dutch Shetland pony mares. Animal Genetics 44, 44–52. PubMed

Schurink A., Ducro B.J., Heuven H.C.M. & van Arendonk J.A.M. (2011) Genetic parameters of insect bite hypersensitivity in Dutch Friesian broodmares. Journal of Animal Science 89, 1286–93. PubMed

Schurink A., van Grevenhof E.M., Ducro B.J. & van Arendonk JAM (2009) Heritability and repeatability of insect bite hypersensitivity in Dutch Shetland breeding mares. Journal of Animal Science 87, 484–90. PubMed

Schurink A., Wolc A., Ducro B.J., Frankena K., Garrick D.J., Dekkers J.C. & van Arendonk J.A. (2012) Genome‐wide association study of insect bite hypersensitivity in two horse populations in the Netherlands. Genetics Selection Evolution 44, 31. PubMed PMC

Shrestha M., Eriksson S., Schurink A., Andersson L.S., Sundquist M., Frey R., Broström H., Bergström T., Ducro B. & Lindgren G. (2015) Genome‐wide association study of insect bite hypersensitivity in Swedish‐born Icelandic horses. Journal of Heredity 106, 366–74. PubMed

Šichtař J., Nehasilová A., Šimoník O. & Bubeníčková F. (2017) Effect of two freezing extenders on characteristic of fresh and frozen‐thawed semen in endangered Old Kladruber stallions – a pilot study. Czech Journal of Animal Science 62, 227–33.

Todd E.T., Ho SYW, Thomson P.C., Ang R.A., Velie B.D. & Hamilton N.A. (2018) Founder‐specific inbreeding depression affects racing performance in thoroughbred horses. Scientific Reports 8, 6167. PubMed PMC

Unkel M., Simon D., Mayer M. & Sommer H. (1987) Zur genetischen Fundierung des Sommerekzems beim Islandpferd. Journal of Animal Breeding and Genetics 104, 217–30.

Valera M., Molina A., Gutiérrez J.P., Gómez J. & Goyache F. (2005) Pedigree analysis in the Andalusian horse: population structure, genetic variability and influence of the Carthusian strain. Livestock Production Science 95, 57–66.

van der Rijt R., Van der Boom R., De Jongema Y. & Sloet van Oldruitenborgh‐Oosterbaan M.M. (2008) Culicoides species attracted to horses with and without insect hypersensitivity. The Veterinary Journal 178, 91–7. PubMed

van Eldik P., van der Waaij E.H., Ducro B., Kooper A.W., Stout T.A.E. & Colenbrander B. (2006) Possible negative effects of inbreeding on semen quality in Shetland pony stallions. Theriogenology 65, 1159–70. PubMed

VanRaden P. (2008) Efficient methods to compute genomic predictions. Journal of Dairy Science 91, 4414–23. PubMed

Velie B.D., Shrestha M., Franҫois L.et al. (2016) Using an inbred horse breed in a high density genome‐wide scan for genetic risk factors of insect bite hypersensitivity (IBH). PLoS One 11, e0152966. PubMed PMC

Vicente A.A., Carolino N. & Gama L.T. (2012) Genetic diversity in the Lusitano horse breed assessed by pedigree analysis. Livestock Science 148, 16–25.

Vostrá‐Vydrová H., Vostrý L., Hofmanová B., Krupa E. & Zavadilová L. (2016) Pedigree analysis of the endangered Old Kladruber horse population. Livestock Science 185, 17–23.

Vostrý L., Čapková Z., Přibyl J. & Mach K. (2011) Analysis of czech cold‐blooded horses: genetic parameters, breeding value and the influence of inbreeding depression on linear description of conformation and type characters. Czech Journal of Animal Science 56, 217–30.