Estimation of runs of homozygosity reveals moderate autozygosity in North European sheep breeds

Document Type : Research Article (Regular Paper)

Authors

1 Payam Noor University, Mashad

2 Shahid Bahonar University of Kerman

3 Department of Animal Science, Shahid Bahonar University of Kerman, Kerman, Iran. TEL: +98 34 31322691

Abstract

Runs of homozygosity (ROH) stretches are continuous homozygous fragments of the genome, which are more suitable for calculating genomic inbreeding, identifying footprints involved in economic traits and understanding population history in livestock species. In this study, using a dataset of Ovine SNP50 BeadChip genotypes, the distribution of ROH across the nine different sheep populations (Soay n= 110, Australian Poll Dorset n=108, Australian Suffolk, n=109, Finn sheep, n= 99 , Scottish Texel, n= 80 , Scottish Blackface, n= 56 , Galway, n= 49 , Border Leicester, n= 48 , German Texel, n=46) from Europe were investigated. ROHs were detected by used PLINK v1.09 with the minimal number of SNPs in ROH was set to 40; the maximal gap between the adjacent SNPs was set1 to Mb; the minimum SNP density per ROH was set to 1/100 kb and no heterozygote allowed less than 16 Mb. The detected ROHs were specified based on length to four categories: 1–4 Mb, 4–8 Mb, 8–16 Mb and above 16 Mb. A total of 22,204 ROHs were identified, in which ~ 92 – 98 % of them were less than 16 Mb in length, which covered 4.6% to 12.9% of the entire genome. The inbreeding coefficient based on ROH (FROH) varied among populations (ranging from 0.05 to 0.14). The highest inbreeding rate was found in Border Leicester and Soay breeds. In addition, we detected 90 possible ROH Islands that were overlapped with candidate genes associated with different economic traits such as; body weight, meat production, fat deposition, horn-less, and coat color in sheep. Our results suggest that although genetic selection for meat and wool traits in these breeds have been extensively carried out for the last decades, the autozygotic proportion of their genome is still considerably low, and it could lead an acceptable response to selection in breeding schemes.

Keywords

Main Subjects


References

Albrechtsen, A., Nielsen, F.C., Nielsen, R., 2010. Ascertainment biases in SNP chips affect measures of population divergence. Molcular Biology Evolution 27, 2534-2547.
Al-Mamun, H.A., Clark, S.A., Kwan, P., Gondro, C., 2015. Genome-wide linkage disequilibrium and genetic diversity in five populations of Australian domestic sheep. Genetic Selection Evolution 47, 90-104.
Al-Mamun, H.A., Clark, S.A., Kwan. P., Gondro, C., 2019. Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight. Genetic Selection Evolution 47, 66-77.
Asadollahpour Nanaei, H., Dehghani Qanatqestani, M., Esmailizadeh, A., 2020. Whole-genome resequencing reveals selection signatures associated with milk production traits in African Kenana dairy zebu cattle. Genomics 112, 880-885.
Asadollahpour Nanaei, H., Esmailizadeh, A., Ayatollahi Mehrgardi, A., Han, J., Wu, D.D., Li, Y., Zhang, Y.P., 2020. Comparative population genomic analysis uncovers novel genomic footprints and genes associated with small body size in Chinese pony. BMC Genomics 21, 496-506.
Barazandeh, A., Mohammadabadi, M.R., Ghaderi-Zefrehei, M., Rafeied, F, Imumorin, I.G., 2019. Whole genome comparative analysis of CpG islands in camelid and other mammalian genomes. Mammalian Biology 98, 73-79.
Barbato, M., Orozco-terWengel, P., Tapio, M., Bruford, M.W., 2015. SNeP: a tool to estimate trends in recent effective population size trajectories using genome-wide SNP data. Frontiers Genetic 6, 109-115.
Beynon, S.E., Slavov, G.T., Farre, M., 2015. Population structure and history of the Welsh sheep breeds determined by whole genome genotyping. BMC Genetics 16, 65-79.
Bjelland, D.W., Weigel, K.A., Vukasinovic, N., Nkrumah, J.D., 2013. Evaluation of inbreeding depression in Holstein cattle using whole-genome SNP markers and alternative measures of genomic inbreeding. Journal of Dairy Science 96, 4697-4706.
Bosse, M., Megens, H.J., Madsen, O., Paudel, Y., Frantz, L.A., Schook, L.B., 2012. Regions of homozygosity in the porcine genome: consequence of demography and the recombination landscape. PLoS Genetic 8, e1003100.
Burren, A., Neuditschko, M., Signer-Hasler, H., Frischknecht, M., Reber, I., Menzi, F., Drogem uller, C., Flury, C., 2016. Genetic diversity analyses reveal first insights into breed-specific selection signatures within Swiss goat breeds. Animal Genetic 47, 727-739.
Carothers, A.D., Rudan, I., Kolcic, I., Polasek, O., Hayward, C., Wright, A.F., Campbell, H., Teague, P., Hastie, N. D., Weber, J.L., 2006. Estimating human inbreeding coefficients: comparison of genealogical and marker heterozygosity approaches. Annal Human Genetics 70, 666-676.
Chessa, B., Pereira, F., Arnaud, F., Amorim, A., Goyache, F., Mainland, I. Kao, R. R., Pemberton, J. M., Beraldi, D., Stear, M. J., Alberti, A., Pittau, M., Iannuzzi, L., Banabazi, M. H., Kazwala, R. R., Zhang, Y. P., Arranz, J. J., Ali, B. A., Wang, Z., Uzun, M., Palmarini, M., 2009. Revealing the history of sheep domestication using retrovirus integrations. Science 24, 532-536.
Clark, A.G., Hubisz, M.J., Bustamante, C.D., Williamson, S.H., and Nielsen, R., 2005. Ascertainment bias in studies of human genome-wide polymorphism. Genome Research 15, 1496-1502.
Clop, A., Marcq, F., Takeda, H., Pirottin, D., Tordoir, X., Bibé, B., Bouix, J. Caiment, F., Elsen, J.M., Eychenne, F., Larzul, C., Laville, E., Meish, F., Milenkovic, D., Tobin, J., Charlier, C., Georges, M., 2006. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nature Genetic 38, 813-818.Daetwyler, H.D., Swan, A.A., van der Werf, J.H., Hayes, B.J., 2012. Accuracy of pedigree and genomic predictions of carcass and novel meat quality traits in multi-breed sheep data assessed by cross-validation. Genetic Selection Evolution 44, 33-44.
Fang, Q., Forrest, R.H., Zhou, H., Frampton, C.M., Hickford, J.G.H., 2013. Variation in exon 10 of the ovine calpain 3 gene (CAPN3) and its association with meat yield in New Zealand Romney sheep. Meat Science 94, 388-390.
Ferenčaković, M., Hamzic, E., Gredler, B., Curik, I., Solkner, J., 2011. Runs of homozygosity reveal genome-wide autozygosity in the Austrian fleckvieh cattle. Agriculture Conspectus Scientificus 76, 325-328.
Ferencaković, M., Hamzić, E., Gredler, B., Solberg, T.R., Klemetsdal, G., Curik, I., Sölkner, J., 2013a. Estimates of autozygosity derived from runs of homozygosity: empirical evidence from selected cattle populations. Journal of Animal Breeding and Genetics 130, 286-293
Ferencakovic, M., Solkner, J. and Curik, I., 2013b. Estimating autozygosity from high-throughput information: effects of SNP density and genotyping errors. Genetic Selection Evolution 45, 42-51.
Fontanesi, L., Beretti, F., Riggio, V., Dall’Olio, S., Calascibetta, D., Russo, V., Portolano, B., 2010. Sequence characterization of the melanocortin 1 receptor (MC1R) gene in sheep with different coat colours and identification of the putative e allele at the ovine extension locus. Small Ruminant Resourse 91, 200-207.
Fontanesi, L., Beretti. F., Riggio, V., Dall’Olio, S., González, E.G., Finocchiaro, R., Davoli, R., Russo, V., Portolano, B., 2009. Missense and nonsense mutations in melanocortin 1 receptor (MC1R) gene of different goat breeds: association with red and black coat colour phenotypes but with unexpected evidences. BMC Genetics10 :47.
Food and Agriculture Organization. Domestic Animal Diversity Information System (DAD-IS); available at: www.fao.org/dadis. [Accessed 14/02/2019 ].
Gibson, J., Morton, N.E., Collins, A., 2006. Extended tracts of homozygosity in outbred human populations. Human Molecular Genetics 15, 789-795.
Guangul, S.A. 2014. Design of community based breeding programs for two indigenous goat breeds of Ethiopia. Ph.D. Thesis, University of Natural Resources and Life Sciences, Vienna.
Gurgul, A., Szmatoła, T., Topolski, P., Jasielczuk, I., Żukowski, K., Bugno-Poniewierska, M., 2016. The use of runs of homozygosity for estimation of recent inbreeding in Holstein cattle. Journal of Applied Genetics 57, 527-530.
Han, J., Kraft, P., Nan, H., Guo, Q., Chen, C., Qureshi, A., Hankinson, S.E., Huet, F.B., Duffy, D.L., Zhao, Z.Z., Martin, N.G., Montgomery, G.W., Hayward, N. K., Thomas, G., Hoover, R.N., Chanock, S., Hunter, D.J., 2008. A genome‑wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genetics 4 e1000074.
Herrero-Medrano, J.M., Megens, H.J., Groenen, M.A.M., Ramis, G., Bosse, M., Perez-Enciso, M., Crooijmans, R.P.M.A., 2013. Conservation genomic analysis of domestic and wild pig populations from the Iberian Peninsula. BMC Genetics 14, 106-118.
Howrigan, D.P., Simonson, M.A., Keller, M.C., 2011. Detecting autozygosity through runs of homozygosity: a comparison of three autozygosity detection algorithms. BMC Genomics 12, 460-473.
Johnston, S.E., Beraldi, D., McRae, A.F., Pemberton, J.M., Slate, J., 2010. Horn type and horn length genes map to the same chromosomal region in Soay sheep. Heredity 104, 196-205.
Kijas, J.W., Lenstra, J.A., Hayes, B., Boitard, S., Porto Neto, L.R., San Cristobal, M., Servin, B., McCulloch, R., Whan, V., Gietzen, K., Paiva, S., Barendse, W., Ciani, E., Raadsma, H., McEwan, J., Dalrymple, B., 2012. Genome-wide analysis of the world’s sheep breeds reveals high levels of historic mixture and strong recent selection. PLoS Biology 10:e1001258.
Kim, E.S., Cole, J.B., Huson, H., Wiggans, G.R., Van Tassell, C.P., Crooker, B.A., Liu, G., Da, Y., Sonstegard, T.S., 2013. Effect of artificial selection on runs of homozygosity in U.S. Holstein cattle. PLoS ONE 8: e80813.
Kim, E.S., Elbeltagy, A.R., Aboul-Naga, A.M., Rischkowsky, B., Sayre, B., Mwacharo, J.M., Rothschild, M.F., 2016. Multiple genomic signatures of selection in goats and sheep indigenous to a hot arid environment. Heredity 10, 255-264.
Kirin, M., McQuillan, R., Franklin, C.S., Campbell, H., McKeigue, P.M., Wilson, J.F., 2010. Genomic runs of homozygosity record population history and consanguinity. PLoS ONE 5:e13996.
Lawson Handley, L., Byrne, K., Santucci, F., Townsend, S., Taylor, M., Bruford, M.W., Hewitt, G.M., 2007. Genetic structure of European sheep breeds. Heredity 99, 620-631
Lencz, T., Lambert, C., DeRosse, P., Burdick, K.E., Morgan, T.V., Kane, J.M., Kucherlapati, R. and Malhotra, A.K., 2007. Runs of homozygosity reveal highly penetrant recessive loci in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America 104, 19942-19947.
Marras, G., Gaspa, G., Sorbolini, S., Dimauro, C., Ajmone-Marsam, P., Valentini, A., Williams, J.L., Macciotta, N.P.P., 2014. Analysis of runs of homozygosity and their relationship with inbreeding in five cattle breeds farmed in Italy. Animal Genetics 46, 110-121.
Mastrangelo, S., Bahbahani, H., Moioli, B., Ahbara, A., Al Abri, M., Almathen, F., da Silva, A., Belabdi, I., Portolano, B., Mwacharo, J.M., Hanotte, O., Pilla, F., Ciani, E.,2019. Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia. PLoS ONE 14:e0209632.
Mastrangelo, S., Ciani, E., Sardina, M.T., Sottile, G., Pilla, F., Portolano, B., 2018. Runs of homozygosity reveal genome-wide autozygosity in Italian sheep breeds. Animal Genetics 49, 71-81.
Mastrangelo, S., Tolone, M., Di Gerlando, R., Fontanesi, L., Sardina, M.T., Portolano, B., 2016. Genomic inbreeding estimation in small populations: evaluation of runs of homozygosity in three local dairy cattle breeds. Animal 10, 746-754.
Mastrangelo, S., Tolone, M., Sardina, M.T., Sottile, G., Sutera, A. M., Di Gerlando, R., Portolano, B., 2017. Genome-wide scan for runs of homozygosity identifies potential candidate genes associated with local adaptation in Valle del Belice sheep. Genetics Selection Evolution 49, 84-94.
McHugo, G.P., Browett, S., Randhawa, I., Howard, D.J., Mullen, M.P., Richardson, I.W., Park, S., Magee, D.A., Scraggs, E., Dover, M. J., Correia, C. N., Hanrahan, J. P., MacHugh, D. E., 2019. A population genomics analysis of the native Irish Galway sheep breeds. Frontiers in Genetics 10, 927-940.
McQuillan, R., Leutenegger, A.L., Abdel-Rahman, R., Franklin, C.S., Pericic, M., Barac-Lauc, L., 2008. Runs of Homozygosity in European populations. American Journal of Human Genetics 83, 359-372.
Meira, A., Montenegro, H., Coutinho, L., Mourão, G., Azevedo, H., Muniz, E., Pinto, L., 2019 Single nucleotide polymorphisms in the growth hormone and IGF type-1 (IGF1) genes associated with carcass traits in Santa Ines sheep. Animal 13, 460-468.
Moradian, H., Esmailizadeh, A.K., Asadi, M., Mohammadabadi, M.R., 2019. Whole genome detection of recent selection signatures in Sarabi cattle: a unique Iranian taurine breed. Genes & Genomics 96, 1-13.
Muchadeyi, F.C., Malesa, M.T., Somam,P., Dzomba, E.F., 2015. Runs of homozygosity in Swakara pelt producing sheep: implications on sub-vital performance. Proceedings of the Association for the Advancement of Animal Breeding and Genetics 21, 310-313.
Pemberton, T., Absher, D., Feldman, M., Myers, R., Rosenberg, N., Li, J., 2012. Genomic patterns of homozygosity in worldwide human populations. American Journal of Human Genetics 91, 275-292.
Peter, C., Bruford, M., Perez, T., Dalamitra, S., Hewitt, G., Erhardt, G., 2007. Genetic diversity and subdivision of 57 European and Middle-Eastern sheep breeds. Animal Genetics 38,37-44.
Prieur, V., Clarke, S.M., Brito, L.F., McEwan, J.C., Lee, M.A., Brauning, R., Dodds, K.G., Auvray, B., 2017. Estimation of linkage disequilibrium and effective population size in New Zealand sheep using three different methods to create genetic maps. BMC Genetics 18, 68-79.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D. Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J., Sham, P.C., 2007. PLINK: a tool set for whole genome association and population-based linkage analyses. American Journal of Human Genetics 81, 559-575.
Purfield, D.C., Berry, D.P., McParland, S., Bradley, D.G., 2012. Runs of homozygosity and population history in cattle. BMC Genetics 13, 70-83.
Purfield, D.C., McParland, S., Wall, E., Berry, D.P., 2017. The distribution of runs of homozygosity and selection signatures in six commercial meat sheep breeds. 12: e0176780.
Qanbari, S., Gianola, D., Hayes, B., Schenkel, F., Miller, S., Moore, S., Thaller, G., Simianer, H., 2011. Application of site and haplotype-frequency based approaches for detecting selection signatures in cattle. BMC Genomics 12, 318-329.
Qanbari, S., Pimentel, E.C.G., Tetens, J., Thaller, G., Lichtner, P., Sharifi, A.R., Simianer, H., 2010. The pattern of linkage disequilibrium in German Holstein cattle. Animal Genetics 41, 346-356.
Riggio, V., Matika, O., Pong-Wong, R., Stear, M.J., Bishop, S.C., 2013. Genome-wide association and regional heritability mapping to identify loci underlying variation in nematode resistance and body weight in Scottish Blackface lambs. Heredity 110, 420-429.
Ruiz-Larrañaga, O., Asadollahpour Nanaei, H., Montes , I., Ayatollahi Mehrgardi, A., Abdolmohammadi, A., Kharrati-Koopaee, H., Sohrabi, S., Rendo, F., Manzano, C., Estonba, A., Iriondo, M., Esmailizadeh, A., 2017. Genetic structure of Iranian indigenous sheep breeds: insights for conservation. Tropical Animal Health and Production 52, 2283-2290.
Signer-Hasler, H., Burren, A., Ammann, P., Drogem uller, C. Flury, C., 2019. Runs of homozygosity and signatures of selection: a comparison among eight local Swiss sheep breeds. Animal Genetics 50, 512-525.
Silió, L., Rodríguez M.C., Fernández, A., Barragán, C., Benítez. R., Óvilo, C., 2013. Measuring inbreeding and inbreeding depression on pig growth from pedigree or SNP-derived metrics. Journal of Animal Breeding and Genetics 130, 349-360.
Solkner, J., Ferencakovic, M., Gredler, B. Curik, I., 2010 Genomic metrics of individual autozygosity, applied to a cattle population. Proceedings of the 61st Annual Meeting of the European Association of Animal Production. Heraklion, Greece.
Sulayman, A., Tursun, M., Sulaiman, Y., Huang, X., Tian, K., Tian. Y., Tulafu, H., 2018. Association analysis of polymorphisms in six keratin genes with wool traits in sheep. Asian-Australasian Journal of Aanimal Sciences 31, 775-783.
Thompson, E.A., 2013. Identity by Descent: Variation in Meiosis, Across Genomes, and in Populations. Genetics 194, 301-326.
VanRaden, P.M., Olson, K.M., Wiggans, G.R., Cole, J.B., Tooker, M. E., 2011. Genomic inbreeding and relationships among Holsteins, Jerseys, and Brown Swiss. Journal of Dairy Science 94, 5673-5682.
Wan, L., Ma, J., Wang, N., Wang, D., Xu, G., 2013. Molecular Cloning and Characterization of Different Expression of MYOZ and MYOZ3 in Tianfu Goat. PLoS ONE 12: e82550.
Wright, S., 1992. Coefficients of inbreeding and relationship. American Naturalist 56, 330-338.
Yang, J.A., Lee, S.H., Goddard, M.E., Visscher, P.M., 2011. GCTA: a tool for genome-wide complex trait analysis. American Journal of Human Genetics 88,76-82.
Zavarez, L.B., Utsunomiya, Y.T., Carmo, A.S., Neves, H.H., Carvalheiro, R., Ferenčaković, M., Pérez O'Brien, A.M., Curik, I., Cole, J.B., Van Tassell, C.P., da Silva, M.V., Sonstegard, T.S., Sölkner, J., Garcia, J.F., 2015. Assessment of autozygosity in Nellore cows (Bos indicus) through high-density SNP genotypes. Frontiers in Genetics 6, 1-8.
Zhang, Q., Calus, M.P., Guldbrandtsen, B., Lund, M.S. Sahana, G., 2015. Estimation of inbreeding using pedigree, 50k SNP chip genotypes and full sequence data in three cattle breeds. BMC Genetics 16, 88-99.