Genomic inbreeding estimation, runs of homozygosity, and heterozygosity-enriched regions uncover signals of selection in the Quarter Horse racing line.
Abstract: With the advent of genomics, significant progress has been made in the genetic improvement of livestock species, particularly through increased accuracy in predicting breeding values for selecting superior animals and the possibility of performing a high-resolution genetic scan throughout the genome of an individual. The main objectives of this study were to estimate the individual genomic inbreeding coefficient based on runs of homozygosity (F ), to identify and characterize runs of homozygosity and heterozygosity (ROH and ROHet, respectively; length and distribution) throughout the genome, and to map selection signatures in relevant chromosomal regions in the Quarter Horse racing line. A total of 336 animals registered with the Brazilian Association of Quarter Horse Breeders (ABQM) were genotyped. One hundred and twelve animals were genotyped using the Equine SNP50 BeadChip (Illumina, USA), with 54,602 single nucleotide polymorphisms (SNPs; 54K). The remaining 224 samples were genotyped using the Equine SNP70 BeadChip (Illumina, USA) with 65,157 SNPs (65K). To ensure data quality, we excluded animals with a call rate below 0.9. We also excluded SNPs located on non-autosomal chromosomes, as well as those with a call rate below 0.9 or a p-value below 1 × 10 for Hardy-Weinberg equilibrium. The results indicate moderate to high genomic inbreeding, with 46,594 ROH and 16,101 ROHet detected. In total, 30 and 14 candidate genes overlap with ROH and ROHet regions, respectively. The ROH islands showed genes linked to crucial biological processes, such as cell differentiation (CTBP1, WNT5B, and TMEM120B), regulation of glucose metabolic process (MAEA and NKX1-1), heme transport (PGRMC2), and negative regulation of calcium ion import (VDAC1). In ROHet, the islands showed genes related to respiratory capacity (OR7D19, OR7D4G, OR7D4E, and OR7D4J) and muscle repair (EGFR and BCL9). These findings could aid in selecting animals with greater regenerative capacity and developing treatments for muscle disorders in the QH breed. This study serves as a foundation for future research on equine breeds. It can contribute to developing reproductive strategies in animal breeding programs to improve and preserve the Quarter Horse breed.
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This study explores the genetic attributes of the Quarter Horse racing line using genomics to work towards improving and preserving the breed. Researchers conducted a detailed scan of the genome of these horses to estimate genomic inbreeding coefficients, identify runs of homozygosity and heterozygosity, and map selection signatures on chromosomes.
Overview of the Study
The main goal of this research was to estimate the individual genomic inbreeding coefficient based on runs of homozygosity (ROH), identify and outline the nature (length and distribution) of ROH and heterozygosity (ROHet), and map selection patterns in the Quarter Horse racing line’s relevant chromosomal regions.
The researchers analyzed the genomes of 336 animals registered with the Brazilian Association of Quarter Horse Breeders.
Two types of SNP BeadChips (Genotyping panels) were used, one with 54,602 single nucleotide polymorphisms (SNPs) for 112 animals and another with 65,157 SNPs for the remaining 224 samples. This was done to extract high quality, comprehensive genomic data.
Quality Assurance
Only animals with a high-quality call rate (above 0.9) were included in the study.
SNPs located on non-autosomal chromosomes were excluded, along with those with a low call rate or unsatisfactory Hardy-Weinberg equilibrium p-value.
Findings
The study identified a moderate to high level of genomic inbreeding, along with 46,594 runs of homozygosity and 16,101 runs of heterozygosity.
In total, 30 and 14 candidate genes overlapped with the respective ROH and ROHet regions.
The ROH islands demonstrated genes linked to crucial biological processes such as glucose metabolic regulation, cell differentiation, heme transport, and the negative regulation of calcium ion import.
The ROHet islands showed genes linked to respiratory capacity and muscle repair, indicating potential areas of focus for improving regenerative capacity in these horses and developing treatments for muscle disorders in the Quarter Horse breed.
Implications
This study has implications for the development of reproductive strategies in animal breeding programs aimed at improving and preserving the Quarter Horse breed.
It lays a foundation for more comprehensive future research on equine breeds and their genetics.
Cite This Article
APA
Santos WB, Pereira CB, Maiorano AM, Arce CDS, Baldassini WA, Pereira GL, Chardulo LAL, Neto ORM, Oliveira HN, Curi RA.
(2023).
Genomic inbreeding estimation, runs of homozygosity, and heterozygosity-enriched regions uncover signals of selection in the Quarter Horse racing line.
J Anim Breed Genet.
https://doi.org/10.1111/jbg.12812
ABQM. (2019). Associação brasileira dos criadores de cavalos Quarto de Milha [webpage]. Retrieved from https://www.abqm.com.br
Al-Mamun HA, Clark SA, Kwan P, Gondro C. Genome-wide linkage disequilibrium and genetic diversity in five populations of Australian domestic sheep. Genetics Selection Evolution 47, 90 (2015).
Bertolini F, Servin B, Talenti A, Rochat E, Kim ES, Oget C, Palhière I, Crisà A, Catillo G, Steri R, Amills M, Colli L, Marras G, Milanesi M, Nicolazzi E, Rosen BD, Van Tassell CP, Guldbrandtsen B, Sonstegard TS, AdaptMap consortium. Signatures of selection and environmental adaptation across the goat genome post- domestication. Genetics Selection Evolution 50(1), 57 (2018).
Biscarini F, Cozzi P, Gaspa G, Marras G. detectRUNS: Detect runs of homozygosity and runs of heterozygosity in diploid genomes. .
Brack AS, Murphy-Seiler F, Hanifi J, Deka J, Eyckerman S, Keller C, Aguet M, Rando TA. BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration. Developmental Biology 335, 93-105 (2009).
Calaf GM, Crispin LA, Muñoz JP, Aguayo F, Roy D, Narayan G. Ionizing radiation and estrogen affecting growth factor genes in an experimental breast cancer model. International Journal of Molecular Sciences 23, 14284 (2022).
Curik I, Ferencakovic M, Solkner J. Genomic dissection of inbreeding depression: A gate to new opportunities. Brazilian Journal of Animal Science 46, 773-782 (2017).
Harris AM, DeGiorgio M. An unbiased estimator of gene diversity with improved variance for samples containing related and inbred individuals of any ploidy. G3 (Bethesda) G3(9), 671-691 (2017).
Howrigan D, Simonson M, Keller M. Detecting autozygosity through runs of homozygosity: A comparison of three autozygosity detection algorithms. BMC Genomics 12, 460 (2011).
Jetten AM. GLIS1-3 transcription factors: Critical roles in the regulation of multiple physiological processes and diseases. Cellular and Molecular Life Sciences 75, 3473-3494 (2018).
Ji R, Xu X, Turchini MG, Mai K, Ai Q. Adiponectin's roles in lipid and glucose metabolism modulation in fish: Mechanisms and perspectives. Reviews in Aquaculture 13, 2305-2321 (2021).
Jombart T, Devillard S, Balloux F. Discriminant analysis of principal components: A new method for the analysis of genetically structured populations. BMC Genetics 11, 94 (2010).
Keller MC, Visscher PM, Goddard ME. Quantification of inbreeding due to distant ancestors and its detection using dense single nucleotide polymorphism data. Genetics 189, 237-249 (2011).
Lima RAS, Shirota R, Barros GSC. Estudo do Complexo do Agronegócio Cavalo no Brasil. Centro de Estudos Avançados em Economia Aplicada - CEPEA (2006).
Llaurens V, Whibley A, Joron M. Genetic architecture and balancing selection: The life and death of differentiated variants. Molecular Ecology 26, 2430-2448 (2017).
López-Cortegano E, Pouso R, Labrador A, Pérez-Figueroa A. Optimal Management of Genetic Diversity in subdivided populations. Frontiers in Genetics 10, 843 (2019).
Mancin E, Ablondi M, Mantovani R, Pigozzi G, Sabbioni A, Sartori C. Genetic variability in the Italian heavy draught horse from pedigree data and genomic information. Animals 10, 1310 (2020).
Marchiori C, Pereira GL, Maiorano AM, Rogatto GM, Assoni AD, Silva JVA, Chardulo LAL, Curi RA. Linkage disequilibrium and population structure characterization in the cutting and racing lines of quarter horses bred in Brazil. Livestock Science 219, 45-51 (2019).
Marras G, Gaspa G, Sorbolini S, Dimauro C, Ajmone-Marsan P, Valentini A, Williams JL, Macciotta NPP. Analysis of runs of homozygosity and their relationship with inbreeding in five cattle breeds farmed in Italy. Animal Genetics 46, 110-121 (2015).
Marras G, Wood BJ, Makanjuola B, Malchiodi F, Peeters K, Van As P, Baes CF, Biscarini F, Turkeys H. Characterization of runs of homozygosity and heterozygosity-rich regions in a commercial Turkey (Meleagris gallopavo) population. Proceedings of the World Congress on Genetics Applied to Livestock Production 11, 763 (2017).
Mc Parland S, Kearney F, Berry DP. Purging of inbreeding depression within the Irish Holstein-Friesian population. Genetics Selection Evolution 41, 16 (2009).
McQuillan R, Leutenegger AL, Abdel-Rahman R, Franklin CS, Pericic M, Barac-Lauc L, Smolej-Narancic N, Janicijevic B, Polasek O, Tenesa A, MacLeod AK, Farrington SM, Rudan P, Hayward C, Vitart V, Rudan I, Wild SH, Dunlop MG, Wright AF, Wilson JF. Runs of homozygosity in European populations. The American Journal of Human Genetics 83, 359-372 (2008).
Meira CT, Curi RA, Silva JAIIV, Correa MJM, de Oliveira HN, da Mota MD. Morphological and genomic differences between cutting and racing lines of quarter horses. Journal of Equine Veterinary Science 33, 244-249 (2013).
Pemberton TJ, Absher D, Feldman MW, Myers RM, Rosenberg NA, Li JZ. Genomic patterns of homozygosity in worldwide human populations. The American Journal of Human Genetics 91, 275-292 (2012).
Penn DJ, Damjanovich K, Potts WK. MHC heterozygosity confers a selective advantage against multiple-strain infections. Proceedings of the National Academy of Sciences of the United States of America 99, 11260-11264 (2002).
Pereira GL, Chud TCS, Bernardes PA, Venturini GV, Chardulo LA, Curi RA. Genotype imputation and accuracy evaluation in racing quarter horses genotyped using different commercial SNP panels. Journal of Equine Veterinary Science 58, 89-96 (2017).
Rebelato AB, Caetano AR. Runs of homozygosity for autozygosity estimation and genomic analysis in production animals. Pesquisa Agropecuária Brasileira 53, 975-984 (2018).
Rouillard AD, Gundersen GW, Fernandez NF, Wang Z, Monteiro CD, McDermott M, Ma'ayan A. The harmonizome: A collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database 2016, baw100 (2016).
Ruan D, Yang J, Zhuang Z, Ding R, Huang J, Quan J, Gu T, Hong L, Zheng E, Li Z, Cai G, Wang X, Wu Z. Assessment of heterozygosity and genome-wide analysis of heterozygosity regions in two duroc pig populations. Frontiers in Genetics 12, 812456 (2022).
Sakamoto T, Innan H. The evolutionary dynamics of a genetic barrier to gene flow: From the establishment to the emergence of a peak of divergence. Genetics 212(4), 1383-1398 (2019).
Samuels DC, Wang J, Ye F, He J, Levinson RT, Sheng Q, Zhao S, Capra JA, Shyr Y, Zheng W, Guo Y. Heterozygosity ratio, a robust global genomic measure of autozygosity and its association with height and disease risk. Genetics 204, 893-904 (2016).
Sargolzaei M, Chesnais JP, Schenkel FS. A new approach for efficient genotype imputation using information from relatives. BMC Genomics 15, 478 (2014).
Sun J, Have CT, Hollensted M, Grarup N, Linneberg A, Pedersen O, Nielsen JS, Rungby J, Christensen C, Brandslund I, Kristiansen K, Jun W, Hansen T, Gjesing AP. Sequencing reveals protective and pathogenic effects on development of diabetes of rare GLIS3 variants. PLoS One 14, e0220805 (2019).
Szpiech ZA, Xu J, Pemberton TJ, Peng W, Zöllner S, Rosenberg NA, Li JZ. Long runs of homozigosity are enriched for deleteriuos variation. The American Journal of Human Genetics 93, 90-102 (2013).
Williams JL, Hall SJ, Del Corvo M, Ballingall KT, Colli LI, Ajmone Marsan PA, Biscarini F. Inbreeding and purging at the genomic level: The Chillingham cattle reveal extensive, non-random SNP heterozygosity. Animal Genetics 47, 19-27 (2016).
Zhang Q, Guldbrandtsen B, Bosse M, Lund MS, Sahana G. Runs of homozygosity and distribution of functional variants in the cattle genome. BMC Genomics 16, 542 (2015).
Zhao HF, Zhou XM, Wang J, Chen FF, Wu CP, Diao PY, Cai LR, Chen L, Xu YW, Liu J, Li ZY, Liu WL, Chen ZP, Huang GD, Li WP. Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients. Journal of Translational Medicine 19, 372 (2021).
Zheng W, Huang L, Huang J, Wang X, Chen X, Zhao J, Guo J, Zhuang H, Qiu C, Liu J, Liu H, Huang X, Pei G, Zhan G, Tang C, Cheng Y, Liu M, Zhang J, Zhao Z, Kang Z. High genome heterozygosity and endemic genetic recombination in the wheat stripe rust fungus. Nature Communications 4, 2673 (2013).
Maxman G, van Marle-Köster E, Lashmar SF, Visser C. Selection signatures associated with adaptation in South African Drakensberger, Nguni, and Tuli beef breeds. Trop Anim Health Prod 2024 Dec 27;57(1):13.
Falchi L, Cesarani A, Criscione A, Hidalgo J, Garcia A, Mastrangelo S, Macciotta NPP. Effect of genotyping density on the detection of runs of homozygosity and heterozygosity in cattle. J Anim Sci 2024 Jan 3;102.