Animal Reproduction (AR)
https://animal-reproduction.org/article/doi/10.1590/1984-3143-AR2023-0110
Animal Reproduction (AR)
ORIGINAL ARTICLE

Genome-wide association study of Nelore and Angus heifers with low and high ovarian follicle counts

Bárbara Loureiro; Ronaldo Luiz Ereno; Antônio Guilherme Roncada Pupulim; Maria Clara Viana Barroso Tramontana; Henrique Passos Tabosa; Ciro Moraes Barros; Maurício Gomes Favoreto

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Abstract

Abstract: The number of antral follicles is considered an important fertility trait because animals with a high follicle count (HFC) produce more oocytes and embryos per cycle. Identification of these animals by genetic markers such as single nucleotide polymorphisms (SNPs) can accelerate selection of future generations. The aim of this study was to perform a genome wide association study (GWAS) on Nelore and Angus heifers with HFC and low (LFC) antral follicle counts. The groups HFC and LFC for genotyping were formed based on the average of total follicles (≥ 3 mm) counted in each breed consistently ± standard deviation. A total of 72 Nelore heifers (32 HFC and 40 LFC) and 48 Angus heifers (21 HFC and 27 LFC) were selected and the DNA was extracted from blood and hair bulb. Genotyping was done using the Illumina Bovine HD 770K BeadChip. The GWAS analysis showed 181 and 201 SNPs with genotype/phenotype association (P ≤ 0.01) in Nelore and Angus heifers, respectively. Functional enrichment analysis was performed on candidate genes that were associated with SNPs. A total of 97 genes were associated to the 181 SNPs in the Nelore heifers and the functional analysis identified genes (ROBO1 and SLIT3) in the ROBO-SLIT pathway that can be involved in the control of germ cell migration in the ovary as it is involved in lutheal cell migration and fetal ovary development. In the Angus heifers, 57 genes were associated with the 201 SNPs, highlighting Fribilin 1 (FBN1) gene, involved in regulation of growth factors directly involved in follicle activation and development. In summary, GWAS for Nelore and Angus heifers showed SNPs associated with higher follicle count phenotype. Furthermore, these findings offer valuable insights for the further investigation of potential mechanism involved in follicle formation and development, important for breeding programs for both breeds.

Keywords

Bovine HD 770 K SNP, candidate genes, follicle, reproduction, SNPs

References

Aulchenko YS, Ripke S, Isaacs A, van Duijn CM. GenABEL: an R library for genome-wide association analysis. Bioinformatics. 2007;23(10):1294-6. http://dx.doi.org/10.1093/bioinformatics/btm108. PMid:17384015.

Bohmanova J, Sargolzaei M, Schenkel FS. Characteristics of linkage disequilibrium in North American Holsteins. BMC Genomics. 2010;11(1):421. http://dx.doi.org/10.1186/1471-2164-11-421. PMid:20609259.

Bush WS, Chen G, Torstenson ES, Ritchie MD. LD-spline: mapping SNPs on genotyping platforms to genomic regions using patterns of linkage disequilibrium. BioData Min. 2009;2(1):7. http://dx.doi.org/10.1186/1756-0381-2-7. PMid:19954552.

Buzanskas ME, Grossi DA, Ventura RV, Schenkel FS, Chud TCS, Stafuzza NB, Rola LD, Meirelles SLC, Mokry FB, Mudadu MA, Higa RH, Silva MVGB, Alencar MM, Regitano LCA, Munari DP. Candidate genes for male and female reproductive traits in Canchim beef cattle. J Anim Sci Biotechnol. 2017;8(1):67. http://dx.doi.org/10.1186/s40104-017-0199-8. PMid:28852499.

Capra E, Lazzari B, Milanesi M, Nogueira GP, Garcia JF, Utsunomiya YT, Ajmone-Marsan P, Stella A. Comparison between indicine and taurine cattle DNA methylation reveals epigenetic variation associated to differences in morphological adaptive traits. Epigenetics. 2023;18(1):2163363. http://dx.doi.org/10.1080/15592294.2022.2163363. PMid:36600398.

Chamberlain AJ, Hayes BJ, Savin K, Bolormaa S, McPartlan PJ, van de Jagt C, MacEachern S, Goddard ME. Validation of single nucleotide polymorphisms associated with milk production traits in dairy cattle. J Dairy Sci. 2012;95(2):864-75. http://dx.doi.org/10.3168/jds.2010-3786. PMid:22281351.

Clarke GM, Anderson CA, Pettersson FH, Cardon LR, Morris AP, Zondervan KT. Basic statistical analysis in genetic case-control studies. Nat Protoc. 2011;6(2):121-33. http://dx.doi.org/10.1038/nprot.2010.182. PMid:21293453.

Cortez T, Montenegro H, Coutinho LL, Regitano LCA, Andrade SCS. Molecular evolution and signatures of selective pressures on Bos, focusing on the Nelore breed (Bos indicus). PLoS One. 2022;17(12):e0279091. http://dx.doi.org/10.1371/journal.pone.0279091. PMid:36548260.

Cushman RA, Soares EM, Yake HK, Patterson AL, Rosasco SL, Beard JK, Northrop EJ, Rich JJJ, Miles JR, Chase CC Jr, Gonda MG, Perry GA, McNeel AK, Summers AF. Brangus cows have ovarian reserve parameters more like Brahman than Angus cows. Anim Reprod Sci. 2019;209:106170. http://dx.doi.org/10.1016/j.anireprosci.2019.106170. PMid:31514925.

Dar MR, Singh M, Thakur S, Verma A. Exploring the relationship between polymorphisms of leptin and IGF-1 genes with milk yield in indicine and taurine crossbred cows. Trop Anim Health Prod. 2021;53(4):413. http://dx.doi.org/10.1007/s11250-021-02866-1. PMid:34308489.

Dehghan A. Genome-wide association studies. Methods Mol Biol. 2018;1793:37-49. http://dx.doi.org/10.1007/978-1-4939-7868-7_4. PMid:29876890.

Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003;4(5):3. http://dx.doi.org/10.1186/gb-2003-4-5-p3. PMid:12734009.

Devine CA, Key B. Robo-Slit interactions regulate longitudinal axon pathfinding in the embryonic vertebrate brain. Dev Biol. 2008;313(1):371-83. http://dx.doi.org/10.1016/j.ydbio.2007.10.040. PMid:18061159.

Dickinson RE, Hryhorskyj L, Tremewan H, Hogg K, Thomson AA, McNeilly AS, Duncan WC. Involvement of the SLIT/ROBO pathway in follicle development in the fetal ovary. Reproduction. 2010;139(2):395-407. http://dx.doi.org/10.1530/REP-09-0182. PMid:19900988.

Dickinson RE, Myers M, Duncan WC. Novel regulated expression of the SLIT/ROBO pathway in the ovary: possible role during luteolysis in women. Endocrinology. 2008;149(10):5024-34. http://dx.doi.org/10.1210/en.2008-0204. PMid:18566128.

Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature. 1996;383(6600):531-5. http://dx.doi.org/10.1038/383531a0. PMid:8849725.

Ensembl [Internet]. 2023 [cited 2023 Jul 25]. Available from: http://www.ensembl.org/index.html

Favoreto MG, Loureiro B, Ereno RL, Pupulim AG, Queiroz V, Silva NA, Barros CM. Follicle populations and gene expression profiles of Nelore and Angus heifers with low and high ovarian follicle counts. Mol Reprod Dev. 2019;86(2):197-208. http://dx.doi.org/10.1002/mrd.23095. PMid:30537208.

Galvão KN, Federico P, De Vries A, Schuenemann GJ. Economic comparison of reproductive programs for dairy herds using estrus detection, timed artificial insemination, or a combination. J Dairy Sci. 2013;96(4):2681-93. http://dx.doi.org/10.3168/jds.2012-5982. PMid:23415521.

Huang W, Kirkpatrick BW, Rosa GJ, Khatib H. A genome-wide association study using selective DNA pooling identifies candidate markers for fertility in Holstein cattle. Anim Genet. 2010;41(6):570-8. http://dx.doi.org/10.1111/j.1365-2052.2010.02046.x. PMid:20394602.

Hutchison JL, VanRaden P, Null D, Cole J, Bickhart D. Genomic evaluation of age at first calving. J Dairy Sci. 2017;100(8):6853-61. http://dx.doi.org/10.3168/jds.2016-12060. PMid:28624286.

Illumina. GenomeStudio Data Analysis Software. San Diego; 2023.

Ireland JJ, Ward F, Jimenez-Krassel F, Ireland JL, Smith GW, Lonergan P, Evans AC. Follicle numbers are highly repeatable within individual animals but are inversely correlated with FSH concentrations and the proportion of good-quality embryos after ovarian stimulation in cattle. Hum Reprod. 2007;22(6):1687-95. http://dx.doi.org/10.1093/humrep/dem071. PMid:17468258.

Kneeland J, Li C, Basarab J, Snelling WM, Benkel B, Murdoch B, Hansen C, Moore SS. Identification and fine mapping of quantitative trait loci for growth traits on bovine chromosomes 2, 6, 14, 19, 21, and 23 within one commercial line of Bos taurus. J Anim Sci. 2004;82(12):3405-14. http://dx.doi.org/10.2527/2004.82123405x. PMid:15537758.

Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction. 2006;132(2):191-206. http://dx.doi.org/10.1530/rep.1.01074. PMid:16885529.

Liu R, Tearle R, Low WY, Chen T, Thomsen D, Smith TPL, Hiendleder S, Williams JL. Distinctive gene expression patterns and imprinting signatures revealed in reciprocal crosses between cattle sub-species. BMC Genomics. 2021;22(1):410. http://dx.doi.org/10.1186/s12864-021-07667-2. PMid:34082698.

Maiorano AM, Cardoso DF, Carvalheiro R, Fernandes GA Jr, Albuquerque LG, de Oliveira HN. Signatures of selection in Nelore cattle revealed by whole-genome sequencing data. Genomics. 2022;114(2):110304. http://dx.doi.org/10.1016/j.ygeno.2022.110304. PMid:35131473.

McNatty KP, Fidler AE, Juengel JL, Quirke LD, Smith PR, Heath DA, Lundy T, O’Connell A, Tisdall DJ. Growth and paracrine factors regulating follicular formation and cellular function. Mol Cell Endocrinol. 2000;163(1-2):11-20. http://dx.doi.org/10.1016/S0303-7207(99)00235-X. PMid:10963868.

Mossa F, Walsh SW, Butler ST, Berry DP, Carter F, Lonergan P, Smith GW, Ireland JJ, Evans AC. Low numbers of ovarian follicles ≥3 mm in diameter are associated with low fertility in dairy cows. J Dairy Sci. 2012;95(5):2355-61. http://dx.doi.org/10.3168/jds.2011-4325. PMid:22541464.

Mota LFM, Lopes FB, Fernandes GA Jr, Rosa GJM, Magalhães AFB, Carvalheiro R, Albuquerque LG. Genome-wide scan highlights the role of candidate genes on phenotypic plasticity for age at first calving in Nellore heifers. Sci Rep. 2020;10(1):6481. http://dx.doi.org/10.1038/s41598-020-63516-4. PMid:32296097.

Muroya S, Ogasawara H, Hojito M. Grazing affects exosomal circulating MicroRNAs in cattle. PLoS One. 2015;10(8):e0136475. http://dx.doi.org/10.1371/journal.pone.0136475. PMid:26308447.

Naukkarinen J, Surakka I, Pietiläinen KH, Rissanen A, Salomaa A, Ripatti V, Yki-Järvinen H, van Duijn CM, Wichmann HE, Kaprio J, Taskinen MR, Peltonen L. Use of genome-wide expression data to mine the “Gray Zone” of GWA studies leads to novel candidate obesity genes. PLoS Genet. 2010;6(6):e1000976. http://dx.doi.org/10.1371/journal.pgen.1000976. PMid:20532202.

Parker Gaddis KL, Cole J, Clay J, Maltecca C. Genomic selection for producer-recorded health event data in US dairy cattle. J Dairy Sci. 2014;97(5):3190-9. http://dx.doi.org/10.3168/jds.2013-7543. PMid:24612803.

Peñagaricano F, Weigel KA, Khatib H. Genome-wide association study identifies candidate markers for bull fertility in Holstein dairy cattle. Anim Genet. 2012;43(Suppl. 1):65-71. http://dx.doi.org/10.1111/j.1365-2052.2012.02350.x. PMid:22742504.

Pérez-Pardal L, Royo LJ, Beja-Pereira A, Chen S, Cantet RJC, Traore A, Curik I, Sölkner J, Bozzi R, Fernández I, Alvarez I, Gutiérrez JP, Gómez E, Ponce de León FA, Goyache F. Multiple paternal origins of domestic cattle revealed by Y-specific interspersed multilocus microsatellites. Heredity. 2010;105(6):511-9. http://dx.doi.org/10.1038/hdy.2010.30. PMid:20332805.

Pitt D, Sevane N, Nicolazzi EL, MacHugh DE, Park SDE, Colli L, Martinez R, Bruford MW, Orozco-terWengel P. Domestication of cattle: two or three events? Evol Appl. 2018;12(1):123-36. http://dx.doi.org/10.1111/eva.12674. PMid:30622640.

Powell J, Talenti A, Fisch A, Hemmink JD, Paxton E, Toye P, Santos I, Ferreira BR, Connelley TK, Morrison LJ, Prendergast JGD. Profiling the immune epigenome across global cattle breeds. Genome Biol. 2023;24(1):127. http://dx.doi.org/10.1186/s13059-023-02964-3. PMid:37218021.

Ramirez F, Sakai LY. Biogenesis and function of fibrillin assemblies. Cell Tissue Res. 2010;339(1):71-82. PMid:19513754.

Richani D, Gilchrist RB. The epidermal growth factor network: role in oocyte growth, maturation and developmental competence. Hum Reprod Update. 2018;24(1):1-14. http://dx.doi.org/10.1093/humupd/dmx029. PMid:29029246.

Ritter LJ, Sugimura S, Gilchrist RB. Oocyte induction of EGF responsiveness in somatic cells is associated with the acquisition of porcine oocyte developmental competence. Endocrinology. 2015;156(6):2299-312. http://dx.doi.org/10.1210/en.2014-1884. PMid:25849729.

Sakai LY, Keene DR, Glanville RW, Bächinger HP. Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. J Biol Chem. 1991;266(22):14763-70. http://dx.doi.org/10.1016/S0021-9258(18)98752-1. PMid:1860873.

Sengle G, Charbonneau NL, Ono RN, Sasaki T, Alvarez J, Keene DR, Bächinger HP, Sakai LY. Targeting of bone morphogenetic protein growth factor complexes to fibrillin. J Biol Chem. 2008;283(20):13874-88. http://dx.doi.org/10.1074/jbc.M707820200. PMid:18339631.

Verardo LL, Silva FF, Machado MA, Panetto JCC, Faza DRLR, Otto PI, Regitano LCA, Silva LOC, Egito AA, Albuquerque MSM, Zanella R, Silva MVGB. Genome-wide analyses reveal the genetic architecture and candidate genes of indicine, taurine, synthetic crossbreds, and locally adapted cattle in Brazil. Front Genet. 2021;12:702822. http://dx.doi.org/10.3389/fgene.2021.702822. PMid:34386042.

Wald M. Eidermal growth factor and spermatogenesis. J Urol. 2005;174(6):2089-90. http://dx.doi.org/10.1097/01.ju.0000187410.24477.cf. PMid:16280734.

Wong K, Park HT, Wu JY, Rao Y. Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Curr Opin Genet Dev. 2002;12(5):583-91. http://dx.doi.org/10.1016/S0959-437X(02)00343-X. PMid:12200164.

Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL, Celeste AJ, Matzuk MM. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol. 2001;15(6):854-66. http://dx.doi.org/10.1210/mend.15.6.0662. PMid:11376106.

Zhang H, Hu W, Ramirez F. Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils. J Cell Biol. 1995;129(4):1165-76. http://dx.doi.org/10.1083/jcb.129.4.1165. PMid:7744963.
 


Submitted date:
07/25/2023

Accepted date:
12/06/2023

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