YASEMİN ÖNER, ONUR YILMAZ, Hayrettin OKUT, NEZİH ATA, GÜLNAZ MECİTOĞLU, ABDULKADİR KESKİN

Associations Between GH, PRL, STAT5A, OPN, PIT-1, LEP and FGF2 Polymorphisms and Fertility in Holstein-Friesian Heifers

Bu çalışmada sütçü düvelerde reprodüktif özellikler ile ilişkili yedi gendeki (GH, PRL, STAT5A, OPN, PIT-1, LEP ve FGF2) polimorfizimlerin araştırılması amaçlanmıştır. Genotip frekanslarının fertil ve repeat breeder düve gruplarındaki dağılımı araştırılmıştır. Ayrıca fertilite üzerine allel etkisi de incelenmiştir. Toplam 160 Holstein-Friesian düveden kan alınmış ve bu düveler tohumlama sayılarına (ST) göre iki gruba ayrılmıştır. İlk tohumlamada gebe kalan düveler fertil düve (FH, n=80) olarak kullanılmış ve üç veya daha fazla ST'si olan düveler repeat breeder düve (RBH, n=80) olarak kabul edilmiştir. Tüm hayvanlar yedi gen bakımından PCR-RFLP metodu ile genotiplendirilmiş ve ilişkilendirme çalışmaları toplam 145 hayvanda yapılmıştır (RBH, n=79; FH, n=66). İki allel ve iki genotipin bulunduğu PRL hariç incelenen tüm lokuslarda iki allel ve üç genotip belirlenmiştir. Ki-kare sonuçları (?2) tüm populasyonun ve ayrı ayrı grupların Hardy-Weinberg dengesinde olduğunu ortaya koymuştur. PIT-1 ve STAT5A lokuslarının genotip frekanslarının dağılımları FH ve RBH grupları arasında belirgin biçimde farklı olmasına rağmen bu farklılık istatistiksel anlamda önemli bulunmamıştır. GH-AB genotipinin fertilite üzerine etkisi önemli bulunmuştur. Fertilite üzerindeki allel etkisini incelemek için karışık etkili lojistik regresyon analizi kullanılmıştır. İncelenen lokuslar arasında bir bağlantı dengesizliği belirlenmemiştir

Holstein-Friesian Düvelerde Fertilite ile GH, PRL, STAT5A, OPN, PIT-1, LEP ve FGF2 Polimorfizimlerinin İlişkileri

In this study, it was aimed to investigate polymorphisms in seven genes (GH, PRL, STAT5A, OPN, PIT-1, LEP and FGF2) related to reproductive traits in dairy heifers. Frequency distributions of the genotypes between fertile and repeat breeder heifers groups were investigated. Allele effects on fertility were also analyzed. Blood samples were taken from a total of 160 Holstein-Friesian heifers and they were divided into two groups according to their artificial insemination numbers (AI). The heifers becoming pregnant after the first AI were used as the fertile heifers (FH, n=80) and the heifers with 3 or more equal AIs were accepted as the repeat breeder heifers (RBH, n=80). All the animals were genotyped by the PCR-RFLP method for seven genes and the association works were performed for 145 animals (RBH, n=79; FH n=66). For all loci investigated, two alleles and three genotypes were found for overall population with the exception that PRL locus had two alleles and two genotypes. The chi-square test (χ2) revealed that the whole population and the two groups separately were at Hardy-Weinberg equilibrium. The genotype distributions of PIT-1 and STAT5A conspicuously differed between the FH and the RBH groups; however, these differences were not found significant. Association of GH-AB genotype was found significant on AI number for the first pregnancy. Mixed effect logistic regression model was used to investigate the allele effects on fertility. No linkage disequilibrium was detected between the investigated loci

PDF

___

1. Royal M, Mann GE, Flint AP: Strategies for reversing the trend towards subfertility in dairy cattle. Vet J, 160, 53-60, 2000. DOI: 10.1053/ tvjl.1999.0450
2. Lucy MC: Reproductive loss in high-producing dairy cattle: where will it end? J Dairy Sci, 84, 1277-1293, 2001. DOI: 10.3168/jds.S0022- 0302(01)70158-0
3. Thatcher WW, Bilby TR, Bartolome JA, Silvestre F, Staples CR, Santos JEP: Strategies for improving fertility in the modern dairy cow. Theriogenology, 65, 30-44, 2006. DOI: 10.1016/j.theriogenology.2005.10.004
4. Hayes BJ, Bowman PJ, Chamberlain AJ, Goddard ME: Invited review: Genomic selection in dairy cattle: Progress and challenges. J Dairy Sci, 92, 433-443, 2009. DOI: 10.3168/jds.2008-1646
5. Khatib H, Huang W, Wang X, Tran AH, Bindrim AB, Schutzkus V, Monson RL, Yandell BS: Single gene and gene interaction effects on fertilization and embryonic survival rates in cattle. J Dairy Sci, 92, 2238- 2247, 2009a. DOI: 10.3168/jds.2008-1767
6. Michael DD, Alvarex IM, Ocón OM, Powell AM, Talbot NC, Johnson SE, Ealy AD: Fibrobl3ast growth factor-2 is expressed by the bovine uterus and stimulates interferon-tau production in bovine trophectoderm. Endocrinology, 147, 3571-3579, 2006. DOI: 10.1210/en.2006-0234
7. Chelmanska-Soyta A: Interferon tau and its immunobiological role in ruminant reproduction. Arc Immunol Ther Exp, 50 (1): 47-52, 2002.
8. Woollard J, Tuggle CK, Leon FAP: Rapid communication: Localization of POU1F1 to bovine, ovine, and caprine 1q21-22. Anim Sci, 78, 242-243, 2000.
9. Bastos E, Santos I, Parmentier I, Castrillo JL, Cravador A, GuedesPinto H, Renaville R: Ovis aries POU1F1 gene: Cloning, characterization and polymorphism analysis. Genetica, 126, 303-314, 2006. DOI: 10.1007/s10709- 005-0034-6
10. Feuermann Y, Mabjeesh SJ, Shamay A: Leptin affects prolactin action on milk protein and fat synthesis in the bovine mammary gland. J Dairy Sci, 87, 2941-2946, 2004. DOI: 10.3168/jds.S0022-0302(04)73425-6
11. Kerr JM, Fisher LW, Termine JD, Young MF: The cDNA cloning and RNA distribution of bovine osteopontin. Gene, 108, 237-243, 1991. DOI: 10.1016/0378-1119(91)90439-I
12. Denhardt DT, Noda M, O’Regan AW, Pavlin D, Berman JS: Osteopontin as a means to cope with environmental insults: Regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest, 107, 1055-1061, 2001. DOI: 10.1172/JCI12980
13. Schindler C, Darnell JE: Transcriptional responses to polypeptide ligands. The JAK-STAT pathway. Annu Rev Biochem, 64, 621-651, 1995. DOI: 10.1146/annurev.bi.64.070195.003201
14. Seyfert H, Pitra C, Meyer L, Brunner RM, Wheeler TT, Molenaar A, McCracken JY, Herrmann J, Thiesen H, Schwerin M: Molecular characterization of STAT5A- and STAT5B-encoding genes reveals extended intragenic sequence homogeneity in cattle and mouse and different degrees of divergent evolution of various domains. J Mol Evol, 50 (6): 550-561, 2000. DOI: 10.1007/s002390010058
15. Selvaggi M, Dario C, Normanno G, Celano GV, Dario M: Genetic polymorphism of STAT5A protein: relationships with production traits and milk composition in Italian Brown cattle. J Dairy Res, 76, 441-445, 2009. DOI: 10.1017/S0022029909990070
16. Hallerman EM, Theilmann JL, Beckmann JS, Soller M, Womack JE: Mapping of bovine prolactin and rhodopsin genes in hybrid somatic cells. Anim Genet, 19, 123-131, 1988. DOI: 10.1111/j.1365-2052.1988. tb00798.x
17. Båge R, Gustafson H, Lasson B, Forsberg M, Rodríguez-Martínez H: Repeat-breeding in dairy heifers: Follicular dynamics and estrus cycle characteristics in relation to sexual hormone patterns. Theriogenology, 57, 2257-2269, 2002. DOI: 10.1016/S0093-691X(02)00840-3
18. Oikonomou G, Michailidis G, Kougioumtzis A, Avdi M, Banos G: Effect of polymorphisms at the STAT5A and FGF2 gene loci on reproduction, milk yield and lameness of Holstein cows. Res Vet Sci, 91, 235-239, 2011. DOI: 10.1016/j.rvsc.2011.01.009
19. Khatib H, Maltecca C, Monson RL, Schutzkus V, Wang X, Rutledge JJ: The fibroblast growth factor 2 gene is associated with embryonic mortality in cattle. J Anim Sci, 86, 2063-2067, 2008. DOI: 10.2527/jas.2007- 0791
20. Leonard S, Khatib H, Schutzkus V, Chang YM, Maltecca C: Effects of the osteopontin gene variants on milk production traits in dairy cattle. J Dairy Sci, 88, 4083-4086, 2005. DOI: 10.3168/jds.S0022-0302(05)73092-7
21. Woollard J, Schmitz CB, Freeman AE, Tuggle CK: Rapid communication: HinfI polymorphism at the bovine Pit-1 locus. J Anim Sci, 72, 3267, 1994.
22. Khatib H, Monson RL, Schutzkus V, Kohl DM, Rosa GJM, Rutledge JJ: Mutations in the STAT5A gene are associated with embryonic survival and milk composition in cattle. J Dairy Sci, 91,784-793, 2008. DOI: 10.3168/ jds.2007-0669
23. Lagziel A, Lipkin E, Ezra E, Soller M, Weller JI: An MspI polymorphism at the bovine growth hormone (bGH) gene is linked to a locus affecting milk protein percentage. Anim Genet, 30 (4): 296-299, 1999.
24. Brym P1, Kamiński S, Wójcik E: Nucleotide sequence polymorphism within exon 4 of the bovine prolactin gene and its associations with milk performance traits. J Appl Genet, 45 (2): 179-185, 2005.
25. Rasor CC, Thomas MG, Enns RM, Salazar HC, Zhang HM, Williams GL, Stanko RL, Randel RD, Rios J: Allelic and Genotypic frequencies of the leptin gene sau3ai restriction fragment length polymorphism and evaluation of its association with age at puberty in cattle in the Southwestern United States and Northern Mexico. PAS, 18, 141-146, 2002. DOI: 10.15232/S1080-7446(15)31502-3
26. Yeh FC, Yang RC, Boyle TBJ, Ye ZH, Mao JX: POPGENE the userfriendly shareware for population genetic analysis. University of Alberta, Canada, 1997.
27. Weir BS: Inferences about linkage disequilibrium. Biometrics, 35, 235- 254, 1979. DOI: 10.2307/2529947
28. Levene H: On a matching problem in genetics. Ann Math Stat, 20, 91-94, 1949.
29. SAS 2002 User Guides: Version 9.2, Carry NC, USA, SAS Instute, Inc. 30. Zhang C, Liu B, Chen H, Lan X, Lei C, Zhang Z, Zhang R: Associations of a hinfI PCR-RFLP of POU1F1 gene with Growth Traits in Qinchuan cattle. Anim Biotechnol, 20, 71- 74, 2009. DOI: 10.1080/10495390802640462
31. Zakizadeh S, Reissmann M, Rahimi G, Javaremi AN, Reinecke P, Mirae-Ashtiani SR, Shahrbabak MM: Polymorphism of bovine POU1F1 gene: Allele frequencies and effects on milk production in three Iranian native breeds and Holstein cattle of Iran. Pak J Biol Sci, 10 (15): 2575-2578, 2007.
32. Aytekin I, Boztepe S: Associations of Pit-1 gene polymorphism with milk yield and composition traits in brown swiss cattle. JAPS, 23, 1281- 1289, 2013.
33. Pasandideh M, Mohammadabadi MR, Esmailizadeh AK, Tarang A: Association of bovine PPARGC1A and OPN genes with milk production and composition in Holstein cattle. Czech J Anim Sci, 60, 97-104, 2015. DOI: 10.17221/7975-CJAS
34. Kowalewska-Łuczak I, Kulig H: Genetic polymorphisms of FAM13A1, OPN, LAP3, and HCAP-G genes in Jersey cattle. Turk J Vet Anim Sci, 37, 631-635, 2013. DOI: 10.3906/vet-1105-3
35. Mitra A, Schlee P, Balakrishnan CR, Pirchner F: Polymorphism at growth hormone and prolactin loci in Indian cattle and buffalo. J Anim Breed Genet, 112, 71-74, 1995. DOI: 10.1111/j.1439-0388.1995.tb00543.x
36. Udina IG, Turkova SO, Kostyuchenko MV, Lebedeva A, Sulimova GE: Polymorphism of bovine prolactin gene: Microsatellites, PCR-RFLP. Russ J Genet, 37, 407-411, 2001. DOI: 10.1023/A:1016654410191
37. Khatib H, Maltecca C, Monson RL, Schutzkus V, Rutledge JJ: Monoallelic maternal expression of STAT5A affects embryonic survival in cattle. BMC Genet, 10, 13, 2009b. DOI: 10.1186/1471-2156-10-13
38. Boleckova J, Matejickova J, Stipkova M, Kyselova J, Barton L: The association of five polymorphisms with milk production traits in Czech Fleckvieh cattle. Czech J Anim Sci, 57 (2): 45-53, 2012.
39. Nkrumah JD, Li C, Yu J, Hansen C, Keisler DH, Moore SS: Polymorphism in the bovine leptin gene promoter associated with serum leptin concentration, growth, feed intake, feeding behavior, and measures of carcass merit. J Anim Sci, 83, 20-28, 2005. DOI: 10.2527/2005.83120x
40. Giblin L, Butler ST, Kearney BM, Waters SM, Callanan MJ, Berry DP: Association of bovine leptin polymorphisms with energy output and energy storage traits in progeny tested Holstein-Friesian dairy cattle sires. BMC Genet, 11, 73, 2010. DOI: 10.1186/1471-2156-11-73
41. Mappanganro R, Rahardja DP, Sonjaya H: Relationship between leptin gen with body condition score Bali cows and cross-bred. J Sains Teknologi, 14 (3): 232- 240, 2014.
42. Zwierzchowski L, Krzyżewski J, Strzałkowska N, Siadkowska E, Ryniewicz Z: Effects of polymorphism of growth hormone (GH), Pit-1, and leptin (LEP) genes, cow’s age, lactation stage, and somatic cell count on milk yield and composition of Polish Black-and White cows. Anim Sci Pap Rep, 20 (4): 213-227, 2002.
43. Hayhurst C, Sørensen MK, Royal MD, Løvendahl P: Metabolic regulation in Danish bull calves and the relationship to the fertility of their female offspring. J Dairy Sci, 90, 3909-3916, 2007. DOI: 10.3168/ jds.2006-731
44. Mullen MP, Lynch CO, Waters SM, Howard DJ, O’Boyle P, Kenny DA, Buckley F, Horan B, Diskin MG: Single nucleotide polymorphisms in the growth hormone and insulin-like growth factor-1 genes are associated with milk production, body condition score and fertility traits in dairy cows. Genet Mol Res, 10, 1819-1830, 2011. DOI: 10.4238/vol10- 3gmr1173
45. Dybus A: Associations of growth hormone (GH) and prolactin (PRL) genes polymorphisms with milk production traits in Polish Black-andWhite cattle. Anim Sci Pap Rep, 20, 203-212, 2002.
46. Hoj S, Fredholm M, Larsen NJ, Nielsen VH: Growth hormone gene polymorphism associated with selection for milk fat production in lines of cattle. Anim Genet, 24, 91-96, 1993. DOI: 10.1111/j.1365-2052.1993. tb00246.x
47. Lucy MC, Hauser SD, Eppard PJ, Krivi GG, Clark JH, Bauman DE, Collier RJ: Variants of somatotropin in cattle: Gene frequencies in major dairy breeds and associated milk production. Domest Anim Endocrinol, 10(4), 325-333, 1993. DOI: 10.1016/0739-7240(93)90036-B
48. Unanian MM, Barreto CC, Cordeiro CMT, Freitas AR, Josahkian LA: Possible association between bovine growth hormone gene polymorphism and reproductive traits. Braz Arch Biol Technol, 45, 293-299, 2002. DOI: 10.1590/S1516-89132002000300007
49. Gorbani A, Torshizi RV, Bonyadi M, Amirinia C: Restriction fragment length polymorphism of bovine growth hormone gene intron 3 and its association with testis biometry traits in Iranian Holstein bull. Afc J Microbiol Res, 3 (11): 809-814, 2009.
50. Arango J, Echeverri JJ, López A: Association between a polymorphism in intron 3 of the bovine growth hormone gene and growth traits in Holstein heifers in Antioquia. Genet Mol Res, 13, 6191-6199, 2014. DOI: 10.4238/2014.August.15.1
51. Lagziel A, Denise S, Hanotte O, Dhara S, Glazko V, Broadhead A, Davoli R, Russo V, Soller M: Geographic and breed distribution of an MspI PCR-RFLP in the bovine growth hormone (bGH) gene. Anim Genet, 31, 210-213, 2000. DOI: 10.1046/j.1365-2052.2000.00622.x
52. Sodhi M, Mukesh M, Prakash, B, Mishra B, Sobti, R, Karn S, Singh S, Ahlawat S: MspI allelic pattern of bovine growth hormone gene in Indian Zebu cattle (Bos indicus) breeds. Biochem Genet, 45, 145-153, 2007. DOI: 10.1007/s10528-006-9068-4
53. Korkmaz Agaoglu Ö, Akyuz B: Growth hormone gene polymorphism in four cattle breeds in Turkey. Kafkas Univ VetFak Derg, 19, 419-422, 2013. DOI: 10.9775/kvfd.2012.7961
54. Akyuz B, Arslan K, Bayram D, İşcan KM: Allelic frequency of kappakasein, growth hormone and prolactin gene in Holstein, Brown Swiss and Simmental cattle breeds in Turkey. Kafkas Univ VetFak Derg, 19, 439-444, 2013 DOI: 10.9775/kvfd.2012.7985