The melanocortin-4 receptor (MC4R) is a gene that controls growth traits.  This gene is embedded in the leptin-melanocortin pathway and regulates body weight.  Previous studies have successfully identified the genetic diversity of the MC4R associated with growth traits.  However, studies on Bali cattle are limited.  This study aimed to identify the SNP markers of the MC4R gene and its effect on birth body weight, weaning body weight, weaning chest girth, weaning withers height, weaning body length, yearling body weight, yearling chest girth, yearling withers height, and yearling body length in Bali cattle (n=43).  The MC4R genotype was identified by sequencing and aligned using BioEdit v.7.2.5.  The association between genotype and growth traits was analyzed using the GLM procedure and DMRT in RStudio program v.2022.02. Four SNPs were identified in the exon region:  g.355G>T, g.394C>T, g.463G>A, and g.682G>A.  Based on the Chi-square test, the population was fitted with HWE (p>0.05).  Genotype-phenotype association based on SNPs showed no significant result (p>0.05) where the g.682G>A (AG) locus had values of WB (104.33+17.15 kg), WCG (112.83+3.66 kg), WBL (89.50+3.94 kg), YB (124.17+22.44 kg), YCG (120.50+5.50 kg), and YBL (92.83+4.31 kg) higher than the other genotypes.  Association based on haplotype type showed significant results (p<0.05) in BB, where haplotype 2 had the highest BB (21.17+0.75 kg).  In conclusion, the SNP markers found in this study were polymorphic but did not affect growth traits in Bali cattle.

Bali Cattle; Genetic Diversity; Growth Traits; MC4R Gene; Single Nucleotide Polymorphism

Al-Mamun HA, Clark SA, Kwan P, Gondro C. 2015. Genome‑wide linkage disequilibrium and genetic diversity in five populations of Australian domestic sheep. Genet Sel Evol. 47:1–14. DOI:10.1186/s12711-015-0169-6.

Al-sharif MM, Radwan HA, Hendam BM, Ateya AI. 2022. Exploring single nucleotide polymorphisms in GH, IGF-I, MC4R, and DGAT1 genes as predictors for growth performance in dromedary camel using multiple linear regression analysis. Small Rumin Res. 207:1–9. DOI:10.1016/j.smallrumres.2022.106619.

Alwiyah, Nuraini H, Agung PP, Jakaria J. 2016. Polymorphism stearoyl-coa desaturase (SCD) gene and association with characteristics of meat in Bali cattle. J Indones Trop Anim Agric. 41:188–195. DOI:10.14710/jitaa.41.4.188-195.

Ayers KL, Glicksberg BS, Garfield AS, Longerich S, White JA, Yang P, Du L, Chittenden TW, Gulcher JR, Roy S, et al. 2018. Melanocortin 4 receptor pathway dysfunction in obesity: Patient stratification aimed at MC4R agonist treatment. J Clin Endocrinol Metab. 103:2601–2612. DOI:10.1210/jc.2018-00258.

Bali S, Robinson BR, Sathuvalli V, Bamberg J, Goyer A. 2018. Single Nucleotide Polymorphism (SNP) markers associated with high folate content in wild potato species. PLoS One. 13:1–17. DOI:10.1371/journal.pone.0193415.

Botstein D, White RL, Skolnick M, Davis RW. 1980. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 32:314–331.

Dairoh, Jakaria, Ulum M, Sumantri C. 2021. Association of SNP g.232 G>T calpain gene with growth and live meat quality prediction using ultrasound images in Bali cattle. J Ilmu Ternak dan Vet. 26:49–56. DOI:10.14334 /jitv.v26i2.2701.

Du X, Chen C, Yuan Z, Zhang L, Chen X, Wang Y, Gao X, Zhang L, Gao H, Li J, Xu S. 2013. Genetic polymorphisms of MC4R and IGF2 gene association with feed conversion efficiency traits in beef cattle. Pak Vet J. 33:418–422.

Fahira A, Noor R, Jakaria. 2022. Diversity of SNP c .795A>G PLAG1 gene and its association to birth weight of Bali cattle. J Ilmu Ternak dan Vet. 27:107–113. DOI:10. 14334/jitv.v27i3.3045.

Fathoni A, Sumadi S, Budisatria IGS, Sari APZNL, Maharani D. 2020. Association between the melanocortinâ€4 receptor (MC4R) gene polymorphisms and growth trait in Sumba Ongole cattle. Iran J Appl Anim Sci. 10:603–609.

Hafid H, Hasnudi, Bain HA, Naisu F, Inderawati, Patriani P, Ananda SH. 2019. Effect of fasting time before slaughtering on body weight loss and carcass percentage of Bali cattle. In: Int Conf Agric Environ Food Secur 2018. Medan: IOP Publishing. p.1–7. DOI:10.1088 /1755-1315/260/1/012051.

Hao H, Lin R, Li Z, Shi W, Huang T, Niu J, Han J, Li Q. 2019. MC4R deficiency in pigs results in hyperphagia and, ultimately, hepatic steatosis without a high-fat diet. Biochem Biophys Res Commun. 520:651–656. DOI:10.1016/j.bbrc.2019.08.016.

Jakaria J, Ladhunka Nur Aliyya W, Ismail R, Yuni Siswanti S, Fakhrul Ulum M, Priyanto R. 2021. Discovery of SNPs and indel 11-bp of the myostatin gene and its association with the double-muscled phenotype in Belgian blue crossbred cattle. Gene. 784:1–7. DOI:10. 1016/j.gene.2021.145598.

Ju SH, Cho G, Sohn J. 2018. Understanding melanocortin-4 receptor control of neuronal circuits : Toward novel therapeutics for obesity syndrome. Pharmacol Res. 129:10–19. DOI:10.1016/j.phrs.2018.01.004.

Karimah SN, Noor RR, Jakaria J. 2021. Identification of SNP g.10428C>T of stearoyl-coa desaturase gene related to meat quality in Bali cattle using PCR-RFLP method. J Indones Trop Anim Agric. 46:295–303. DOI:10.14710 /jitaa.46.4.295-303.

Kaswati, Sumadi, Ngadiyono N. 2013. Estimasi nilai heritabilitas berat lahir, sapih, dan umur satu tahun pada sapi Bali di Balai Pembibitan Ternak Unggul sapi Bali. Bul Peternak. 37:74–78.

Kühnen P, Krude H, Biebermann H. 2018. Melanocortin-4 receptor signaling : importance for weight regulation and obesity treatment. Trends Mol Med. 25:136–148. DOI:10.1016/j.molmed.2018.12.002.

Lachance J. 2016. Hardy-Weinberg equilibrium and random mating. Encycl Evol Biol. 2:208–211. DOI:10.10 16/B978-0-12-800049-6.00022-6.

Lee Y, Park S, Kim H, Lee SK, Kim JW, Lee HK, Jeong DK, Lee SJ. 2013. A C1069G SNP of the MC4R gene and its association with economic traits in Korean native cattle (brown, brindle, and black). Electron J Biotechnol. 16:1–5. DOI:10.2225/vol16-issue5-fulltext-5.

Liu GY, Raza SHA, Zhou L, El-Aziz AHA, Sabek A, Shoorei H, Amjadi M, Gui L sheng. 2020. The genetic polymorphisms of the melanocortin-4 receptor gene are associated with carcass quality traits in a Chinese indigenous beef cattle breed. Res Vet Sci. 132:202–206. DOI:10.1016/j.rvsc.2020.06.011.

Melka MG, Stachowicz K, Miglior F, Schenkel FS. 2013. Analyzes of genetic diversity in five Canadian dairy breeds using pedigree data. J Anim Breed Genet. 130:476–486. DOI:10.1111/jbg.12050.

Mohamad K, Olsson M, Andersson G, Purwantara B, Tol HTA Van, Colenbrander B. 2012. The origin of Indonesian cattle and conservation genetics of the Bali cattle breed. Reprod Domest Anim. 47:18–20. DOI:10.1111/j.1439-0531.2011.01960.x.

Nei M, Kumar S. 2000. Molecular Evolution and Phylogenetics. New York (USA): Oxford University Pr.

Perdana YC, Hartatik T. 2022. Restriction mapping of MC4R gene on Bali cattle (Bos sondaicus) as a genetic marker for a breeding program in compared to Bos taurus and Bos indicus. J Trop Biodivers Biotechnol. 07:1–8. DOI:10.22146/jtbb.67636.

Pratiwi N, Maskur, Priyanto R, Jakaria J. 2016. Novel SNP of calpain-1 (CAPN1) gene and its association with carcass and meat characteristics traits in Bali cattle. J Indones Trop Anim Agric. 41:109–116. DOI:10.14710/jitaa. 41.3.109-116.

Putra IGR, Sari DA, Rachmawati SM, Oktaviani R, Noor RR, Jakaria J. 2021. Identification of single nucleotide polymorphism c.957A>C of PLAG1 gene and its association with growth traits in Bali cattle. J Indones Trop Anim Agric. 46:199–208. DOI:10.14710/jitaa. 46.3.199-208.

Saini BL, Gaur GK, Sahoo NR, Mendiratta SK, Kumar A, Naha BC, Baranwal A, Yadav V, Jaiswal RK. 2018. Polymorphism distribution of RYR1, PRKAG3, HFABP, MYF-5, and MC4R genes in crossbred pigs. Mol Biol Rep. 45:1575–1585. DOI:10.1007/s11033-018-4263-z.

Saputra EA, Ulum MF, Jakaria. 2020. Association of SNP g.643G>A of MYF5 gene polymorphism with body weight and body measurements in Bali cattle. 45:1–6. DOI:10.14710/jitaa.45.1.1-6.

Seong J, Suh DS, Park K Do, Lee HK, Kong HS. 2012. Identification and analysis of MC4R polymorphisms and their association with economic traits of Korean cattle (Hanwoo). Mol Biol Rep. 39:3597–3601. DOI:10. 1007/s11033-011-1133-3.

Shan H, Song X, Cao Y, Xiong P, Wu J, Jiang J, Jiang Y. 2020. Association of the melanocortin 4 receptor (MC4R) gene polymorphism with growth traits of Hu sheep. Small Rumin Res. 192:1–7. DOI:10.1016/j.smallrumres. 2020.106206.

Shishay G, Liu G, Jiang X, Yu Y, Teketay W, Du D, Jing H, Liu C. 2019. Variation in the promoter region of the MC4R gene elucidates the association of body measurement traits in Hu sheep. Internaotioanl J Mol Sci. 20:1–18. DOI:10.3390/ijms20020240.

Singh U, Deb R, Alyethodi RR, Alex R, Kumar S, Chakraborty S, Dhama K, Sharma A. 2014. Molecular markers and their applications in cattle genetic research: A review. Biomarkers Genomic Med. 6:49–58. DOI:10.1016 /j.bgm.2014.03.001.

Sulistiyoningtiyas I, Nurgiartiningsih VMA, Ciptadi G. 2017. Evaluasi performa bobot badan dan statistik vital sapi Madura berdasarkan tahun kelahiran. J Ilm Peternak Terpadu. 5:40–43. DOI:10.23960/jipt.v5i2.p.40-43.

Teixeira JC, Huber CD. 2021. The inflated significance of neutral genetic diversity in conservation genetics. 118:1–10. DOI:10.1073/pnas.2015096118.

Utomo B, Rimayanti, Triana IN, Fadholly A. 2021. Melanocortin-4 receptor and leptin as genes for the selection of superior Madrasin cattle. Vet World. 14:3224–3228. DOI:10.1088/1755-1315/803/1/012004.

Volkandari SD, Hartatik T, Sumadi. 2013. Polimorfisme Gen Growth Hormone (GH) pada Sapi Limura. Bul Peternak. 37:67–73. DOI:10.21059/buletinpete rnak.v37i2.2423.

Wawo AA. 2018. Effect of bulls on birth rate and birth weight by using semi-intensive Bali cattle maintenance. Chalaza J Anim Husb. 3:24–28. DOI:10.31327/chalaza.v3i1.539.

You P, Hu H, Chen Y, Zhao Y, Yang Y, Wang T, Xing R, Shao Y, Zhang W, Li D, et al. 2016. Effects of

melanocortin 3 and 4 receptor deficiency on energy homeostasis in rats. Sci Rep. 6:1–12. DOI:10. 1038/srep34938.

Zhao C, Raza SHA, Khan R, Sabek A, Khan S, Ullah I, Memon S, El-Aziz AHA, Shah MA, Shijun L, et al. 2020. Genetic variants in MYF5 affected growth traits and beef quality traits in Chinese Qinchuan cattle. Genomics. 112:2804–2812. DOI:10.1016/j.ygeno.2020.03.018.