Melanocortin-4 Receptor (MC4R) Gene as the Main Gene for Rapid Growth Selection in Beef Cattle

Peni Wahyu Prihandini, D Maharani

Abstract

Genetic improvement for economic traits such as growth is important in beef cattle selection program. This paper discusses melanocortin-4 receptor (MC4R) gene as a candidate gene for rapid growth based on its function, location and pathway, as well as its polymorphism and identified genotypes associated with economic traits, and its application as a marker-assisted selection. MC4R is a prominent gene encoding growth traits and has a critical role in mediating the effect of leptin in regulating food consumption and energy balance. Many identified MC4R gene polymorphisms are associated with growth traits. The MC4R gene, therefore, is considered as a functional candidate gene for growth traits and can be used as a marker in selection program based on molecular genetics. The use of molecular markers such as MC4R gene, therefore, can be applied in genetic improvement program for growth traits in cattle. By using MC4R gene, the efforts to build breeding system in small populations can be proposed. For instance, with an effective population size (Ne) of about 40 heads, the first generation (G1) will be obtained with a composition of GG 61.1%, CG 33.3% and CC 5.6% and male and female ratio of 178:11 and generates ideal Ne of 41 heads. In the third generation, therefore, GG composition will be 100%. The results of molecular analysis can be further used as a guideline in the development and genetic improvement strategies of beef cattle.

Keywords

MC4R gene; weaning weight; Bos javanicus; beef cattle; selection

Full Text:

PDF

References

Alfieri A, Pasanisi F, Salzano S, Esposito L, Martone D, Tafuri D, Daniele A, Contaldo F, Sacchetti L, Zagari A, Buono P. 2010. Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy. Gene. 457:35-41.

Amie-Marini AB, Aslinda K, Mohd-Hifzan R, Muhd-Faisal AB, Musaddin K. 2012. HaeIII-RFLP polymorphism of growth hormone gene in Savanna and Kalahari goats. Malays J Anim Sci. 15:13-19.

Al-Muhsen FA, Al-Nassir HS, Mirza S, Mnati AA. 2018. Association of growth hormone gene polymorphism with birth and weaning weight of Nuimi and Awassi sheep at Kerbala province. J Biochem Tech. 9:27-30.

Barton NH, Briggs DEG, Eisen JA, Goldstein DB, Patel NH. 2007. Evolution. 1st ed. New York (USA): Cold Spring Harbor Laboratory Press.

Benoit S, Schwartz M, Baskin D, Woods SC, Seeley RJ. 2000. CNS melanocortin system involvement in the regulation of food intake. Horm Behav. 37:299-305.

Butler AA. 2006. The melanocortin system and energy balance. Peptides. 27:281-290.

Chung ER, Kim WT. 2005. Association of SNP marker in IGF-Iand MYF5candidate genes with growth traits in Korean cattle. Asian-Aust J Anim Sci. 18:1061-1065.

De la Rosa Reyna XF, Montoya HM, Castrellón VV, Rincón AMS, Bracamonte MP, Ver WA. 2010. Polymorphisms in the IGF1 gene and their effect on growth traits in Mexican beef cattle. Genet Mol Res. 9:875-883.

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. J Pak Vet. 33:418-422.

Dubern B. 2015. MC4R and MC3R mutations. In: Frelut ML, editor. The ECOG’s eBook on child and adolescent obesity. Available on ebook. ecog-obesity. eu 2-7.

Eenennaam AV. 2009. Basics of DNA markers and genotyping. California (USA): Department of Animal Science, University of California.

Elrod S, Stansfield W. 2002. Genetika. Diterjemahkan oleh Wulandari DT. Jakarta (Indonesia): Erlangga. hlm. 33-41.

Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O'rahilly S. 2003. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. New England J Med. 348:1085-1095.

Fathoni A. 2016. Estimasi parameter genetik sifat pertumbuhan dan identifikasi gen MC4R sapi Peranakan Ongole di Kabupaten Kebumen Jawa Tengah [Tesis]. [Yogyakarta (Indonesia)]: Universitas Gadjah Mada.

Futuyma DJ. 2013. Evolution. 3rd ed. Massachusetts (USA): Sinauer Associates.

Gill JL, Bishop SC, McCorquodale C, Williams JL, Wiener P. 2010. Associations between single nucleotide polymorphisms in multiple candidate genes and carcass and meat quality traits in a commercial Angus-cross population. Meat Sci. 86: 985-993.

Grisart B, Coppieters W, Farnir F, Karim L, Ford C, Berzi P, Cambisano N, Mni M, Reid S, Simon P, Spelman R, Georges M, Snell R. 2002. Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition. Genome Res. 12: 222-231.

Guyton AC, Hall JE. 2006. Textbook of medical physiology. 11th ed. Philadelphia (USA): Elsevier Saunders. p. 871-875.

Haegeman AF, Coopman K, Jacobs M, Mattheeuws A, Van Zeveren L, Peelman. 2001. Bovine melanocortin receptor 4:cDNA sequence, polymorphisms and mapping. J Anim Genet. 32:189-192.

Haskell-Luevano C, Monck EK. 2001. Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor. Regul Pept. 99:1-7.

Horn F, Bettler E, Oliveira L, Campagne F, Cohen FE, Vriend G. 2003. GPCRDB informative system for G protein-coupled receptors. Nucleid Acids Res. 31:294-297.

Hernández N, Martínez-González JC, Parra-Bracamonte GM, Sifuentes-Rincón AM, López-Villalobos N, Morris ST, Briones-Encinia F, Ortega-Rivas E, Pacheco-Contreras VI, Meza-García LA. 2016. Association of polymorphisms in growth hormone and leptin candidate genes with live weight traits of Brahman cattle. Genet Mol Res. 15:gmr.15038449.

Hill WG. 1979. A note effective population size with overlapping generations. Genetics. 92:317-322

Hradecka E, Čitek J, Panicke L, Řehout V, Hanusova L. 2008. The relation of GH1, GHR and DGAT1 polymorphisms with estimated breeding values for milk production traits of German Holstein sires. Czech J Anim Sci. 53:238-245.

Huang M, Gao X, Li JY, Ren HY, Chen JB, Xu SZ. 2010. Polymorphisms in MC4R gene and correlations with economic traits in cattle. J Mol Biol Rep. 37:3941-3944.

Huszar D, Lynch CA, Huntress FV, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F. 1997. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 88:131-141.

Kuehn LA, Rohrer GA, Nonneman DJ, Thallman RM, Leymaster KA. 2007. Detection of single nucleotide polymorphisms associated with ultrasonic backfat depth in segregating Meishan x White Composite population. J Anim Sci. 85:1111-1119.

Lacorte GA, Machado MA, Martinez ML, Campos AL, Maciel RP, Verneque RS, Teodoro RL, Peixoto MGCD, Carvalho MRS, Fonseca CG. 2006. DGAT1 K232A polymorphism in Brazilian cattle breeds. Genet Mol Res. 5:475-482.

Lee Y, Park S, Kim H, Lee SK, Kim JW, Lee HK, 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.

Li H, Deeb N, Zhou H, Mitchell AD, Ashwell CM, Lamont SJ. 2003. Chicken quantitative trait loci for growth and body composition associated with transforming growth factor-β genes. Poult Sci. 82:347-356.

Liu H, Tian W, Zan L, Wang H, Cui H. 2010. Mutation of MC4R gene and its association with economic traits in Qinchuan cattle. Mol Biol Rep. 37:535-540.

Lubrano-Berthelier C, Cavazos M, Duben B, Shapiro A, Stunff CL, Zhang S, Picart F, Govaerts C, Froguel P, Bougnères P, Clement K, Vaisse C. 2003. Molecular genetics of human obesity-associated MC4R mutations. Ann NY Acad Sci. 994:49-57.

MacKenzie RG. 2006. Obesity-associated mutations in the human melanocortin-4 receptor gene. Peptides. 27:395-403.

Maharani D, Fathoni A, Sumadi, Hartatik T, Khusnudin M. 2018. Identification of MC4R gene and its association with body weigh and body size in Kebumen Ongole grade cattle. J Ind Tropic Anim Agric. 43:87-93.

Malewa AD, Hakim L, Maylinda S, Husain MH. 2014. Growth hormone gene polymorphisms of Indonesia fat tailed sheep using PCR-RFLP and their relationship with growth traits. Livest Res Rural Develop. 26:115. Available from: http://www.lrrd.org/lrrd26/6/male26115.htm

McLean KL, Schmutz SM. 2011. Melanocortin 4 receptor polymorphism is associated with carcass fat in beef cattle. Can J Anim Sci. 91:75–79.

Nielsen R, Slatkin M. 2013. An introduction to population genetics: Theory and applications. London (UK): Macmillan Education.

Pal A, Chakravarty AK, Bhattacharya TK, Joshi BK, Sharma A. 2004. Detection of polymorphism of growth hormone gene for the analysis of relationship between allele type and growth traits in Karan Fries cattle. Asian-Aust J Anim Sci. 17:1334-1337.

Prihandini PW. 2018. Analisis potensi genetik sapi Madura di Kabupaten Pamekasan dan Loka Penelitian Sapi Potong Jawa Timur [Disertasi]. [Yogyakarta (Indonesia)]: Universitas Gadjah Mada.

Prihandini PW, Sumadi, Suparta G, Maharani D. 2019. Melanocortin-4 Receptor (MC4R) gene polymorphism and itseffect on growth traits in Madura cattle. J Indones Trop Anim Agric.

:38-46.

Putra WPB, Indriastuti R. 2017. Gen leptin sebagai gen potensial untuk seleksi molekuler pada sapi di Indonesia. Wartazoa. 3:105-116.

Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, Perusse L, Bouchard C. 2006. The human obesity gene map: the 2005 update. J Obesity. 14:529-644.

Rosmond R, Chagnon M, Bouchard C, Bjorntorp P. 2001. A missense mutation in the human melanocortin-4 receptor gene in relation to abdominal obesity and salivary cortisol. Diabetologia. 44:1335-1338.

Roth CL, Ludwig M, Woelfle J, Fan ZC, Brumm H, Biebermann H, Tao YX. 2009. A novel melanocortin-4 receptor gene mutation in a female patient with severe childhood obesity. Endocrine. 36:52-59.

Seeley RJ, Yagaloff KA, Fisher SL, Burn P, Thiele TE, van Dijk G, Baskin DG, Schwartz MW. 1997. Melanocortin receptors in leptin effects. Nature. 390:349.

Seong J, Lee HK, Suh DS, Kong HS, Park HD. 2012. Identiï¬cation and analysis of MC4R polymorphisms and their association with economic traits of korean cattle (Hanwoo). Mol Biol Rep. 5:3597-3601.

Supakorn C, Mekchay S, Siripholvat V, Sopannarath P, Koonawootrittriron S, Tumwasorn S. 2007. Effect of genetic polymorphism of bovine growth hormone gene on preweaning growth traits in a Thai multibreed beef population. Kasetsart J Nat Sci. 41:484-492.

Tao YA. 2005. Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity. Mol Cell Endocrinol. 239:1-14.

Thue TD, Schmutz SM, Buchanan FC. 2001. A SNP in the cattle MC4R gene is used to map MC4R to BTA 24. Anim Genet. 32:390-391.

Tizioto PC, Meirelles SL, Tulio RR, Rosa AN, Alencar MM, Medeiros SR, Siqueira F, Feijó GLD, Silva LOC, Torres Junior RAA, Regitano LCA. 2012. Candidate genes for production traits in Nelore beef cattle. Genet Mol Res. 11:4138-4414.

Valle E, Habermann FA, Moore SS, Crews DH, Benkel BF. 2004. Genomic localization and SNP discovery in the bovine melanocortin receptor 4 gene (MC4R). Anim Genet. 35:351-352.

Yeo GSH, Farooqi S, Aminian S, Halsall DJ, Stanhope RG, O’Rahilly S. 1998. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet. 20:111-112.

Zhang CL, Chen H, Wang YH, Lan XY, Zhang L, Zhang AL, Zhang RF. 2006. Association of a missense mutation of The MC4R gene with growth traits in cattle (brief report). Archiv Fur Tierzucht. 49:515-516.

Zhang CL, Wang YH, Chen H, Lan XY, Lei CZ, Fang XT. 2009. Association between variants in the 50-untranslated region of the bovine MC4R gene and two growth traits in Nanyang cattle. Mol Biol Rep. 36:1839-1843.

 DOI  https://doi.org/10.14334/wartazoa.v29i2.1955

Refbacks

  • There are currently no refbacks.

Copyright (c)  2019 WARTAZOA. Indonesian Bulletin of Animal and Veterinary Sciences

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

View My Stats

Bookmark and Share