GENETIC VARIATION OF cDNA OF LDLR GENE IN HYPORESPONDER CYNOMOLGUS MACAQUES (Macaca fascicularis)

Achmad Taher, Dedy Duryadi Solihin, Sulistiyani Sulistiyani, Dondin Sajuthi, Dewi Apri Astuti

Abstract


The study aimed to identify genetic variation of cDNA sequence from low density lipoprotein receptor (LDLR) gene of hyporesponder cynomolgus macaques. The animal used in this study was one hyporesponder cynomolgus macaque obtained from selection result in Primate Research Center-Bogor Institute of Agriculture (PSSP IPB). Amplification of cDNA from LDLR gene was performed using polymerase chain reaction (PCR) method with 4 pairs of walking primer. Alignment of amplification result sequence from 4 pairs of walking primer generated target sequence of 2353 bp which located on position 188-2540. Analysis of target sequence alignment on reference sequence in GenBank found 8 single nucleotide polymorphism (SNP), namely c408C>T; c.1200C>T; c.1497C>T; c.1644T>C; 1791T>C; 1804A>G; 2088C>T; and 2377G>A. Of 8 SNPs, c.1804A>G and 2377G>A. Two SNP (c.1804A>G; dan 2377G>A) caused changing of amino acids composition namely p.K602E (lysine → glutamate) and p.V793I (valine → isoleucine). This result proved the potential use of genetic variation of cDNA sequence from LDLR gene as genetic marker for selection of hyporesponder cynomolgus macaques.

Keywords


hyporesponder; LDLR; Macaca fascicularis; SNP

References


Astuti, D.A., D. Sajuthi, I.H. Suparto, J. Kaplan, S. Appt, T.B.Clarkson. 2014. The development of diets to induce atherogenic lipid profiles for cynomolgus monkeys in their country of origin. WJAR. 2 (5): 247-251.

Beynen, A.C., M.B. Katan, Van Zutphen. 1987. Hypo- and hyperresponder: individual differences in response of serum cholesterol concentration to change in diet. Adv Lipid Res. 22:115-71.

Blancher. A., A. Aarnink, K. Tanaka, M. Ota, H. Inoko, et al. 2012. Study of cynomolgus monkey (Macaca fascicularis) Mhc DRB gene polymorphisms in four population. Immunogenetics. 62:123-136.

Brown, M.S. and J.L. Goldstein. 1986. A receptor-mediated pathway for cholesterol homeostasis. Science. 232: 34-47.

Clarkson, T.B., N.J. Alexander, T.M. Morgan. 1988. Atherosclerosis of cynomolgus monkey hyper and hyporesponsive to dietary cholesterol. Arterioscler Thromb Vasc Biol. 8(5):488-498.

Ebeling, M., E. Kung, A. See, C. Broger, G. Steiner, M. Berrera M, et al. 2011. Genome-based analysis of nonhuman primate Macaca fascicularis as a model for drug safety assessment. Genome Research. 21:1746-1756.

Flynn S, Satkoski J, Lerche N, Kanthaswamy S, Smith DG. 2009. Genetic variation at the TNF-α promoter and malaria susceptibility in rhesus (Macaca mulatta) and long-tailed (Macaca fascicularis) macaques. Infection, Genetic and Evolution. 9:769-777.

Franceschini M., H. Muallem, K.M. Rose, Boewinkle, N. Maeda. 2009. LDL receptor polymorphisms and risk coronary heart disease: the atherosclerosis risk in communities study. J Thromb Homeost. 3:496-498.

Haus T., B. Fergusson, J. Rogers, G. Doxiadis, U. Certa, N.J. Rose, R. Teepe, G.F. Weinbauer, C. Roos. 2014. Genotyping of nonhuman primate models: implications for biomedical research. Trends in Genetics. 30(11):482-487.

Higashino A, Sakate R, Kameoka Y, Takahashi I, Hirata M, Tanuma R, Masui T, Yasutomi Y, Osada N. 2012. Whole-genome sequencing and analysis of the malaysian cynomolgus macaque (Macaca fascicularis) genome. Genome Biology. 13:R58

Hobbs, H.H., D.W. Russell, M.S. Brown, Goldstain. 1990. The receptor LDL locu in familial hypercholesterolemia: mutation analysis of a membran protein. Annu Rev Genet. 24: 133-170.

Hummel, M., Z. Li, D. Pfaffinger, L. Neven, M. Scanu. 1990. Familial hypercholesterolemia in a rhesus monkey pedigree: molecular basis of LDL receptor deficiency. Proc. Natl. Acad. Sci. USA. 87:3122-3126.

Linsel-Nitschke, P., A. Gotz, Erdmann, I. Braenne, P. Braund, C. Hengstenberg, K. Stark, M. Fischer, S. Schreiber, El Mokhtari, et al. 2008. Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease-A mendelian randomisation study. Plos ONE. 3(8):e2986.

Long X.J., R.X. Yin, K.L. Li, W.Y. Liu, L. Zhang, X.L. Cao, et al. 2011. Low density lipoprotein receptor gene ava II polymorphism and serum lipid levels in the guangxi bai ku yao and hand populations. Lipid in health and disease. 34:1-12.

Kathiresan, S., O. Melander, D. Anevski, C. Guiducci, N.P. Burtt. 2008. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 358: 1240–1249.

Masson, L.F., McNeill, Avenell. 2003. Genetic variation and the lipid response to dietary intervention: a systematic review. Am J Clin Nutr.77(5):1098-1111.

Putra, I.G.A. 2009. Polimorfisme gen penyandi karakter obesitas (MCR4/reseptor melanokortin 4) pada monyet ekor panjang (Macaca fascicularis) asal bali, jawa timur dan Sumatra. Disertasi. Sekolah Pascasarjana Institut Pertanian Bogor. Bogor

Rogers, J. 2013. In transition: primate genomics at a time of rapid change. ILAR J. 54: 224–233.

Sajuthi, D., J. Pamungkas, D. Iskandriati. 2015. Overview of the use of Indonesia nonhuman primates for biomedical research in Indonesia. Abstract International Seminar: Nonhuman Primate in Biology, Conservation and Biomedical Research, Bogor August 31.

Sandhu, M., D.M. Waterworth, S.L. Debenham, W. Wheeler, K. Papadakis, et al. 2008. LDL-cholesterol concentrations: a genome-wide association study. Lancet. 371: 483–491.

Street, S.L., R.C. Kyes, R. Grant, B. Fergusson. 2007. Single nucleotide polymorphisms (SNPs) are highly conserved in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. BMC Genomic. 8. doi:10.1186/147-2164-8-480.

Sudhof, T.C., J.L. Goldstein, M.S. Brown, D.W. Russell. 1985. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 228: 815-22.

Talmud, P.J., S. Shah, R. Whittall, M. Futema, P. Howard, J.A. Cooper, S.C. Harrison, K. Li, F. Drenos, F. Karpe, et al. 2013. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia, a case–control study. Lancet. 381:1293–1301.

Tamura K., G. Stecher, D. Peterson, A. Filipski A, S. Kumar S. 2013. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 30: 2725-2729.

Turley, S.D., D.K. Spady, J.M. Dietschy. 1997. Identification of a metabolic difference accounting for the hyper- and hyporesponder phenotypes of chynomolgus monkey. Journal of Lipid Reseach. 38(8):1590-1611.

Uno. Y., F. Martinon, G. Moine, Le Grand, et al. 2010. Genetic variant of CY3A4 and CYP3A5 in cynomolgus and rhesus macaques. Drug Metabolism and Disposition. 38:209-216.

Willer, C.J., S. Sanna, A.U. Jackson, A. Scuteri, L.L. Bonnycastle. 2008. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 40 : 161 – 169.

Wu, H. and K. Adkins. 2012. Identification of polymorphisms in genes of the immune system in cynomolgus macaques. Mamm Genome. 23:467-477.




DOI: https://doi.org/10.21157/j.ked.hewan.v11i3.2939

Refbacks

  • There are currently no refbacks.


Copyright (c) 2020 by author and J. Kedokt. Hewan

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

Indexed by:

          
  

p-ISSN: 1978-225X e-ISSN: 2502-5600 Copyright© 2007-2020