Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-24T02:48:04.688Z Has data issue: false hasContentIssue false
  • English
  • Français

The Hepatocyte nuclear factor-1 alpha (HNF1A) gene is associated with fatness and loin muscle area in the pig

Published online by Cambridge University Press:  14 May 2010

B. Fan ,
Z.-Q. Du  and
M. F. Rothschild
B. Fan
Affiliation:
Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University, Ames, IA 50011, USA Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education and College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China
Z.-Q. Du
Affiliation:
Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University, Ames, IA 50011, USA
M. F. Rothschild*
Affiliation:
Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University, Ames, IA 50011, USA
*
†E-mail: mfrothsc@iastate.edu
Get access

Abstract

The significance of hepatocyte nuclear factors (HNFs) in β-cell development and function has been generally recognized in humans, as evidenced by their associations with cases of maturity onset diabetes of the young (MODY). Common Hepatocyte nuclear factor-1 alpha (HNF1A), Hepatocyte nuclear factor-1 beta (HNF1B) and Hepatocyte nuclear factor-4 alpha (HNF4A) mutations could lead to monogenic forms 3, 5 and 1 of diabetes mellitus, respectively, and were characterized by MODY in humans. In this study, multiple variants were discovered in the porcine HNF1A and HNF4A genes, and one single-nucleotide polymorphism (SNP) was detected in the HNF1B gene. Using the Iowa State University Berkshire × Yorkshire pig resource population, the HNF1A, HNF1B and HNF4A genes were mapped on chromosomes 14, 12 and 17, respectively. The linkage disequilibrium (LD) analyses indicated that most of the HNF1A variants were not in strong LD with each other; however, nearly all of them were highly significantly (P < 0.01) associated with loin muscle area (LMA). The SNPs c.327-19G>T and c.1768+40_23del were significantly (P < 0.05) associated with backfat and total lipid percentage, and the latter was also associated with muscle glycogen metabolism measures. Four major haplotypes were observed and the association analyses suggested that haplotype 3 (-CGCGD-, I indicates Insertion and D indicates Deletion) was favorable for reduced backfat, while haplotype 1 (-CACGI-) was unfavorably associated with backfat and LMA. There was no significant interaction effect on backfat among the SNPs c.327-19G>T, c.1768+40_23del of the HNF1A gene and c.646C>T of the transcription factor-7-like 2 (TCF7L2) gene. These findings suggest that the HNF1A gene has significant effects on both fatness- and meat production-related traits. No significant associations with production traits with the SNPs from the HNF1B and HNF4A genes were observed in the study.

Keywords

HNF1Afatnessloin muscle areaassociationpig
Type
Full Paper
Information
animal , Volume 4 , Issue 10 , October 2010 , pp. 1619 - 1627
Copyright
Copyright © The Animal Consortium 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Barrett, JE, Fry, B, Maller, J, Daly, MJ 2005. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265.CrossRefGoogle ScholarPubMed
Bellanné-Chantelot, C, Carette, C, Riveline, JP, Valéro, R, Gautier, JF, Larger, E, Reznik, Y, Ducluzeau, PH, Sola, A, Hartemann-Heurtier, A, Lecomte, P, Chaillous, L, Laloi-Michelin, M, Wilhem, JM, Cuny, P, Duron, F, Guerci, B, Jeandidier, N, Mosnier-Pudar, H, Assayag, M, Dubois-Laforgue, D, Velho, G, Timsit, J 2008. The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3. Diabetes 57, 503–509.CrossRefGoogle ScholarPubMed
Ciobanu, D, Bastiaansen, J, Malek, M, Helm, J, Woollard, J, Plastow, G, Rothschild, M 2001. Evidence for new alleles in the protein kinase adenosine monophosphate-activated gamma (3)-subunit gene associated with low glycogen content in pig skeletal muscle and improved meat quality. Genetics 159, 1151–1162.CrossRefGoogle Scholar
Costa, RH, Kalinichenko, VV, Holterman, AX, Wang, X 2003. Transcription factors in liver development, differentiation, and regeneration. Hepatology 38, 1331–1347.CrossRefGoogle ScholarPubMed
de Koning, DJ, Rattink, AP, Harlizius, B, Groenen, MAM, Brascamp, EW, van Arendonk, JAM 2001. Detection and characterization of quantitative trait loci for growth and reproduction traits in pigs. Livestock Production Science 72, 185–198.CrossRefGoogle Scholar
Dragos-Wendrich, M, Sternstein, I, Brunsch, C, Moser, G, Bartenschlager, H, Reiner, G, Geldermann, H 2003. Linkage and QTL mapping for Sus scrofa chromosome 14. Journal of Animal Breeding and Genetics 120, 111–118.CrossRefGoogle Scholar
Du, ZQ, Fan, B, Zhao, X, Amoako, R, Rothschild, MF 2009. Association analyses between type 2 diabetes genes and obesity traits in pigs. Obesity 17, 323–329.CrossRefGoogle ScholarPubMed
Ellard, S, Colclough, K 2006. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in muatruity-onset diabetes of the young. Human Mutation 27, 854–869.CrossRefGoogle ScholarPubMed
Fan, B, Du, ZQ, Rothschild, MF 2009. The fat mass and obesity-associated (FTO) gene is associated with intramuscular fat content and growth rate in the pig. Animal Biotechnology 20, 58–70.CrossRefGoogle ScholarPubMed
Fontanesi, L, Scotti, E, Buttazzoni, L, Davoli, R, Russo, V 2008. The porcine fat mass and obesity associated (FTO) gene is associated with fat deposition in Italian Duroc pigs. Animal Genetics 40, 90–93.CrossRefGoogle ScholarPubMed
Green, P, Falls, K, Crooks, S 1990. Documentation for CRIMAP, version 2.4. Washington University School of Medicine, St. Louis, MO, USA.Google Scholar
Harries, LW, Ellard, S, Stride, A, Morgan, HG, Hattersley, AT, The European MODY consortium 2006. Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Human Molecular Genetics 15, 2216–2224.CrossRefGoogle ScholarPubMed
Hart, EA, Caccamo, M, Harrow, JL, Humphray, SJ, Gilbert, JGR, Trevanion, S, Hubbard, T, Rogers, J, Rothschild, MF 2007. Lessons learned from the initial sequencing of the pig genome: comparative analysis of an 8 Mb region of pig chromosome 17. Genome Biology 8, R168.CrossRefGoogle ScholarPubMed
Hino, K, Tsuchiya, K, Fukao, T, Kiga, K, Okamoto, K, Kanai, T, Watanabe, M 2008. Inducible expression of microRNA-194 is regulated by HNF-1a during intestinal epithelial cell differentiation. RNA 14, 1433–1442.CrossRefGoogle Scholar
Horikawa, Y, Iwasaki, N, Hara, M, Furuta, H, Hinokio, Y, Cockburn, BN, Lindner, T, Yamagata, K, Ogata, M, Tomonaga, O, Kuroki, H, Kasahara, T, Iwamoto, Y, Bell, GI 1997. Mutation in hepatocyte nuclear factor-1 gene (TCF2) associated with MODY. Nature Genetics 17, 384–385.CrossRefGoogle ScholarPubMed
Kim, KS, Larsen, N, Short, T, Plastow, G, Rothschild, MF 2000. A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness, growth, and feed intake traits. Mammalian Genome 11, 131–135.CrossRefGoogle ScholarPubMed
Kim, KS, Thomsen, H, Bastiaansen, J, Nguyen, NT, Dekkers, JCM, Plastow, GS, Rothshild, MF 2004. Investigation of obesity candidate genes on porcine fat deposition quantitative trait loci regions. Obesity Research 12, 1981–1994.CrossRefGoogle ScholarPubMed
Kitanaka, S 2008. Role of HNF-1α and HNF-1β on insulin, IGF-1 and other potential target genes. Expert Review of Endocrinology and Metabolism 3, 441–452.CrossRefGoogle ScholarPubMed
Ktistaki, E, Talianidis, I 1997. Modulation of hepatic gene expression by hepatocyte nuclear factor 1. Science 277, 109–112.CrossRefGoogle ScholarPubMed
Lin, WY, Hu, YJ, Lee, YH 2008. Hepatocyte nuclear factor-1 regulates glucocorticoid receptor expression to control postnatal body growth. American Journal of Physiology – Gastrointestinal and Liver Physiology 295, G542–G551.CrossRefGoogle ScholarPubMed
Malek, M, Dekkers, JCM, Lee, HK, Baas, TJ, Rothschild, MF 2001a. A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. I. Growth and body composition. Mammalian Genome 12, 630–636.CrossRefGoogle ScholarPubMed
Malek, M, Dekkers, JCM, Lee, HK, Baas, TJ, Prusa, K, Huff-Lonergan, E, Rothschild, MF 2001b. A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. II. Meat and muscle composition. Mammalian Genome 12, 637–645.CrossRefGoogle ScholarPubMed
Paszek, AA, Wilkie, PJ, Flickinger, GH, Miller, LM, Louis, CF, Rohrer, GA, Alexander, LJ, Beattie, CW, Schook, LB 2001. Interval mapping of carcass and meat quality traits in a divergent swine cross. Animal Biotechnology 12, 155–165.CrossRefGoogle Scholar
Rhoads, DB, Levitsky, LL 2008. Function of HNF1 in the pathogenesis of diatetes. Expert Review of Endocrinology and Metabolism 3, 391–403.CrossRefGoogle Scholar
Rohrer, GA, Keele, JW 1998. Identification of quantitative trait loci affecting carcass composition inswine: I. Fat deposition traits. Journal of Animal Science 76, 2247–2254.CrossRefGoogle ScholarPubMed
Rowley, CW, Staloch, L, Divine, JK, McCaul, SP, Simon, TC 2006. Mechanisms of mutual functional interaction between HNF-4α and HNF-1α revealed by mutations that cause maturity onset diabetes of the young. American Journal of Physiology – Gastrointestinal and Liver Physiology 290, G466–G475.CrossRefGoogle ScholarPubMed
Ryffel, GU 2001. Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences. Journal of Molecular Endocrinology 27, 11–29.CrossRefGoogle ScholarPubMed
Seaton, G, Hernandez, J, Grunchec, JA, White, I, Allen, J, De Koning, DJ, Wei, W, Berry, D, Haley, C, Knott, S 2006. GridQTL: A Grid portal for QTL mapping of compute intensive datasets. Proceedings of the 8th World Congress on Genetics Applied to Livestock Production, August 13–18, 2006. Belo Horizonte, Brazil.Google Scholar
Shih, DQ, Bussen, M, Sehayek, E, Ananthanarayanan, M, Shneider, BL, Suchy, FJ, Shefer, S, Bollileni, JS, Gonzalez, FJ, Breslow, JL, Stoffel, M 2001. Hepatocyte nuclear factor-1 is an essential regulator of bile acid and plasma cholesterol metabolism. Nature Genetics 27, 375–382.CrossRefGoogle Scholar
Stephens, M, Smith, N, Donnelly, P 2001. A new statistical method for haplotype reconstruction from population data. The American Journal of Human Genetics 69, 978–989.CrossRefGoogle Scholar
Weedon, M, Frayling, TM 2007. Insights on pathogenesis of type 2 diabetes from MODY genetics. Current Diabetes Reports 7, 131–138.CrossRefGoogle ScholarPubMed
Wernersson, R, Schierup, MH, Jørgensen, FG, Gorodkin, J, Panitz, F, Staerfeldt, HH, Christensen, OF, Mailund, T, Hornshøj, H, Klein, A, Wang, J, Liu, B, Hu, S, Dong, W, Li, W, Wong, GK, Yu, J, Wang, J, Bendixen, C, Fredholm, M, Brunak, S, Yang, H, Bolund, L 2005. Pigs in sequence space: A 0.66 × coverage pig genome survey based on shotgun sequencing. BMC Genomics 6, 70.CrossRefGoogle Scholar
Winckler, W, Burtt, NP, Holmkvist, J, Cervin, C, de Bakker, PI, Sun, M, Almgren, P, Tuomi, T, Gaudet, D, Hudson, TJ, Ardlie, KG, Daly, MJ, Hirschhorn, JN, Altshuler, D, Groop, L 2005. Association of common variation in the HNF1A gene region with risk of type 2 diabetes. Diabetes 54, 2336–2342.CrossRefGoogle ScholarPubMed
Yamagata, K, Furuta, H, Oda, N, Kaisaki, PJ, Menzel, S, Cox, NJ, Fajans, SS, Signorini, S, Stoffel, M, Bell, GI 1996a. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature 384, 458–460.CrossRefGoogle ScholarPubMed
Yamagata, K, Oda, N, Kaisaki, PJ, Menzel, S, Furuta, H, Vaxillaire, M, Southam, L, Cox, RD, Lathrop, GM, Boriraj, VV, Chen, X, Cox, NJ, Oda, Y, Yano, H, Le Beau, MM, Yamada, S, Nishigori, H, Takeda, J, Fajans, SS, Hattersley, AT, Iwasaki, N, Hansen, T, Pedersen, O, Polonsky, KS, Bell, GI 1996b. Mutations in the hepatocyte nuclear factor-1 alpha gene in maturity-onset diabetes of the young (MODY3). Nature 384, 455–458.CrossRefGoogle ScholarPubMed