Abstract
In contrast to diseases caused by single-gene defects, many of the most common human maladies such as obesity, atherosclerosis, diabetes, and hypertension exhibit continuous phenotypic variation and a predominantly multifactorial and polygenic basis. Genes with roles in energy balance, nutrient partitioning, lipid and insulin metabolism, and a variety of behavioral traits are likely interacting with environmental stimuli to regulate obesity phenotypes. With the current proliferation of highly polymorphic genetic markers and the refinement of experimental approaches, it is now possible to screen thoroughly the genomes of model organisms for the individual genes or quantitative trait loci (QTL) that control measurable polygenic traits such as obesity. With the growing wealth of comparative mapping, it will be possible to predict the location of a homologous locus in the human after first mapping it in the mouse. Many experiments have been conducted in mice, rats, and pigs to estimate the number, location, and effect of QTL controlling obesity and related traits. This review describes the design and strategies of such studies and summarizes the results and their implications toward understanding the complex nature of obesity in humans.
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REFERENCES
Andersson, L., Archibald, A., Ashburner, M., Audun, S., Barendse, W., Bitgood, J., Bottema, C., Broad, T., Brown, S., Burt, D., Charlier, C., Copeland, N., Davis, S., Davisson, M., Edwards, J., Eggen, A., Elgar, G., Eppig, J. T., Franklin, I., Grewe, P., Gill, T., III, Graves, J. A. M., Hawken, R., Hetzel, J., Hilyard, A., Jacob, H., Jaswinska, L., Jenkins, N., Kunz, H., Levan, G., Lie, O., Lyons, L., Maccarone, P., Mellersh, C., Montgomery, G., Moore, S., Moran, C., Morizot, D., Neff, J., Nicholas, F., O'Brien, S., Parsons, Y., Peters, J., Postlethwait, J., Raymond, M., Rothschild, M., Schook, L., Sugimoto, Y., Szpirer, C., Tate, M., Taylor, J., VandeBerg, J., Wakefield, M., Wienberg, J., and Womack, J. (1996). Comparative genome organization of vertebrates. Mammal. Genome 7:717–734.
Andersson, L., Haley, C. S., Ellegren, H., Knott, S. A., Johansson, M., Andersson, K., Andersson-Eklund, L., Edfors-Lilja, I., Fredholm, M., Hansson, I., Häkansson, and Lundström (1994). Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science 263:1771–1774.
Astrup, A. (1993). Dietary composition, substrate balances and body fat in subjects with a predisposition to obesity. Int. J. Obesity 17(Suppl. 3):S32-S36.
Barendse, W., Vaiman, D., Kemp, S. J., Sugimoto, Y., Armitage, S., Williams, J. L., Sun, H. S., Eggen, A., Agaba, M., Aleyasin, S. A., Band, M., Bishop, M. D., Buitkamp, J., Byrne, K., Collins, F., Cooper, L., Coppettiers, W., Denys, B., Drinkwater, R. D., Easterday, K., Elduque, C., Ennis, S., Erhardt, G., Ferretti, L., Flavin, N., Gao, Q., Georges, M., Gurung, R., Harlizius, B., Hawkins, G., Hetzel, D. J. S., Hirano, T., Hulme, D., Joergensen, C., Kessler, M., Kirkpatrick, B. W., Konfortov, B., Kostia, S., Kuhn, C., Lenstra, J., Leveziel, H., Lewin, H. A., Leyhe, B., Li, L., Martin Buriel, I., McGraw, R. A., Miller, J. R., Moody, D. E., Moore, S. S., Nakane, S., Nijman, I., Olsaker, I., Pomp, D., Rando, A., Ron, M., Shalom, A., Soller, M., Tcale, A. J., Thieven, I., Urquhart, B., Vage, D-I., Van de Weghe, A., Varvio, S., Velmala, R., Vilkki, J., Weikard, R., Woodside, C., Womack, J. E., Zanotti, M., and Zaragoza, P. (1997). A medium density genetic linkage map of the bovine genome. Mammal. Genome 8:21–28.
Botstein, D., White, R. L., Skolnick, M., and Davis, R. W. (1980). Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32:314–331.
Bouchard, C., and Pérusse, L. (1996). Current status of the human obesity gene map. Obesity Res. 4:81–90.
Brenneman, R. A., Davis, S. K., Sanders, J. O., Burns, B. M., Wheeler, T. C., Turner, J. W., and Taylor, J. F. (1996). The polled locus maps to BTA1 in a Bos indicus by Bos taurus cross. J. Hered. 87:156–161.
Brockmann, G., Timtchenko, D., Das, P., Renne, U., Freyer, G., Kuhla, S., Teuscher, F., Wolf, J., Kühn, C., and Schwerin, M. (1996). Detection of QTL for body weight and body fat content in mice using genetic markers. J. Anim. Breed. Genet. 113:373–379.
Casas-Carrillo, E., Prill-Adams, A., Price, S. G., Clutter, A. C., and Kirkpatrick, B. W. (1997). Relationship of growth hormone and insulin-like growth factor-1 genotypes with growth and carcass traits in offspring of purebred and crossbred swine sires. Anim. Genet. (in press).
Cheverud, J. M., Routman, E. J., Duarte, F. A. M., von Swinderen, B., Cothran, K., and Perel, C. (1996). Quantitative trait loci for murine growth. Genetics 142:1305–1319.
Churchill, G. A., and Doerge, R. W. (1994). Empirical threshold values for quantitative trait mapping. Genetics 138:963–971.
Crabbe, J. C., Belknap, J. K., and Buck, K. J. (1994). Genetic animal models of alcohol and drug abuse. Science 264:1715–1723.
DeBry, R. W., and Seldin, M. F. (1996). Human/mouse homology relationships. Genomics 33:337–351.
Deng, A. Y., Dene, H., and Rapp, J. P. (1994). Mapping of a quantitative trait locus for blood pressure on rat chromosome 2. J. Clin. Invest. 94:431–436.
Dib, C., Faure, S., Fizames, C., Samson, D., Drouot, N., Vignal, A., Millasscau, P., Marc, S., Hazan, J., Scboun, E., Lathrop, M., Gyapay, G., Morissette, J., and Weissenbach, J. (1996). A comprehensive genetic-map of the human genome based on 5,264 microsatellites. Nature 380:152–154.
Dietrich, W. F., Miller, J., Steen, R., Merchant, M. A., Damronboles, D., Husain, Z., Dredge, R., Daly, M. J., Ingalls, K. A., Oconnor, T. J., Evans, C. A., Deangelis, M. M., Levinson, D. M., Kruglyak, L., Goodman, N., Copeland, N. G., Jenkins, N. A., Hawkins, T. L., Stein, L., Page, D. C., and Lander, E. S. (1996). A comprehensive genetic map of the mouse genome. Nature 380:149–152.
Dragani, T. A., Zeng, Z.-B., Canzlan, F., Gariboldi, M., Ghilarducci, M. T., Manenti, G., and Pierotti, M. A. (1995). Mapping of body weight loci on mouse Chromosome X. Mammal. Genome 6:778–781.
Eberhart, G. P., West, D. B., Boozer, C. N., and Atkinson, R. L. (1994). Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity. Am. J. Physiol. 266 (Regul. Integr. Comp. Physiol 35):R1423-R1428.
Eisen, E. J. (1986). Maturing patterns of organ weights in mice selected for rapid postweaning gain. Theor. Appl. Genet. 73:148–157.
Eisen, E. J. (1987). Selection for components related to body composition in mice: Direct responses. Theor. Appl. Genet. 74:793–801.
Eisen, E. J. (1989). Selection experiments for body composition in mice and rats: A review. Livestock Product. Sci. 23:17–32.
Eisen, E. J., and Leatherwood, J. M. (1978a). Adipose cellularity and body composition in polygenic obese mice as influenced by preweaning nutrition. J. Nutr. 108:1652–1662.
Eisen, E. J., and Leatherwood, J. M. (1978b). Effect of postweaning feed restriction on adipose cellularity and body composition in polygenic obese mice. J. Nutr. 108:1663–1672.
Festing, M. F. W. (1979a). Animal Models of Obesity, Oxford University Press, New York.
Festing, M. F. W. (1979b). The inheritance of obesity in animal models of obesity. In Festing, M. F. W. (ed.), Animal Models of Obesity, MacMillan Press, London, pp. 15–37.
Fitch, W. M., and Atchley, W. R. (1985). Evolution in inbred strains of mice appears rapid. Science 228:1169–1175.
Frankel, W. N. (1995). Taking stock of complex trait genetics in mice. Trends Genet. 11:471–476.
Gauguier, D., Froguel, P., Parent, V., Bernard, C., Bihoreau, M. T., Portha, B., James, M. R., Penicaud, L., Lathrop, M., and Ktorza, A. (1996). Chromosomal mapping of genetic-loci associated with non-insulin-dependent diabetes in the GK rat. Nature Genet. 12:38–43.
Goodale, H. (1938). A study of the inheritance of body weight in the albino mouse by selection. J. Hered. 29:101–112.
Haldane, J. B., Sprunt, A. D., and Haldane, N. M. (1915). Reduplication in mice. Science 5:133–135.
Haley, C. S. (1995). Livestock QTLs—Bringing home the bacon? Trends Genet. 11:488–492.
Haley, C. S., Knott, S. A., and Elsen, J. M. (1994). Mapping quantitative trait loci in crosses between outbred lines using least squares. Genetics 136:1195–1207.
Hanrahan, J. P., Eisen, E. J., and Legates, J. E. (1973). Effects of population size and selection intensity on short-term response to selection for postweaning gain in mice. Genetics 73:513–530.
Hilbert, P., Lindpainmer, K., Beckmann, J. S., Serikawa, T., Soubrier, F., Dubay, C., Cartwright, P., De Gouyon, B., Julier, C., Takahasi, S., Vincent, M., Ganten, D., Georges, M., and Lathrop, G. M. (1991). Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature 353:521–528.
Horvat, S., and Medrano, J. F. (1996a). Fine genetic-mapping of the region surrounding the high growth (hg) locus in mouse chromosome 10 targeting random amplified polymorphic DNA (RAPD) markers. Mammal. Genome 7:312–314.
Horvat, S., and Medrano, J. F. (1996b). The high growth (hg) locus maps to a deletion in mouse chromosome 10. Genontics 36:546–549.
Houpt, K. A., Houpt, T. R., and Pond, W. G. (1979). The pig as a model for the study of obesity and of the control of food intake: A review. Yale J. Biol. Med. 52:307.
Hyman, R. W., Frank, S., Warden, C. H., Daluiski, A., Heller, R., and Lusis, A. J. (1994). Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice. Biochem. Genet. 32:397–407.
ISAG: International Society for Animal Genetics. (1996). Proceedings of the XXVth International Conference on Animal Genetics, Tours, France.
Ishida, B. Y., and Paigen, B. (1989). Atherosclerosis in the mouse. In Lusis, A. J., and Sparkes, R. S. (eds.), Genetic Factors in Atherosclerosis. Approaches and Model Systems, S Karger AG, Basel. pp 189–222.
Jacob, H. J., Lindpaintner, K., Lincoln, S. E., Kusumi, K., Bunker, R. K., Mao, Y.-P., Ganten, D., Dzau, V. J., and Lander, E. S. (1991). Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67:213–224.
Jiang, C., and Zeng, Z.-B. (1995). Multiple trait analysis of genetic mapping for quantitative trait loci. Genetics 140:1111–1127.
Johnson, P. R. J., and Gregoire, F. (1994). Animal models of genetic obesity: Peripheral tissue changes. In Bouchard, C. (ed.), The Genetics of Obesity, CRC Press, Boca Raton, FL, pp. 161–179.
Johnson, T. E., DeFries, J. C., and Markel, P. D. (1992). Mapping quantitative trait loci for behavioral traits in the mouse. Behav. Genet. 22:635–653.
Keightley, P. D., Hardge, T., May, L., and Bulfield, G. (1996). A genetic map of quantitative trait loci for body weight in the mouse. Genetics 142:227–235.
King, R. C., and Stanfield, W. D. (1985). A Dictionary of Genetics, 3rd ed., Oxford University Press, New York.
Kleyn, P. W., Fan, W., Kovats, S. G., Lee, J. J., Pulido, J. C., Wu, Y., Berkemeier, L. R., Misumi, D. J., Holmgren, L., Charlat, O., Woolf, E. A., Tayber, O., Brody, T., Shu, P., Hawkins, F., Kennedy, B., Baldini, L., Ebeling, C., Alperin, G. D., Deeds, J., Lakey, N. D., Culpepper, J., Chen, H., Glucksmannkuis, M. A., Carlson, G. A., Duyk, G. M., and Moore, K. J. (1996). Identification and characterization of the mouse obesity gene tubby: A member of a novel gene family. Cell 85:281–290.
Kirk, E. A., Moe, G. L., Caldwell, M. T., Lernmark, J. A., Wilson, D. L., and LeBoeuf, R. C. (1995). Hyper-and hypo-responsiveness to dietary fat and cholesterol among inbred mice: Searching for level and variability genes. J. Lipid Res. 36:1522–1532.
Kono, D. W., Burlingame, R. W., Owens, D. G., Kuramochi, A., Balderas, R. S., Balomenos, D., and Theofilopoulos, A. N. (1994). Lupus susceptibility loci in New Zealand mice. Proc. Natl. Acad. Sci. USA 91:10168–10172.
Kwon, H. J., Bultman, S. J., Loffler, C., Chen, W.-J., Furdon, P. J., Powell, J. G., Usala, A.-L., Wilkison, W., Hansmann, I., and Woychik, R. P. (1994). Molecular structure and chromosomal mapping of the human homolog of the agouti gene. Proc. Natl. Acad. Sci. USA 91:9760–9764.
Lander, E. S., and Botstein, D. (1989). Mapping Meudelian factors underlying quantitative traits using RFLP maps. Genetics 121:185–99.
Lander, E., and Kruglyak, L. (1995). Genetic dissection of complex traits: Guidelines for interpreting and reporting linkage results. Nature Genet. 11:241–247.
Lander, E. S., and Schork, N. J. (1994). Genetic dissection of complex traits. Science 265:2037–2048.
Lang, B. J., and Legates, J. E. (1969). Rate, composition and efficiency of growth in mice selected for large and small body weight. Theor. Appl. Genet. 39:306–314.
Lembertas, A. V., Fisler, J. S., Warden, C. H., Wen, P.-Z., Xia, Y.-R., and Lusis, A. J. (1996). A locus on the X chromosome is linked to body length in mice. Mammal. Genome 7:171–173.
Lembertas, A. V., Pérusse, L., Chagnon, Y. C., Fisler, J. S., Warden, C. H., Ting, K., Purcell-Huynh, D. A., Dionne, F. T., Gagnon, J., Nadeau, A., Lusis, A. J., and Bouchard, C. (1997). Genes contributing to body fat on mouse chromosome 2 and the homologous region of human chromosome 20. (submitted for publication).
Lusis, A. J., and Sparkes, R. S. (1989). Chromosomal organization of genes involved in plasma lipoprotein metabolism: Human and mouse “fat maps.” In Lusis, A. J., and Sparkes, R. S. (eds.), Genetic Factors in Atherosclerosis: Approaches and Model Systems, S Karger AG, Basel, pp. 79–94.
Lyon, M. F., and Searle, A. G. (1989). Genetic Variants and Stains of the Laboratory Mouse, 2nd ed., Oxford University Press, Oxford, New York.
MacArthur, J. (1944). Genetics of body size and related characters. I. Selection of small and large races of the laboratory mouse. Am. Nat. 78:142–157.
McAleer, M. A., Reifsnyder, P., Palmer, S. M., Prochazka, M., Love, J. M., Copeman, J. B., Powell, E. E., Rodrigues, N. R., Prins, J. B. Serreze, D. V., DeLarato, N. H., Wicker, L. S., Peterson, L. B., Schork, N. J., Todd, J. A., and Leiter, E. H. (1995). Crosses of NOD mice with the related NON strain. A polygenic model for IDDM. Diabetes 44:1186–1195.
Medrano, J. F., Pomp, D., Sharrow, L., Bradford, G. E., Downs, T. R., and Frohman, I. (1991). Growth hormone and IGF-I measurements in high growth (hg) mice. Genet. Res. Cambridge 58:67–74.
Medrano, J. F., Pomp, D., Taylor, B. A., and Bradford, G. E. (1992). The high growth gene (hg) in mice is located in chromosome 10 linked to Igf-1. In Whelan, W. J., Ahamd, F., Bialy, H., et al. (eds.), Advances in Gene Technology: Feeding the World in the 21st Century, The Miami Bio/Technology Winter Symposium, Vol. 1, p. 12.
Miller, E. R., and Ullrey, D. E. (1987). The pig as a model for human nutrition. Annu. Rev. Nutr. 7:361.
Moller, D. E., and Flier, J. S. (1991). Insulin resistance mechanisms, syndromes and implications. N. Engl. J. Med. 325:938–948.
Moody, D. E., Pomp, D., and Nielsen, M. K. (1997). Variability in metabolic rate, feed intake and fatness in selection and inbred lines of mice (submitted for publication).
Naggert, J. K., Fricker, L. D., Varlamov, O., Nishina, P. M., Rouille, Y., Steiner, D. F., Carroll, R. J., Paigen, B. J., and Leiter, E. H. (1995). Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nature Genet. 10:135–142.
Nielsen, M. K., Jones, L. D., Freking, B. A., and DeShazer, J. A. (1997). Divergent selection for heat loss in mice. I. Selection applied and direct response through fifteen generation. J. Anim. Sci. (in press).
Noben-Trauth, K., Naggert, J. K., North, M. A., and Nishina, P. M. (1996). A candidate gene for the mouse mutation tubby. Nature 380:534–538.
Oberbauer, A. M., Stern, J. S., Johnson, P. R., Horwitz, B. A., German, J. B., Phinney, S. D., Beermann, D. H., Pomp, D., and Murray, J. D. (1997). Body composition of inactivated growth hormone (oMTla-oGH) transgenic mice: Generation of an obese phenotype. (submitted for publication).
Paigen, B. (1995). Genetics of responsiveness to high-fat and high-cholesterol diets in the mouse. Am. J. Clin. Nutr. 62:458S-462S.
Paigen, B., Mitchell, D., Reue, K., Morrow, A., Lusis, A. J., and LeBoeuf, R. C. (1987). Ath1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice. Proc. Natl. Acad. Sci. USA 84:3763–3767.
Pomp, D., Foster, S., Cushman, M. A., and Eisen, E. J. (1995). Identification of genes controlling quantitative reproduction traits in mice. Biol. Reprod. 52(Suppl. 1):61.
Pomp, D., Foster, S., Cushman, M. A., Beck, G., and Eisen, E. J. (1996). Quantitative trait loci for murine body weight and fatness in a large F2 cross between high and low growth selection lines. In Proceedings XXV International Conference on Animal Genetics (ISAG). Tours, France, abstract E040, p. 175.
Pomp, D., Drudik, D. D., Cushman, M. A., Foster, S., Beck, G., Siewerdt, F., Zeng, Z. B., and Eisen, E. J. (1997). Detection of QTL for adiposity and body weight in a cross between high growth and wild strains of mice (submitted for publication).
Pravenec, M., Gauguier, D., Schott, J. J., Buard, J., Kren, V., Bila, V., Szpirer, C., Szpirer, J., Wang, J.-M., Huang, H., St. Lezin, E., Spence, M. A., Flodman, P., Printz, M., Lathrop, G. M., Vergnaud, G., and Kurtz, T. W. (1995). Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains. J. Clin. Invest. 96:1973–1978.
Purcell-Huynh, D. A., Weinreb, A., Castellani, L. W., Mehrabian, M., Doolittle, M. H., and Lusis, A. J. (1995). Genetic factors in lipoprotein metabolism. Analysis of a genetic cross between inbred mouse strains NZB/BINJ and SM/J using a complete linkage map approach. J. Clin. Invest. 96:1845–1858.
Pursel, V. G., Pinkert, C. A., Miller, K. F., Bolt, D. J., Cambell, R. G., Palmiter, R. D., Brinster, R. L., and Hammer, R. E. (1989). Genetic engineering of livestock. Science 244:1281–1288.
Rance, K. A., Hastings, I. M., Hill, W. G., and Keightley, P. D. (1994). Mapping of putative QTL influencing body weight on the X chromosome in mice. Proc. 5th World Congr. Genet. Appl. Livestock Prod. 21:268–271.
Rapacz, J., and Hasler-Rapacz, J. (1989). Animal models: The pig. In Lusis, A. J., and Sparkes, R. S. (eds.), Genetic Factors in Atherosclerosis: Approaches and Model Systems, pp. 139–169.
Rice, T., Tremblay, A., Dériaz, O., Pérusse, L., Rao, D. C., and Bouchard, C. (1996). Genetic pleiotropy for resting metabolic rate with fat-free mass and fat mass: The Québec family study. Obesity Res. 4:125–131.
Rich, S. S. (1990). Mapping genes in diabetes. Diabetes 39:1315–1319.
Robeson, B. L., Eisen, E. J., and Leatherwood, J. M. (1981). Adipose cellularity, serum glucose, insulin and cholesterol in polygenic obese mice fed high-fat or high carbohydrate diets. Growth 45:198–215.
Rohrer, G. A., Alexander, L. J., Hu, Z., Smith, T. P. L., Keele, J. W., and Beattie, C. W. (1996). A comprehensive map of the porcine genome. Genome Res. 6:371–391.
Ross, R. (1986). N. Engl. J. Med. 314:488–500.
Rothschild, M. F., Liu, H.-C., Tuggle, C. K., Yu, T.-P., and Wang, L. (1995). Analysis of pig chromosome 7 genetic markers for growth and carcass performance traits. J. Anim. Breed. Genet. 112:341–348.
Rubin, E. M., and Smith, D. J. (1994). Atherosclerosis in mice: Getting to the heart of a polygenic disorder. Trends Genet. 10:199–203.
Saltzman, E., and Roberts, S. B. (1995). The role of energy expenditure in energy regulation: findings from a decade of research. Nutr. Rev. 53:209–220.
Sax, K. (1923). The association of size differences with seed-coat pattern and pigmentation in Phaseolus vulgaris. Genetics 8:552–560.
Schuller, G. D., Boguski, M. S., Stewart, E. A., Stein, L. D., Gape, G., Rice, K., White, R. E., Rodriguez-Tcme, P., Aggarwal, A., Bajorek, E., Bentolila, S., Birren, B. B., Butler, A., Castle, A. B., Chiannilkulchai, N., Chu, A., Clee, C., Cowles, S., Day, P. J. R., Dibling, T., Drouot, N., Dunham, I., Duprat, S., East, C., Edwards, C., Fan, J.-B., Fang, N., Fizames, C., Garrett, C., Green, L., Hadley, D., Harris, M., Harrison, P., Brady, S., Hicks, A., Holloway, E., Hui, L., Hussain, S., Louis-Dit-Sully, C., Ma, J., MacGilvery, A., Mader, C., Maratukulam, A., Matise, T. C., McKusick, K. B., Morissette, J., Mungall, A., Muselet, D., Nusbaum, H. C., Page, D. C., Peck, A., Perkins, S., Piercy, M., Qin, F., Quackenbush, J., Ranby, S., Reif, T., Rozen, S., Sanders, C., She, X., Silva, J., Slonim, D. K., Soderlund, C., Sun, W.-L., Tabar, P., Thangarajah, T., Vega-Czarny, N., Vollrath, D., Voyticky, S., Wilmer, T., Wu, X., Adams, M. D., Auffray, C., Walter, N. A. R., Brandon, R., Dehejia, A., Goodfellow, P. N., Houlgatte, R., Hudson, J. R., Jr., Ide, S. E., Iorio, K. R., Lee, W. Y., Seki, N., Nagase, T., Ishikawa, K., Nomura, N., Phillips, C., Polymeropoulos, M. H., Sandusky, M., Schmitt, K., Berry, R., Swanson, K., Torres, R., Venter, J. C., Sikela, J. M., Beckmann, J. S., Weissenbach, J., Myers, R. M., Cox, D. R., James, M. R., Bentley, D., Deloukas, P., Lander, E. S., and Hudson, T. J. (1996). A gene map of the human genome. Science 274:540–546.
Sharp, G. J., Hill, W. G., and Robertson, A. (1984). Effects of selection on growth, body composition and food intake in mice. I. Responses in selected traits. Genet. Res. 43:75–92.
Sims, E. A. H., Danforth, E., and Horton, E. (1973). Effects of experimental obesity in man. Recent Prog. Horm. Res. 29:457–496.
Soller, M. (1994). Marker assisted selection—An overview. Anim. Biotechnol. 5(2):193–207.
Sturtevant, A. H. (1913). The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association. J. Exp. Zool. 14:43–59.
Svenson, K. L., Warden, C. H., Fisler, J. S., and Lusis, A. J. (1994). Two novel loci control HDL cholesterol levels in a multigenic mouse model (abstract). FASEB J. 8:A542.
Taylor, B. A., and Phillips, S. J. (1996). Detection of obesity QTLs on mouse chromosomes 1 and 7 by selective DNA pooling. Genomics 34:389–398.
Warden, C. H., Fisler, J. S., Pace, M. J., Svenson, K. L., and Lusis, A. J. (1993). Coincidence of genetic loci for plasma cholesterol levels and obesity in a multifactorial mouse model. J. Clin. Invest. 92:773–779.
Warden, C. H., Fisler, J. S., Shoemaker, S. M., Wen, P.-Z., Svenson, K. L., Pace, M. J., and Lusis, A. J. (1995). Identification of four chromosomal loci determining obesity in a multifactorial mouse model. J. Clin. Invest. 95:1545–1552.
Weber, J. L., and May, P. E. (1989). Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. Hum. Genet. 44:388–396.
West, D. B., Boozer, C. N., Moody, D. L., and Atkinson, R. L. (1992). Dietary obesity in nine inbred mouse strains. Am. J. Physiol. 262:R1025-R1032.
West, D. B., Goudey-Lefevre, J., York, B., and Truett, G. E. (1994a). Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model. J. Clin. Invest. 94:1410–1416.
West, D. B., Waguespack, J., York, B., Goudey-Lefevre, J., and Price, R. A. (1994b). Genetics of dietary obesity in AKR/J × SWR/J mice: Segregation of the trait and identification of a linked locus on chromosome 4. Mammal. Genome 5:546–552.
West, D. B., Truett, G. E., Goudey-Lefevre, J., and York, B. (1995). Loci on chromosomes 4, 7, 9, 12, & 15 control a significant proportion of the dietary obesity phenotype in the mouse. FASEB J. 9(3):A722.
Williams, R. R., Hunt, S. C., Hasstedt, S. J., Hopkins, P. N., Wu, L. L., Berry, T. D., Stults, M., Barlow, G. K., and Kuida, H. (1990). Genetics of hypertension: What we know and don't know. Clin. Exp. Hyper. A12:865–876.
Williamson, R., and Kessling, A. M. (1990). The problem of polygenic disease. Ciba Foundation Symposium 149, pp. 63–80.
York, B., Lei, K., and West, D. B. (1996). Sensitivity to dietary obesity linked to a locus on chromosome 15 in a CAST/Ei × C57BL/6J F2 intercross. Mammal. Genome 7:677–681.
Zeng, Z.-B. (1994). Precision mapping of quantitative trait loci. Genetics 136:1457–1465.
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432.
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Pomp, D. Genetic Dissection of Obesity in Polygenic Animal Models. Behav Genet 27, 285–306 (1997). https://doi.org/10.1023/A:1025631813018
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DOI: https://doi.org/10.1023/A:1025631813018