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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Multifactorial Inheritance

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Disease relevance of Multifactorial Inheritance


High impact information on Multifactorial Inheritance

  • We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance [5].
  • Here we show oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a parent-of-origin effect at RET [6].
  • Generalized resistance to thymic deletion in the NOD mouse; a polygenic trait characterized by defective induction of Bim [7].
  • In most pedigrees, serum cholesterol appeared to be a purely polygenic trait, with 54% heritability [8].
  • Recent data have demonstrated that BBS may be inherited either as a simple Mendelian recessive or as an oligogenic trait, since mutations at two loci are sometimes required for pathogenesis [9].

Biological context of Multifactorial Inheritance

  • The ability to generate serum CSF after administration of LPS is controlled by a single autosomal dominant gene, while the splenic CFC response to LPS follows the characteristic patterns of a polygenic inheritance control [10].
  • It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles [11].
  • This family suggests that a rare form of CoA could be the result of an autosomal dominant mutation with incomplete penetrance and variable expressivity rather than polygenic inheritance [12].
  • The sensitivities to enflurane and isoflurane is F1 progeny of reciprocal crosses between ddN and C57BL mice revealed that in the ddN strain enflurane resistance is an incompletely dominant or polygenic character, isoflurane resistance in ddN strain is an autosomal recessive character and both are controlled by genes on the sex (X) chromosome [13].
  • Analysis of the collected date revealed the following results: Testing of inheritance pattern Fitness of OPLL to the hypotheses of simple recessive inheritance, simple dominant inheritance and multifactorial inheritance was tested, but fitness to any one of these hypotheses was statistically denied [14].

Anatomical context of Multifactorial Inheritance

  • Therefore, a possible involvement of the human PDE3A gene in these polygenic traits is discussed, taking into account the prominent role of the rat PDE3A gene product in the antilipolytic action of insulin in adipocytes [15].

Associations of Multifactorial Inheritance with chemical compounds

  • The newly-bred red grapevine variety 'Regent' has multiple field-resistance to fungal diseases inherited as polygenic traits, while 'Lemberger' is a traditional fungus-susceptible cultivar [16].
  • The data gave the best fit for a polygenic inheritance with a heritability of 66 +/- 11% for SLE and 44 +/- 10% for discoid LE [17].
  • Variation in the hepatotoxic effects of carbon disulphide in the rat: evidence for polygenic inheritance [18].
  • The logic behind the use of metric, polygenic traits in zygosity diagnosis is also presented, together with tables giving the odds against a dizygotic twin pair showing various degrees of similarity in ponderal index, in cephalic index, and in Slater's Z score, a measure of fingerprint similarity [19].
  • CONCLUSION: These observations indicate that the 4NQO-induced TC in the rat is a multifactorial disease of a polygenic trait [20].

Gene context of Multifactorial Inheritance

  • Serum IGF-1 levels in the F2 progeny were relatively normal in distribution, but showed a greater range than either progenitor, indicating that serum IGF-1 level is a polygenic trait with an estimated heritability of 52% [21].
  • The specific genetic background of the Mediterranean population could make it difficult for MC4R mutations to produce an essentially polygenic trait such as common obesity, at least during childhood [22].
  • These approaches showed that several spontaneous and engineered mutations interact with 129/Sv-derived susceptibility genes to enhance or suppress susceptibility; two of these mutations (Ter and Trp53) revealed novel linkages for susceptibility genes in sensitized polygenic trait analysis [23].
  • Most studies support a polygenic inheritance with a susceptibility locus (designated IGAD1) in the MHC, but its exact location is still controversial [24].
  • Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance [25].

Analytical, diagnostic and therapeutic context of Multifactorial Inheritance


  1. Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss. Noben-Trauth, K., Zheng, Q.Y., Johnson, K.R. Nat. Genet. (2003) [Pubmed]
  2. Genetic variants of the human obesity (OB) gene: association with body mass index in young women, psychiatric symptoms, and interaction with the dopamine D2 receptor (DRD2) gene. Comings, D.E., Gade, R., MacMurray, J.P., Muhleman, D., Peters, W.R. Mol. Psychiatry (1996) [Pubmed]
  3. Adult-onset Alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model. Sundberg, J.P., Silva, K.A., Li, R., Cox, G.A., King, L.E. J. Invest. Dermatol. (2004) [Pubmed]
  4. Familial aggregation of idiopathic dilated cardiomyopathy: clinical features and pedigree analysis in 14 families. Zachara, E., Caforio, A.L., Carboni, G.P., Pellegrini, A., Pompili, A., Del Porto, G., Sciarra, A., Bosman, C., Boldrini, R., Prati, P.L. British heart journal. (1993) [Pubmed]
  5. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Stoetzel, C., Laurier, V., Davis, E.E., Muller, J., Rix, S., Badano, J.L., Leitch, C.C., Salem, N., Chouery, E., Corbani, S., Jalk, N., Vicaire, S., Sarda, P., Hamel, C., Lacombe, D., Holder, M., Odent, S., Holder, S., Brooks, A.S., Elcioglu, N.H., Da Silva, E., Rossillion, B., Sigaudy, S., de Ravel, T.J., Alan Lewis, R., Leheup, B., Verloes, A., Amati-Bonneau, P., Mégarbané, A., Poch, O., Bonneau, D., Beales, P.L., Mandel, J.L., Katsanis, N., Dollfus, H. Nat. Genet. (2006) [Pubmed]
  6. Segregation at three loci explains familial and population risk in Hirschsprung disease. Gabriel, S.B., Salomon, R., Pelet, A., Angrist, M., Amiel, J., Fornage, M., Attié-Bitach, T., Olson, J.M., Hofstra, R., Buys, C., Steffann, J., Munnich, A., Lyonnet, S., Chakravarti, A. Nat. Genet. (2002) [Pubmed]
  7. Generalized resistance to thymic deletion in the NOD mouse; a polygenic trait characterized by defective induction of Bim. Liston, A., Lesage, S., Gray, D.H., O'Reilly, L.A., Strasser, A., Fahrer, A.M., Boyd, R.L., Wilson, J., Baxter, A.G., Gallo, E.M., Crabtree, G.R., Peng, K., Wilson, S.R., Goodnow, C.C. Immunity (2004) [Pubmed]
  8. Evidence that men with familial hypercholesterolemia can avoid early coronary death. An analysis of 77 gene carriers in four Utah pedigrees. Williams, R.R., Hasstedt, S.J., Wilson, D.E., Ash, K.O., Yanowitz, F.F., Reiber, G.E., Kuida, H. JAMA (1986) [Pubmed]
  9. Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus. Badano, J.L., Kim, J.C., Hoskins, B.E., Lewis, R.A., Ansley, S.J., Cutler, D.J., Castellan, C., Beales, P.L., Leroux, M.R., Katsanis, N. Hum. Mol. Genet. (2003) [Pubmed]
  10. Genetic control of lipopolysaccharide induced generation of serum colony stimulating factor and proliferation of splenic granulocyte/macrophage precursor cells. Apte, R.N., Pluznik, D.H. J. Cell. Physiol. (1976) [Pubmed]
  11. HLA-DP: a class II restriction molecule involved in epitope spreading during the development of multiple sclerosis. Yu, M., Kinkel, R.P., Weinstock-Guttman, B., Cook, D.J., Tuohy, V.K. Hum. Immunol. (1998) [Pubmed]
  12. Familial coarctation of the aorta in three generations. Stoll, C., Alembik, Y., Dott, B. Ann. Genet. (1999) [Pubmed]
  13. Strain-differences of sensitivity to volatile anesthetics and their genetic character in mice. Tanaka, T., Ogli, K., Komatsu, H., Nogaya, J., Yokono, S. Journal of anesthesia. (1993) [Pubmed]
  14. Genetic study on ossification of posterior longitudinal ligament. Tanikawa, E., Furuya, K., Nakajima, H. Bull. Tokyo Med. Dent. Univ. (1986) [Pubmed]
  15. Molecular cloning and chromosomal assignment of the human homologue of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene involved in fat metabolism located at 11p 15.1. Löbbert, R.W., Winterpacht, A., Seipel, B., Zabel, B.U. Genomics (1996) [Pubmed]
  16. Quantitative trait locus analysis of fungal disease resistance factors on a molecular map of grapevine. Fischer, B.M., Salakhutdinov, I., Akkurt, M., Eibach, R., Edwards, K.J., Töpfer, R., Zyprian, E.M. Theor. Appl. Genet. (2004) [Pubmed]
  17. A family survey of lupus erythematosus. 1. Heritability. Lawrence, J.S., Martins, C.L., Drake, G.L. J. Rheumatol. (1987) [Pubmed]
  18. Variation in the hepatotoxic effects of carbon disulphide in the rat: evidence for polygenic inheritance. Lovell, D.P., Tucker, S.P., Cunningham, V.J. Toxicol. Lett. (1982) [Pubmed]
  19. The diagnosis of zygosity in twins. Lykken, D.T. Behav. Genet. (1978) [Pubmed]
  20. Genetic predisposition to 4NQO-induced tongue carcinogenesis in the rat. Tanuma, J., Hirano, M., Hirayama, Y., Semba, I., Ogawa, K., Shisa, H., Hiai, H., Kitano, M. Medical principles and practice : international journal of the Kuwait University, Health Science Centre. (2005) [Pubmed]
  21. Mapping quantitative trait loci for serum insulin-like growth factor-1 levels in mice. Rosen, C.J., Churchill, G.A., Donahue, L.R., Shultz, K.L., Burgess, J.K., Powell, D.R., Ackert, C., Beamer, W.G. Bone (2000) [Pubmed]
  22. Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity. Miraglia Del Giudice, E., Cirillo, G., Nigro, V., Santoro, N., D'Urso, L., Raimondo, P., Cozzolino, D., Scafato, D., Perrone, L. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  23. Genetic control of susceptibility to spontaneous testicular germ cell tumors in mice. Lam, M.Y., Nadeau, J.H. APMIS (2003) [Pubmed]
  24. MHC susceptibility genes to IgA deficiency are located in different regions on different HLA haplotypes. De la Concha, E.G., Fernandez-Arquero, M., Gual, L., Vigil, P., Martinez, A., Urcelay, E., Ferreira, A., Garcia-Rodriguez, M.C., Fontan, G. J. Immunol. (2002) [Pubmed]
  25. Confirmation and fine mapping of chromosomal regions influencing peak bone mass in mice. Klein, O.F., Carlos, A.S., Vartanian, K.A., Chambers, V.K., Turner, E.J., Phillips, T.J., Belknap, J.K., Orwoll, E.S. J. Bone Miner. Res. (2001) [Pubmed]
  26. A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6. Schwab, S.G., Hallmayer, J., Albus, M., Lerer, B., Eckstein, G.N., Borrmann, M., Segman, R.H., Hanses, C., Freymann, J., Yakir, A., Trixler, M., Falkai, P., Rietschel, M., Maier, W., Wildenauer, D.B. Mol. Psychiatry (2000) [Pubmed]
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