Metabolism as a complex genetic trait, a systems biology approach: Implications for inborn errors of metabolism and clinical diseases
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Multifactorial and polygenic inheritance is commonly recognized for many genetic conditions including physical anomalies, complex congenital malformation syndromes, and even common disorders such as adult-onset diabetes mellitus. It has only recently been suggested as a mechanism for inheritance in inborn errors of metabolism. This article reviews the phenomenon of multiple partial enzyme deficiencies leading to clinical relevant biochemical derangements (synergistic heterozygosity) and its implications for other more common disorders such as diabetes and obesity.
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- Cox KB, Hamm DA, Millington DS, et al (2001) Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Hum Mol Genet 10: 2069–2077. doi:10.1093/hmg/10.19.2069.PubMedCrossRefGoogle Scholar
- Goetzman ES, Tian L, Wood PA (2005) Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-alpha during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice. Mol Genet Metab 84: 39–47. doi:10.1016/j.ymgme.2004.09.010.PubMedCrossRefGoogle Scholar
- Hafner RP, Brown GC, Brand MD (1990) Analysis of the control of respiration rate, phosphorylation rate, proton leak rate and protonmotive force in isolated mitochondria using the ‘top-down’ approach of metabolic control theory. Eur J Biochem 188: 313–319. doi:10.1111/j.1432-1033.1990.tb15405.x.PubMedCrossRefGoogle Scholar
- Kelly CL, Rhead WJ, Kutschke DA, et al (1995) Functional correction of short-chain acyl-CoA dehydrogenase deficiency in transgenic mice. Am J Hum Genet 57(Supplement): A52.Google Scholar
- Korf B, Rimoin D, O’Connor J, Pyeritz R (2008) Nature and frequency of genetic disease. In: Rimoin D, O’Connor J, Pyeritz R, Korf B, eds. Principles and Practice of Medical Genetics. Amsterdam: Elsevier, 49–51.Google Scholar
- Rubio JC, Martin MA, del Hoyo P, et al (2000) Molecular analysis of Spanish patients with AMP deaminase deficiency. Muscle Nerve 23: 1175–1178. doi:10.1002/1097-4598(200008)23:8<1175::AID-MUS3>3.0.CO;2-M.PubMedCrossRefGoogle Scholar
- Shoffner JM (2001) Oxidative phosphorylation diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 2367–2424.Google Scholar
- Vladutiu G (2000) Complex phenotypes in metabolic muscle diseases. Muscle Nerve 23: 1157–1159. doi:10.1002/1097-4598(200008)23:8<1157::AID-MUS1>3.0.CO;2-O.PubMedCrossRefGoogle Scholar