Abstract
Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress” by James Neel (Am J Hum Genet 14:353–362, 1962).
Type 2 diabetes (T2D) is a complex metabolic disorder in which both genetic and environmental factors play roles in the etiology. Advances in genetic analyses brought tremendous successes in identifying genetic components of common T2D and monogenic form of diabetes such as maturity-onset diabetes of the young (MODY). Large-scale genome-wide association studies identified more than 70 loci of T2D in various populations, which dramatically enhance our understanding of molecular etiology of T2D. In particular, TCF7L2, which is the most prominent genetic susceptibility of T2D, is extensively studied including functional impact. MODY is considered to be a monogenic form of diabetes, but complexity of the disorder is revealed; indeed, genetic causalities were identified in only <15% of MODY patients in Japan. More than 50 years ago, Neel made two notions on genetics of T2D: one is calling T2D as geneticist’s nightmare and the other is thrifty genotype hypothesis. These notions are challenged, partly solved, with the modern genetic advances and are focused in this chapter.
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Inoue, I., Nakaoka, H. (2017). Genetics of Diabetes: Are They Thrifty Genotype?. In: Saitou, N. (eds) Evolution of the Human Genome I. Evolutionary Studies. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56603-8_13
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DOI: https://doi.org/10.1007/978-4-431-56603-8_13
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