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Chunk #5 — 2. Approaches to Identify Human Obesity Genes — 2.1. Candidate Gene Approach

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Recent advances in obesity: genetics and beyond.
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The candidate gene approach is a hypothesis-driven approach that relies on current understanding on the biology and pathophysiology of the disease. The candidacy of a gene for obesity is based on the following resources: animal models using gene knockout and transgenic approaches; cellular model systems showing their role in metabolic pathways involved in glucose metabolism; linkage and positional cloning studies using extreme cases. The concept of this approach is to identify an association between a variant or mutation within or near the candidate gene and a trait of interest (such as obesity). Candidate gene approach needs to be on a large scale and well powered in order to detect the expected small effects of genetic variants involved in common traits and disease [16, 17]. For example, neuropeptide cocaine- and amphetamine-regulated transcript (CART) was reported as an endogenous satiety factor [18]. Mutational screening of the CART gene in obese children has identified a mutation (Leu34Phe) associated with reduced resting energy expenditure and obesity phenotype [19]. A recent study shows that a small group of adolescents with the Leu34Phe mutation in the