Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies.

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Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies.

J Diabetes Complications. 2017 Oct;31(10):1549-1561

Authors: da Fonseca ACP, Mastronardi C, Johar A, Arcos-Burgos M, Paz-Filho G

Abstract
BACKGROUND: Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors.
OBJECTIVES: To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function. Furthermore, we discuss the technologies that are available for the genetic diagnosis of obesity.
RESULTS: Several studies reported that single gene variants cause Mendelian forms of obesity, determined by mutations of major effect in single genes. Rare, non-syndromic forms of obesity are a result of loss-of-function mutations in genes that act on the development and function of the hypothalamus or the leptin-melanocortin pathway. These variants disrupt enzymes and receptors that play a role in energy homeostasis, resulting in severe early-onset obesity and endocrine dysfunctions. Different approaches and technologies have been used to understand the genetic background of obesity. Currently, whole genome and whole exome sequencing are important diagnostic tools to identify new genes and variants associated with severe obesity, but other approaches are also useful at individual or population levels, such as linkage analysis, candidate gene sequencing, chromosomal microarray analysis, and genome-wide association studies.
CONCLUSIONS: The understanding of the genetic causes of obesity and the usefulness and limitations of the genetic diagnostic approaches can contribute to the development of new personalized therapeutic targets against obesity.

PMID: 28735903 [PubMed – indexed for MEDLINE]

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