Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction
- 661 Downloads
Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form.
We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions.
By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution ideograms and their name, precise chromosome band location and description were summarized in tabular form.
Meaningful correlations in the obesity phenotype and associated human infertility and reproduction are represented with the location of genes on chromosome ideograms along with description of the gene and position in tabular form. These high resolution chromosome ideograms and tables will be useful in genetic awareness and counseling, diagnosis and treatment to improve clinical outcomes.
KeywordsObesity Obesity susceptibility genes Gene symbols Human infertility and reproduction High resolution chromosome ideogram
We thank Carla Meister for expert preparation of the manuscript, Dr. Syed Rafi for assistance in literature review and Lorie Gavulic for excellent artistic design and preparation of chromosome ideograms.
Partial funding support was provided by the Prader-Willi Syndrome Association (USA), the Headley Family Scholarship, the National Institute of Child Health and Human Development (NICHD) HD02528 and from the Angelman, Rett and Prader-Willi Syndromes Consortium (U54 HD06122) which is part of the National Institute of Health (NIH) Rare Disease Clinical Research Network (RDCRN) supported through collaboration between the NIH Office of Rare Disease Research (ORDR) at the National Center of Advancing Translational Science (NCATS) and NICHD. The content is solely the responsibility of the authors and does not necessarily represent the office views of the National Institutes of Health.
Conflict of interest
The authors declare no conflict of interest.
- 6.Silber SJ, Barbey N. Scientific molecular basis for treatment of reproductive failure in the human: an insight into the future. Biochim Biophys Acta. 1822;2012:1981–96.Google Scholar
- 17.Cheung WW, Mao P. Recent advances in obesity: genetics and beyond. ISRN Endocrinol. 2012; 536905.Google Scholar
- 35.El Inati E, Muller J, Viville S. Autosomal mutations and human spermatogenic failure. Biochim Biophys Acta. 1822;2012:1873–9.Google Scholar
- 45.D’Angelo CS, Da Paz JA, Kim CA, Bertola DR, Castro CI, Varela MC, et al. Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning disabilities and behavioral problems. Eur J Med Genet. 2006;49:451–60.CrossRefPubMedGoogle Scholar
- 48.van den Berg L, de Waal HD, Han JC, Ylstra B, Eijk P, Nesterova M, et al. Investigation of a patient with a partial trisomy 16q including the fat mass and obesity associated gene (FTO): fine mapping and FTO gene expression study. Am J Med Genet A. 2010;152A:630–7.CrossRefPubMedCentralPubMedGoogle Scholar
- 51.D’Angelo CS, Jehee FS, Koiffmann CP. An inherited atypical 1 Mb 22q11.2 deletion within the DGS/VCFS 3 Mb region in a child with obesity and aggressive behavior. Am J Med Genet A. 2007;143A:1928–32.Google Scholar