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Open Access Highly Accessed Research article

An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2

Jaemin Kim1, Taeheon Lee2, Tae-Hun Kim3, Kyung-Tai Lee3* and Heebal Kim124*

Author Affiliations

1 Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea

2 Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea

3 Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Suwon, 441-706, Republic of Korea

4 C&K Genomics, Seoul National University Research Park, Seoul, 151-919, Republic of Korea

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BMC Genomics 2012, 13:711  doi:10.1186/1471-2164-13-711

Published: 19 December 2012

Abstract

Background

Traditional candidate gene approach has been widely used for the study of complex diseases including obesity. However, this approach is largely limited by its dependence on existing knowledge of presumed biology of the phenotype under investigation. Our combined strategy of comparative genomics and chromosomal heritability estimate analysis of obesity traits, subscapular skinfold thickness and back-fat thickness in Korean cohorts and pig (Sus scrofa), may overcome the limitations of candidate gene analysis and allow us to better understand genetic predisposition to human obesity.

Results

We found common genes including FTO, the fat mass and obesity associated gene, identified from significant SNPs by association studies of each trait. These common genes were related to blood pressure and arterial stiffness (P = 1.65E-05) and type 2 diabetes (P = 0.00578). Through the estimation of variance of genetic component (heritability) for each chromosome by SNPs, we observed a significant positive correlation (r = 0.479) between genetic contributions of human and pig to obesity traits. Furthermore, we noted that human chromosome 2 (syntenic to pig chromosomes 3 and 15) was most important in explaining the phenotypic variance for obesity.

Conclusions

Obesity genetics still awaits further discovery. Navigating syntenic regions suggests obesity candidate genes on chromosome 2 that are previously known to be associated with obesity-related diseases: MRPL33, PARD3B, ERBB4, STK39, and ZNF385B.

Keywords:
Obesity; Synteny; Comparative genomics; Heritability; Back-fat thickness; Subscapular skinfold thickness; Chromosome 2; Pig; Human