Quantitative trait loci for energy balance traits in an advanced intercross line derived from mice divergently selected for heat loss.

Larry J Leamy,Merlyn K Nielsen,Stephanie R Thorn,William Valdar,Daniel Pomp,Kari Elo

doi:10.7717/peerj.392

Abstract

Obesity in human populations, currently a serious health concern, is considered to be the consequence of an energy imbalance in which more energy in calories is consumed than is expended. We used interval mapping techniques to investigate the genetic basis of a number of energy balance traits in an F11 advanced intercross population of mice created from an original intercross of lines selected for increased and decreased heat loss. We uncovered a total of 137 quantitative trait loci (QTLs) for these traits at 41 unique sites on 18 of the 20 chromosomes in the mouse genome, with X-linked QTLs being most prevalent. Two QTLs were found for the selection target of heat loss, one on distal chromosome 1 and another on proximal chromosome 2. The number of QTLs affecting the various traits generally was consistent with previous estimates of heritabilities in the same population, with the most found for two bone mineral traits and the least for feed intake and several body composition traits. QTLs were generally additive in their effects, and some, especially those affecting the body weight traits, were sex-specific. Pleiotropy was extensive within trait groups (body weights, adiposity and organ weight traits, bone traits) and especially between body composition traits adjusted and not adjusted for body weight at sacrifice. Nine QTLs were found for one or more of the adiposity traits, five of which appeared to be unique. The confidence intervals among all QTLs averaged 13.3 Mb, much smaller than usually observed in an F2 cross, and in some cases this allowed us to make reasonable inferences about candidate genes underlying these QTLs. This study combined QTL mapping with genetic parameter analysis in a large segregating population, and has advanced our understanding of the genetic architecture of complex traits related to obesity.

Highlights

Energy balance in biological organisms is achieved when the amount of energy consumed equals that expended
Energy consumption and expenditure QTLs The two QTLs we discovered for heat loss (HL) were far fewer than the nine QTLs found for this same trait by Moody et al (1999) in their HB mouse population, and mapped to different positions
We conducted an extensive genome-wide scan for a wide variety of metabolism traits within an advanced intercross line derived from lines divergently selected for heat loss

Summary

Introduction

Energy balance in biological organisms is achieved when the amount of energy consumed equals that expended. It is interesting that many of the QTLs found far map to different sites than those affecting body weight and adiposity measures (Allan, Eisen & Pomp, 2005; Kelly et al, 2010; Leamy et al, 2012) This appears to be the case for QTLs affecting energy expenditure as assessed from voluntary exercise (primarily wheelrunning) traits in mice (Lightfoot et al, 2007; Lightfoot et al, 2008; Lightfoot et al, 2010; Leamy, Pomp & Lightfoot, 2008; Leamy, Pomp & Lightfoot, 2009a; Leamy, Pomp & Lightfoot, 2009b; Nehrenberg et al, 2010; Kelly et al, 2010; Mathes et al, 2011)

Methods

Results

Discussion

Conclusion