Fine-mapping of Obesity-related Quantitative Trait Loci in an F9/10 Advanced Intercross Line

Overview

Journal Obesity (Silver Spring)

Specialties Endocrinology
Nutritional Sciences
Physiology

Date 2009 Nov 14

PMID 19910941

Citations 22

Authors

Gloria L Fawcett

Joseph P Jarvis

Charles C Roseman

Bing Wang

Jason B Wolf

James M Cheverud

Affiliations

Soon will be listed here.

Abstract

Obesity develops in response to a combination of environmental effects and multiple genes of small effect. Although there has been significant progress in characterizing genes in many pathways contributing to metabolic disease, knowledge about the relationships of these genes to each other and their joint effects upon obesity lags behind. The LG,SM advanced intercross line (AIL) model of obesity has been used to characterize over 70 loci involved in fatpad weight, body weight, and organ weights. Each of these quantitative trait loci (QTLs) encompasses large regions of the genome and require fine-mapping to isolate causative sequence changes and possible mechanisms of action as indicated by the genetic architecture. In this study we fine-map QTLs first identified in the F(2) and F(2/3) populations in the combined F(9/10) advanced intercross generations. We observed significantly narrowed QTL confidence regions, identified many single QTL that resolve into multiple QTL peaks, and identified new QTLs that may have been previously masked due to opposite gene effects at closely linked loci. We also present further characterization of the pleiotropic and epistatic interactions underlying these obesity-related traits.

Citing Articles

C57BL/6J mice as a polygenic developmental model of diet-induced obesity.

Chu D, Malinowska E, Jura M, Kozak L Physiol Rep. 2017; 5(7).

PMID: 28400497 PMC: 5392500. DOI: 10.14814/phy2.13093.

Using whole-genome sequences of the LG/J and SM/J inbred mouse strains to prioritize quantitative trait genes and nucleotides.

Nikolskiy I, Conrad D, Chun S, Fay J, Cheverud J, Lawson H BMC Genomics. 2015; 16:415.

PMID: 26016481 PMC: 4445795. DOI: 10.1186/s12864-015-1592-3.

Fine-mapping QTLs in advanced intercross lines and other outbred populations.

Gonzales N, Palmer A Mamm Genome. 2014; 25(7-8):271-92.

PMID: 24906874 PMC: 4126234. DOI: 10.1007/s00335-014-9523-1.

The effect of dietary fat intake on hepatic gene expression in LG/J AND SM/J mice.

Partridge C, Fawcett G, Wang B, Semenkovich C, Cheverud J BMC Genomics. 2014; 15:99.

PMID: 24499025 PMC: 4028868. DOI: 10.1186/1471-2164-15-99.

QTL mapping in outbred populations: successes and challenges.

Solberg Woods L Physiol Genomics. 2013; 46(3):81-90.

PMID: 24326347 PMC: 4073892. DOI: 10.1152/physiolgenomics.00127.2013.

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