Congenic and bioinformatics analyses resolved a major-effect Fob3b QTL on mouse Chr 15 into two closely linked loci

Zala Prevoršek (Author), Gregor Gorjanc (Author), Beverly Paigen (Author), Simon Horvat (Author)

Abstract

We previously identified a Chr 15 quantitative trait locus (QTL) Fob3b in lines of mice selected for high (Fat line) and low (Lean line) body fat content that represent an unique model of polygenic obesity. Here we genetically dissected the Fob3b interval by analyzing the phenotypes of eight overlapping congenic lines and four F[down]2 congenic intercrosses and prioritized candidates by bioinformatics approaches. Analyses revealed that the Fob3b QTL consists of at least two separate linked QTLs Fob3b1 and Fob3b2. They exhibit additive inheritance and are linked in coupling with alleles originating from the Lean line, decreasing obesity-related traits. In further analyses, we focused on Fob3b1 because it had a larger effect on obesity-related traits than Fob3b2. e.g., the difference between homozygotes for adiposity index (ADI) percentage was 1.22 and 0.77% for Fob3b2, respectively. A set of bioinformatics tools was used to narrow down positional candidates from 85 to 4 high-priority Fob3b1 candidates. A previous single Fob3b QTL was therefore resolved into another two closely linked QTLs, confirming the fractal nature of QTLs mapped at low resolution. The interval of the original Fob3b QTL was narrowed from 22.39 to 4.98 Mbp for Fob3b1 and to 7.68 Mbp for Fob3b2, which excluded the previously assigned candidate squalene epoxidase (Sqle) as the causal gene because it maps proximal to refined Fob3b1 and Fob3b2 intervals. A high-resolution map along with prioritization of Fob3b1 candidates by bioinformatics represents an important step foward to final identification of the Chr 15 obesity QTL.

Keywords

molekularna genetika;debelost;QTL;selekcija;zamaščenost;laboratorijske miši;

Data

Language:	English
Year of publishing:	2010
Typology:	1.01 - Original Scientific Article
Organization:	UL BF - Biotechnical Faculty
UDC:	575
COBISS:	2597000
ISSN:	0938-8990
Views:	1020
Downloads:	270
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Unknown
Type (COBISS):	Not categorized
Pages:	str. 172-185
Volume:	ǂVol. ǂ21
Issue:	ǂno. ǂ3/4
Chronology:	2010
DOI:	10.1007/s00335-010-9252-z
ID:	1033708