High-Resolution Quantitative Trait Locus Analysis Reveals Multiple Diabetes Susceptibility Loci Mapped to Intervals <800 kb in the Species-ConservedNiddm1iof the GK Rat

• DOI: 10.1534/genetics.106.062208
• Publication Date: 2006-09-02T00:49:30Z
• Authors: Charlotte Granhall; Hee-Bok Park; Hossein Fakhrai-Rad; Holger Luthman
• Keywords: Congenic; Genetic linkage

Abstract Niddm1i, a 16-Mb locus within the major diabetes QTL in diabetic GK rat, causes impaired glucose tolerance congenic NIDDM1I strain. Niddm1i is homologous to both human and mouse regions linked with type 2 susceptibility. We employed multiple analyses of F2 progeny selected for one recombination event combined characterization subcongenic strains. Fine mapping located hyperglycemia 700 kb (Niddm1i4, P = 5 × 10−6). Two adjacent loci were also detected, allele at Niddm1i2 (500 kb) showed glucose-raising effect, whereas it had glucose-lowering effect Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 affecting body weight was identified. Experimental data from subcongenics supported four loci. Sorcs1, two known susceptibility genes region, resides Niddm1i3, while Tcf7l2 maps outside all Multiple-marker analysis incorporating cosegregating as cofactors together genetically can remarkably enhance resolution QTL. The demonstrate that species-conserved composite least (Niddm1i2GK Niddm1i3GK) act opposite directions.