RGD Reference Report - High-resolution quantitative trait locus analysis reveals multiple diabetes susceptibility loci mapped to intervals<800 kb in the species-conserved Niddm1i of the GK rat. - Rat Genome Database

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High-resolution quantitative trait locus analysis reveals multiple diabetes susceptibility loci mapped to intervals<800 kb in the species-conserved Niddm1i of the GK rat.

Authors: Granhall, C  Park, HB  Fakhrai-Rad, H  Luthman, H 
Citation: Granhall C, etal., Genetics. 2006 Nov;174(3):1565-72. Epub 2006 Sep 1.
RGD ID: 1599587
Pubmed: PMID:16951059   (View Abstract at PubMed)
PMCID: PMC1667097   (View Article at PubMed Central)
DOI: DOI:10.1534/genetics.106.062208   (Journal Full-text)

Niddm1i, a 16-Mb locus within the major diabetes QTL in the diabetic GK rat, causes impaired glucose tolerance in the congenic NIDDM1I strain. Niddm1i is homologous to both human and mouse regions linked with type 2 diabetes susceptibility. We employed multiple QTL analyses of congenic F2 progeny selected for one recombination event within Niddm1i combined with characterization of subcongenic strains. Fine mapping located one hyperglycemia locus within 700 kb (Niddm1i4, P=5x10(-6)). Two adjacent loci were also detected, and the GK allele at Niddm1i2 (500 kb) showed a glucose-raising effect, whereas it had a glucose-lowering effect at Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 kb) affecting body weight was identified. Experimental data from subcongenics supported the four loci. Sorcs1, one of the two known diabetes susceptibility genes in the region, resides within Niddm1i3, while Tcf7l2 maps outside all four loci. Multiple-marker QTL analysis incorporating the effect of cosegregating QTL as cofactors together with genetically selected progeny can remarkably enhance resolution of QTL. The data demonstrate that the species-conserved Niddm1i is a composite of at least four QTL affecting type 2 diabetes susceptibility and that two adjacent QTL (Niddm1i2GK and Niddm1i3GK) act in opposite directions.



Disease Annotations    

Phenotype Annotations    

Objects Annotated

QTLs
Bw123  (Body weight QTL 123)
Niddm64  (Non-insulin dependent diabetes mellitus QTL 64)
Niddm65  (Non-insulin dependent diabetes mellitus QTL 65)
Niddm66  (Non-insulin dependent diabetes mellitus QTL 66)

Objects referenced in this article
Marker D1Swe6 D1Swe6 Rattus norvegicus
Marker D1Swe1 D1Swe1 Rattus norvegicus
Marker D1Swe2 D1Swe2 Rattus norvegicus
Marker D1Swe4 D1Swe4 Rattus norvegicus
Marker D1Swe3 D1Swe3 Rattus norvegicus
Marker D1Swe8 D1Swe8 Rattus norvegicus
Marker D1Swe7 D1Swe7 Rattus norvegicus
Marker D1Swe5 D1Swe5 Rattus norvegicus
Strain F344.GK-(D1Mgh14-D1Rat90)/Swe null Rattus norvegicus
Strain F344/NCrl null Rattus norvegicus
Strain GK/KyoSwe Goto Kakizaki Rattus norvegicus
QTL Niddm35 Non-insulin dependent diabetes mellitus QTL 35 Rattus norvegicus

Additional Information