RGD Reference Report - Fine-mapping a locus for glucose tolerance using heterogeneous stock rats. - Rat Genome Database

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Fine-mapping a locus for glucose tolerance using heterogeneous stock rats.

Authors: Solberg Woods, L  Holl, K  Tschannen, M  Valdar, W 
Citation: Solberg Woods L, etal., Physiol Genomics. 2010 Jan 12.
RGD ID: 2316693
Pubmed: PMID:20068026   (View Abstract at PubMed)
PMCID: PMC2841497   (View Article at PubMed Central)
DOI: DOI:10.1152/physiolgenomics.00178.2009   (Journal Full-text)

Heterogeneous stock (HS) animals provide the ability to map quantitative trait loci at high resolution (less than 5 Megabases) in a relatively short time period. In the current study, we hypothesized that the HS rat colony would be useful for fine-mapping a region on rat chromosome 1 that has previously been implicated in glucose regulation. We administered a glucose tolerance test to 515 HS rats and genotyped these animals with 69 microsatellite markers, spaced an average distance of less than one Megabase (Mb) apart, on a 67 Mb region of rat chromosome 1. Using regression modeling of inferred haplotypes based on a hidden Markov model reconstruction and mixed model analysis in which we accounted for the complex family structure of the HS, we identified one sharp peak within this region. Using positional bootstrapping, we determined the most likely location of this locus is from 205.04-207.48Mb. This work demonstrates the utility of HS rats for fine-mapping complex traits and emphasizes the importance of taking into account family structure when using highly recombinant populations. Key words: type 2 diabetes, quantitative trait loci, genetic maping, mixed model analysis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hyperglycemia  IDA 2316693 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
impaired glucose tolerance inducedIAGPglucose solution2316693; 2316693compared to BN/SsN more ...RGD 
increased circulating glucose level  IDA 2316693 RGD 
Objects Annotated

Gluco56  (Glucose level QTL 56)

ACI/Eur  (August x Copenhagen Irish)
NMcwi:HS  (Heterogeneous stock)
WKY/NHsd  (NA)

Objects referenced in this article
Strain ACI/N A X C 9935, Irish Rattus norvegicus
Strain WKY/N null Rattus norvegicus

Additional Information