Prediction of cis-QTLs in a pair of inbred mouse strains with the use of expression and haplotype data from public databases
Cis-QTLs are important candidates for any other trait that maps to the same locus. In this article we have used publicly available databases and a small microarray data set to “map” cis-QTLs in the ILS and ISS inbred mouse strains without the need to generate microarray data from an ILSXISS segregating population. Expression data were obtained from brains of C57BL/6, DBA/2, ILS, and ISS. Cis-QTLs were mapped for the 760 transcripts found to be differentially expressed between the C57BL/6 and DBA/2 using expression data previously obtained from the BXD RIs. The 469 detected cis-QTLs were then examined for SNP haplotypes and expression patterns that could relate the ILS and ISS to the C57BL/6 and DBA/2. Of the 338 cis-QTL transcripts that had informative haplotypes, 189 were significantly different between the ILS and ISS with 184 showing segregation of haplotype with expression. These were considered to be probable cis-QTLs in the ILS and ISS. There were almost certainly additional ILS/ISS cis-QTLs among the other transcripts with informative haplotypes, but in the absence of an ILS/ISS expression difference, the level of confidence was reduced. Several of the putative ILS/ISS cis-QTLs are considered important candidate genes because they are linked to ILS/ISS behavioral QTLs. A potential ascertainment bias related to strain-dependent target sequences was observed suggesting that as much as 35% of the cis-QTLs were hybridization artifacts. Nonetheless, the results suggest that this approach is an economical and widely applicable method for mapping cis-QTLs in a strain pair of interest.
KeywordsInbred Strain Recombinant Inbred Inbred Mouse Strain Recombinant Inbred Strain Strain Pair
The authors thank Ms. Lashell Lintz and Ms. Kathryn Zolman for their expert technical help and the UCDHSC Affymetrix core facility for support and advice. This work was supported by NIH grants R01-AA13177 (R.A. Radcliffe), U01-AA13499 (R.W. Williams), and P20-DA21131 (R.W. Williams).
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