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.
Radcliffe
Richard A
RA
Department of Pharmaceutical Sciences, University of Colorado at Denver and Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA. Richard.Radcliffe@UCHSC.edu
Lee
Michael J
MJ
Williams
Robert W
RW
D000818:Animals; D002874:Chromosome Mapping; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D006239:Haplotypes; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011237:Predictive Value of Tests; D040641:Quantitative Trait Loci