The gene expression in each tissue, healthy or malignant, may have its inherited genetic component which differs from individual to individual. The first evidence for this is brought by this recent publication of Kristensen et al. where SNP (single nucleotide polymorphisms, single base variants in the DNA) data in the germline were correlated with somatic gene expression data in breast tumors.
Candidate SNPs were analyzed for associations to an unselected whole genome pool of tumor mRNA transcripts in 50 unrelated patients with breast cancer. SNPs were selected from 203 candidate genes of the reactive oxygen species (ROS) pathway. Every gene has up to hundreds of SNPs, dependent on the size and degree of conservation.
A general statistical framework was developed for the simultaneous analysis of gene expression data and SNP genotype data measured for the same cohort. It revealed significant associations between subsets of SNPs and transcripts, shedding light on the underlying biology. SNPs in important regulators such as EGF, IL1A, MAPK8, XPC, SOD2 and ALOX12 were associated with the expression patterns of a significant number of transcripts, indicating the presence of regulatory SNPs in these genes. SNPs were found to act in-trans in a total of 115 genes. Of these, SNPs in 43 of these 115 genes were found to act both in-cis and in-trans.
Finally, subsets of SNPs that share significantly many common associations with a set of transcripts (biclusters) were identified. The subsets of transcripts that are significantly associated to the same set of SNPs or to a single SNP were shown to be functionally coherent in GO and pathway analyses and co-expressed in other independent data sets, suggesting that many of the observed associations are within the same functional pathways
Kristensen VN, Edvardsen H, Tsalenko A, Nordgard SH, Sorlie T, Sharan R, Vailaya A, Ben-Dor A, Lonning PE, Lien S, Omholt S, Syvanen AC, Yakhini Z, Borresen-Dale AL.
Genetic variation in putative regulatory loci controlling gene expression in breast cancer.
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7735-40. Epub 2006 May 9.
The home page of Vessela N. Kristensen's group: Cancer Genome Variation ( radium.no/kristensen )
Department of GeneticsInstitute for Cancer Research