| 1. |
- Edvardsen, Hege, et al.
(författare)
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Experimental validation of data mined single nucleotide polymorphisms from several databases and consecutive dbSNP builds
- 2006
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Ingår i: Pharmacogenetics & Genomics. - : Ovid Technologies (Wolters Kluwer Health). - 1744-6872 .- 1744-6880. ; 16:3, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- Rapid development in the annotation of human genetic variation has increased the numbers of single nucleotide polymorphisms (SNPs) in candidate genes by several orders of magnitude. The selection of both useful target SNPs; for disease-gene association studies and SNPs associated with the treatment response is therefore an increasingly challenging task. We describe a workflow for selecting SNPs based on their putative function and frequency in candidate genes extracted from PubMed resources. The annotation of each SNP and its frequency in a Caucasian population was assessed in several databases. Approximately 4000 SNPs were identified from an initial 233 candidate genes. In a case study, we performed actual genotyping of 1030 of these SNPs in 213 genes and obtained 710 successfully genotyped SNPs. Using the flow-chart outlined here, only 87 SNPs were monomorphic (approximately 12%). This study reports the frequency of SNPs in a Caucasian population, selected in silico, using a candidate gene approach and validated by actually genotyping 193 individuals. The selected genotypes represent a valuable set of verified candidate SNPs for pharmacogenetic studies in Caucasian populations.
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| 2. |
- Kristensen, Vessela N, et al.
(författare)
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Genetic variation in putative regulatory loci controlling gene expression in breast cancer
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:20, s. 7735-7740
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Candidate single-nucleotide polymorphisms (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 pathway. We describe a general statistical framework for the simultaneous analysis of gene expression data and SNP genotype data measured for the same cohort, which revealed significant associations between subsets of SNPs and transcripts, shedding light on the underlying biology. We identified SNPs in EGF, IL1A, MAPK8, XPC, SOD2, and ALOX12 that are 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. 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 with the same set of SNPs or to a single SNP were shown to be functionally coherent in Gene Ontology and pathway analyses and coexpressed in other independent data sets, suggesting that many of the observed associations are within the same functional pathways. To our knowledge, this article is the first study to correlate SNP genotype data in the germ line with somatic gene expression data in breast tumors. It provides the statistical framework for further genotype expression correlation studies in cancer data sets.
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| 3. |
- Nordgard, Silje H, et al.
(författare)
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Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients
- 2008
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47:8, s. 680-696
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Tidskriftsartikel (refereegranskat)abstract
- Breast carcinomas are characterized by DNA copy number alterations (CNAs) with biological and clinical significance. This explorative study integrated CNA, expression, and germline genotype data of 112 early-stage breast cancer patients. Recurrent CNAs differed substantially between tumor subtypes classified according to expression pattern. Deletion of 16q was overrepresented in Luminal A, and a predictor of good prognosis, both overall and for the nonluminal A subgroups. The deleted region most significantly associated with survival mapped to 16q22.2, harboring the genes TXNL4B and DXH38, whose expression was strongly correlated with the deletion. The area most frequently deleted resided on 16q23.1, 3.5 MB downstream of the area most significantly associated with survival, and included the tumor suppressor gene ADAMTS18 and the cell recognition gene CNTNAP4. Whole-genome association analysis identified germline single nucleotide polymorphisms (SNPs) and their corresponding haplotypes, residing on several different chromosomes, to be associated with deletion of 16q. The genes where these SNPs reside encode proteins involved in the extracellular matrix (CHST3 and SPOCK2), in regulation of the cell cycle (JMY, PTPRN2, and Cwf19L2) and chromosome stability (KPNB1).
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