Project description:Digital dermatitis (DD) causes lameness in dairy cattle. To detect quantitative trait loci (QTL) associated with DD, genome-wide association studies (GWAS) were performed using high density single nucleotide polymorphism (SNP) genotypes and binary case/control, quantitative (average number of FW per hoof trimming record), and recurrent (cases with 2 DD episodes vs. controls) phenotypes from cows across four dairies (controls n = 129 vs. FW n = 85). Linear mixed model (LMM) and random forest (RF) approaches identified top SNPs, which were used as predictors in Bayesian regression models to assess SNP predictive value. The LMM and RF analyses identified a QTL on BTA1 for the binary phenotype and on BTA2 for the quantitative phenotype. The binary and recurrent LMM GWASs also detected a QTL on BTA2 that was at a different position than the QTL from the quantitative phenotype analysis. The QTL on BTA1 lacked apparent candidate genes, whereas both QTL on BTA2 included genes associated with immune response and wound healing. Although larger sample sizes are necessary to reaffirm these small effect loci amidst a strong environmental effect, the sample cohort used in this study was sufficient for estimating SNP effects with high predictive value.
Project description:We applied Illumina’s 317K high-density SNP-arrays to profile chromosomal aberrations in clear cell renal cell carcinoma (ccRCC) from 80 patients and analyzed the association of LOH/amplification events with clinicopathological characteristics
Project description:Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and SNP arrays to characterize CNVs in 335 individuals (240 melanoma cases) from American melanoma-prone families (22 with germline CDKN2A or CDK4 mutations). We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g. PARP1, CDKN2A) or co-segregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare co-segregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma.
Project description:Karyotyping by SNP array of primary uveal melanoma samples, uveal melanoma cell lines and normal controls The Human660WQuad v1.0 DNA Analysis Bead Chip and kit were used for high resolution molecular karyotyping of DNA isolated from snap-frozen primary uveal melanoma tissue isolated from enucleated eyes.
Project description:Metastatic melanoma is an aggressive treatment-refractory malignancy. Recently, c-Kit mutations were discovered in certain mucosal melanomas. A clinical trial was initiated with the c-Kit inhibitor imatinib mesylate. The first treated patient experienced dramatic clinical improvement within days, followed by major responses by PET/CT four weeks later at all sites of metastatic disease. Several established mucosal melanoma cell lines exhibited imatinib sensitivity in a fashion correlating with c-Kit mutational status. Although c-Kit mutations are uncommon in cutaneous melanoma, they may arise in geographically distinct subsets for whom use of c-Kit targeted kinase inhibition should be considered in a rational therapeutic approach. Keywords: Whole genome copy number analysis Copy number analysis using high-density SNP arrays to investigate genetic gains and losses involved in the genesis of mucosal and cutaneous melanoma. GSE8164_raw_copy_number_calls.xls contains raw copy number calls generated by dChip (build 5/2007) for GIST, K008, K029, M34, MEL1, MEL40, M6, and 5 Affymetrix controls (copy number identity 2 i.e. normal), which are available on the HapMAP site.
Project description:We applied Illuminaâs 317K high-density SNP-arrays to profile chromosomal aberrations in clear cell renal cell carcinoma (ccRCC) from 80 patients and analyzed the association of LOH/amplification events with clinicopathological characteristics Log_R_Ratio and differece of Allele frequency were calculated by comparing the tumor sample to reference DNA, which is from the peripheral blood of corresponding patient
