Genome-wide linkage analysis in Spanish melanoma-prone families [Round1]
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PROVIDER: PRJNA430109 | ENA |
REPOSITORIES: ENA
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Project description:The main genetic factors for familial melanoma remain unknown in more than 75% of families. CDKN2A is mutated in around 20% of melanoma-prone families. Other high-risk melanoma susceptibility genes explain less than 3% of families studied to date. We performed the first genome-wide linkage analysis in CDKN2A-negative Spanish melanoma-prone families to identify novel melanoma susceptibility loci. We included 68 individuals from 2, 3 and 6 families with 2, 3 and at least 4 melanoma cases. We detected a locus with significant linkage evidence at 11q14.1-q14.3, with a maximum het-TLOD of 3.449 (rs12285365:A>G), using evidence from multiple pedigrees. The genes contained by the subregion with the strongest linkage evidence were: DLG2, PRSS23, FZD4 and TMEM135. We also detected several regions with suggestive linkage evidence (TLOD>1.9) (1q, 6p, 7p, 11q, 12p, 13q) including the region previously detected in melanoma-prone families from Sweden at 3q29. The family specific analysis revealed three loci with suggestive linkage evidence for family #1: 1q31.1-q32.1 (max. TLOD 2.447), 6p24.3-p22.3 (max. TLOD 2.409) and 11q13.3-q21 (max. TLOD 2.654). Future next generation sequencing studies of these regions may allow the identification of new melanoma susceptibility genetic factors.
2019-01-01 | GSE109207 | GEO
Project description:The main genetic factors for familial melanoma remain unknown in more than 75% of families. CDKN2A is mutated in around 20% of melanoma-prone families. Other high-risk melanoma susceptibility genes explain less than 3% of families studied to date. We performed the first genome-wide linkage analysis in CDKN2A-negative Spanish melanoma-prone families to identify novel melanoma susceptibility loci. We included 68 individuals from 2, 3 and 6 families with 2, 3 and at least 4 melanoma cases. We detected a locus with significant linkage evidence at 11q14.1-q14.3, with a maximum het-TLOD of 3.449 (rs12285365:A>G), using evidence from multiple pedigrees. The genes contained by the subregion with the strongest linkage evidence were: DLG2, PRSS23, FZD4 and TMEM135. We also detected several regions with suggestive linkage evidence (TLOD>1.9) (1q, 6p, 7p, 11q, 12p, 13q) including the region previously detected in melanoma-prone families from Sweden at 3q29. The family specific analysis revealed three loci with suggestive linkage evidence for family #1: 1q31.1-q32.1 (max. TLOD 2.447), 6p24.3-p22.3 (max. TLOD 2.409) and 11q13.3-q21 (max. TLOD 2.654). Future next generation sequencing studies of these regions may allow the identification of new melanoma susceptibility genetic factors.
2019-01-01 | GSE109206 | GEO
Project description:Genome-wide linkage analysis in Spanish melanoma-prone families
| PRJNA430107 | ENA
Project description:Genome-wide linkage analysis in Spanish melanoma-prone families [Round2]
| PRJNA430108 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-01-01 | GSE109208 | GEO
Project description:The main genetic factors for familial melanoma remain unknown in >75% of families. CDKN2A is mutated in around 20% of melanoma-prone families. Other high-risk melanoma susceptibility genes explain <3% of families studied to date. We performed the first genome-wide linkage analysis in CDKN2A-negative Spanish melanoma-prone families to identify novel melanoma susceptibility loci. We included 68 individuals from 2, 3, and 6 families with 2, 3, and at least 4 melanoma cases. We detected a locus with significant linkage evidence at 11q14.1-q14.3, with a maximum het-TLOD of 3.449 (rs12285365:A>G), using evidence from multiple pedigrees. The genes contained by the subregion with the strongest linkage evidence were: DLG2, PRSS23, FZD4, and TMEM135. We also detected several regions with suggestive linkage evidence (TLOD >1.9) (1q, 6p, 7p, 11q, 12p, 13q) including the region previously detected in melanoma-prone families from Sweden at 3q29. The family-specific analysis revealed three loci with suggestive linkage evidence for family #1: 1q31.1-q32.1 (max. TLOD 2.447), 6p24.3-p22.3 (max. TLOD 2.409), and 11q13.3-q21 (max. TLOD 2.654). Future next-generation sequencing studies of these regions may allow the identification of new melanoma susceptibility genetic factors.
| S-EPMC6057984 | biostudies-literature
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.
2016-12-01 | GSE85010 | GEO
Project description:BACKGROUND:In the United States, only approximately 0.4% of all melanomas are diagnosed in patients aged <20 years. To the authors' knowledge, melanoma in pediatric members of melanoma-prone families has not been fully investigated to date. The objective of the current study was to evaluate pediatric patients with melanoma with extensive follow-up in melanoma-prone families with and without cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. METHODS:For this non-population-based study, families were followed prospectively for up to 40 years. A total of 60 families with???3 patients with melanoma were included for analysis: 30 CDKN2A mutation-positive (CDKN2A+) and 30 CDKN2A mutation-negative (CDKN2A-) families. Age at the time of first melanoma and number of melanomas were obtained for each patient and summarized by family or sets (CDKN2A?+?vs CDKN2A-). For set comparisons and categorical variables (occurrence of melanoma in pediatric patients, number of melanomas, number of patients with single or multiple melanomas), the Pearson chi-square or Fisher exact test was used. RESULTS:Regardless of CDKN2A status, melanoma-prone families were found to have 6-fold to 28-fold higher percentages of patients with pediatric melanoma compared with the general population of patients with melanoma in the United States. Within CDKN2A?+?families, pediatric patients with melanoma were significantly more likely to have multiple melanomas compared with their relatives who were diagnosed at age >20 years (71% vs 38%, respectively; P?=?.004). CDKN2A?+?families had significantly higher percentages of pediatric patients with melanoma compared with CDKN2A- families (11.1% vs 2.5%; P?=?.004). CONCLUSIONS:These observations have implications for the prevention of melanoma as well as clinical care for its early detection. Children in melanoma-prone families should have careful sun protection from an early age and skin surveillance to reduce their risk of melanoma.
| S-EPMC6214720 | biostudies-literature
Project description:Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with = 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. Keywords: Autism spectrum disorder, Affymetrix SNP genotyping, linkage analysis, copy number analysis, chromosomal rearrangements.
2007-02-20 | GSE6754 | GEO