Dac ID Contact Person Email Access Information
EGAC00001000259 Kathleen Stirrups nihr_dac [at] medschl [dot] cam [dot] ac [dot] uk No additional information is available

This DAC controls 7 datasets:

Dataset ID Description Technology Samples
EGAD00001001333 Whole exome sequencing BAM files for samples from the BRIDGE Consortium with pathogenic or likely pathogenic variants on genes linked to bleeding or platelet disorders. Illumina HiSeq 2000 28
EGAD00001002656 Whole exome sequencing BAM files and whole genome sequencing CRAM files for 722 individuals from the NIHR-BioResource Rare Diseases Consortium (SPEED project) with inherited retinal disease. Illumina HiSeq 2000 767
EGAD00001002730 SPEED - childhood dystonia KMT2B dataset Illumina HiSeq 2000 5
EGAD00001003423 Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within genes encoding components of the transforming growth factor-ß pathway underlie the majority of heritable forms of PAH. Identifying the missing genetic contribution is challenging, even with genes of large effect size, since it likely involves mutations in genes confined to small numbers of PAH cases. In this study, we performed whole genome sequencing, comparing 1038 PAH index cases to 6385 subjects with other rare diseases. Rare variant analysis identified mutations in novel causal genes, namely ATP13A3, AQP1 and SOX17, and provided independent validation of a critical role for GDF2 in PAH. We detected mutations predicted to be disruptive of function in most, but not all, previously reported PAH genes. Taken together these findings provide new insights into the molecular basis of PAH, and support a central role for endothelial dysregulation in disease pathogenesis. Illumina HiSeq 2000 371
EGAD00001004088 Multiple primary tumors (MPT) affect a substantial proportion of cancer survivors and may result from various causes including inherited predisposition. Currently, germline genetic testing of MPT cases for cancer predisposition gene (CPG) variants is mostly targeted by tumor type. We ascertained pre-assessed MPT cases from genetics centers (defined as ≥2 primaries by age 60 years or ≥3 by 70) and performed whole genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment/molecular investigations, pathogenic variants in moderate and high-risk CPGs were detected in 67/440 (15.2%) of probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies including structural variants at low frequency (6/440 (1.4%) of probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant) the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice site CPG variants and at least one discordant tumor type was significantly higher than a control population (χ2=43.642 P=<0.0001). 2/67 (3%) of probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Summing together variant detection rates from a similarly ascertained previous MPT case series, the present results suggest that first-line comprehensive CPG analysis in a clinical genetics referral-based MPT cohort would detect a deleterious variant in about a third of cases. Illumina HiSeq 2000 453
EGAD00001004089 SRNS unknown Illumina HiSeq 2000 4
EGAD00001004438 This dataset contains short-read WGS data of four individuals with complex structural variants from the NIHR Bioresource project. Illumina HiSeq 2000 4