Analysis of family-based whole-genome sequence data

Data are rapidly accumulating that rare variants have a large cumulative effect on normal phenotypic variation and are extremely important to disease. Pedigree-based studies represent an implicit enrichment strategy for identifying such rare variants. Mendelian transmissions from parents to offspring maximize the chance that multiple copies of rare variants exist in the pedigree. Only in pedigrees is it possible to capture sufficient numbers of private functional variants to permit discovery. Additionally, for rare but non-private variants, extended pedigrees lead to substantially increased variance in allele frequency which permits a much wider potential for large genetic signals. Pedigree-based comprehensive deep sequencing projects, particularly those originally focused on previously localised QTL regions, should lead to rapid causal gene/variant identification.

We have next-generation whole genome sequence data from extended pedigrees for diseases include glaucoma and various cancers. Identifying the exact causal sequence variants that correlates with disease risk is difficult and represents one of the main challenges of modern human genetics.

Project tasks: Analyse pedigree-based whole genome sequencing data to identify disease causing variation. These analyses will require research into the leading edge of current bioinformatics and computational genetic methodologies.
Once all potential variants have been identified bioinformatics and systems biology approaches will be required to determine which variants are likely to contribute to disease.

Research Groups


Team Leaders

  • Dr Jac Charlesworth (Research Fellow)