The functional importance and detection of regulatory sequence variants|
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics - University of British Columbia, Vancouver BC, Canada
The convergence of high-throughput technologies for sequencing individual exomes and genomes and rapid advances in genome annotation are driving a neo-revolution in human genetics.
This wave of family-based genetics analysis is revealing causal mutations responsible for striking phenotypes. By mapping the reads to the human genome reference and by
searching for variations relative to the reference, a list of small nucleotide variations and structural variations is obtained. Analysis is required to reveal those variations
most likely to contribute to a disease phenotype within a family. Existing software such as SIFT and PolyPhen score the severity of changes that arise in protein encoding exons.
However, most mutations within a family are situated in the 98% of the genome that controls the developmental and physiological profile of gene activity - the sequences
that control when and where a gene will be active.