Whilst both techniques have been used for some years now on a research basis for the investigation of suspected genetic diseases in patients for whom no other diagnosis was available, routine clinical sequencing of this kind is relatively new.
First made available in the US in 2011 for under $10,000, new providers are joining the market; those associated with academic institutions can contribute their anonymised data to public databases to support further research.
Deciding which sequence variants may cause disease is much more complex than the sequencing itself; checking against the corresponding sections of parental genomes can confirm that the variants are not inherited, and identifying changes within genes already known to be associated with disease can provide further clues, but answers are rarely definitive. However, as research databases expand, the evidence to inform analysis is slowly accumulating.
Meanwhile, researchers have devised a compromise: a kit designed to allow targeted sequencing of 5,000 ‘medically relevant’ genes. This ensures deeper coverage of these key genomic regions – including those that may not be reliably sequenced by current exome sequencing kits - reducing costs by missing out other areas less likely to be of interest; it is expected that the precise regions will vary over time as new knowledge emerges.
Initiatives of this kind will be of great interest to other countries considering how best whole genome and exome sequencing may be incorporated into routine clinical investigation of certain conditions, such as learning disability and developmental delay of unknown cause.