A group of researchers led by Timothy Aitman of the MRC Clinical Sciences Centre and Imperial College London used the SHR (spontaneously hypertensive rat) to identify the few genes they thought predisposed this strain to hypertension (several genes had already been identified but the group knew or felt a few others remained to be discovered). Sequencing this SHR rat with the NextGen approach and comparing those data to the rat reference genome, led to quite a surprise. 788 genes are mutated in SHR compared to the reference genome, including 60 that are deleted altogether.
My take on this is many genes are likely involved in a complex disorder and many genes - with specific variants - may work in concert to produce the disease phenotype – either via gene-gene interactions or affecting interconnecting pathways.
This type of result is very likely to be repeated with other metabolically sensitive disorders and afflictions such as dyslipidemia, obesity and type 2 diabetes. A series of variations in genes combined with deviations from a standard environment - both in terms of diet and microbiome - are likely to combine to tip the balance and enhance onset and/or progression of said affliction.
ReferenceThe genome sequence of the spontaneously hypertensive rat: Analysis and functional significance. Genome Res. (in press).