From a more methodological perspective, this work suggests that our study design, able to provide complementary information on linkage and association in three isolated populations with similar common genetic variations but possibly divergent rarer variations, is particularly powerful in a discrimination between causal and non causal variants.
Identification of these rarer variations in coding regions is now feasible and cost effective through exome sequencing, which has already identified high-penetrance variants for some rare diseases.
However, the sample sizes for any given population range from 61 to 113 individuals, limiting detection of rarer variation.
Thus, in large societies, many individuals can carry the rarer version of the single letter variation in their DNA sequence.Researchers trying to discover the genes that make some people susceptible to certain diseases compare a group of sick people with a group of healthy ones.
We searched for changes induced by NaAzide, which compared to changes derived from natural variation represent a considerable challenge because they are much rarer than variation SNP [ 1, 15].
Together with the WFS1 study, our results have a number of implications for the study of rarer genetic variation in diabetes.
A much rarer, and happier, variation on surprise at how many series a programme has had was experienced by Line of Duty, still the standout drama of this year.
Therefore, there is much interest in accounting for the missing heritability, and possible sources include loss of information through ignoring phenotype heterogeneity (disease subtypes have genetic differences), gene gene and gene environment interaction, and rarer forms of variation.
In the meantime, analysis of breast cancer exomes to identify SNPs and insertion deletion polymorphisms will provide important insights by providing the first opportunity to examine rarer forms of variation in coding regions.
It is still some way off the roughly 80% we would expect from twin, family and adoption studies, but this is likely to be because there are other kinds of genetic variation, and rarer genetic variants, not captured by this method, and still to be discovered.
Here, we describe development of this method and its application for discovery and detection of Single Nucleotide Polymorphisms (SNP) induced by mutagenesis, a type of variation much rarer and thus more difficult to detect than natural SNP.
