Recent GWAS studies have been successful in identifying many low-penetrant susceptibility alleles for prostate cancer, and it is anticipated that many more variants will be detected through combined analysis across existing studies, new generations of larger studies, and increasing size of replication studies.
Many novel variants will be discovered from exome and genome sequencing.
Since many missense variants will not significantly impact protein function (92, 93), a second analysis might focus on the subset of these variants that are predicted to have deleterious consequences.
It could be argued that since SNP calling is conservative, many rare variants will have been missed, possibly leading to an artificially high Tajima's D statistic for the region.
In practice, decades of research have shown that this is highly unlikely to happen, and many causal variants will remain undiscovered even in the largest GWAS (genome-wide association studies) experiments [ 35] as shown in Figures 5 and 6.
It is expected that many rare variants will have a very restricted geographic distribution (51, 52) so that careful matching of case and control ancestries is likely to be extremely important.
ChRs will be further optimized for two-photon microscopy and many novel unprecedented variants will be identified.
This shows that as for nuclear genes the recent European population growth has resulted in a large set of new variants within the last tens of generations and many of these variants will be specific to the Danish population.
There is clear evidence for the involvement of several large, rare genomic copy number variants in schizophrenia, and it is likely that many more such variants will be implicated in the disorder over the coming years.
It appears likely that, in many instances, CDH1 variants will require the presence of other etiologic factors to increase disease risk, as E-cadherin deficiency is usually associated with cancer progression rather than initiation [ 41].
