The power, over and over again. I must admit that I am thoroughly confused by power calculations for rare genetic variants, particularly for de novo variants that are identified through trio exome sequencing. Carolien has recently written a post about the results we can expect from exome sequencing studies. For a current grant proposal, I have now tried to estimate the rate of de novos using a small simulation experiment. And I have realized that we need to re-think the concept of power. Continue reading
Tag Archives: whole exome sequencing
A new spectrum unfolding – KCNT1 mutations in ADNFLE and MMPSI
A surprising finding. The genetic basis of many epileptic encephalopathies and familial epilepsies remains unknown. Novel sequencing technologies such as Next Generation Sequencing now offer the possibility to identify the genetic basis of these conditions. However, it is a rare event that a single gene is implicated in two completely different epilepsy subtypes. Such a finding has now been reported in Nature Genetics. The KCNT1 gene is found to be mutated in Malignant Migrating Partial Seizures of Infancy (MMPSI) and a severe form of Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE). I doublechecked at least three times whether both papers actually talk about the same gene. Continue reading
Epilepsy genes in noncoding RNA
Genome vs. exome sequencing. Can non-coding regions be skipped in the search for disease-causing variants? Is it worth to pay a higher price for sequencing the whole genome?
The sequencing company Complete Genomics (CGI) is already sounding the death knell for exome sequencing, arguing that the protein-coding genes cover only ~1% of the genome, while many loci identified by GWAS lie in the non-coding regions. CGI maintains that the price difference between whole-genome (WGS) and exome sequencing (ES) has become “less of an issue”. With declining sequencing prices, this will certainly be the case in the future – however, when multiplying the current added costs for WGS with the large numbers of cases and controls required for finding new hits in complex diseases, the proponents of ES have strong arguments. Will WGS explain more than the 10% expected for exome sequencing? Continue reading
