In the ExAC database, only seven individuals have been documented with a PPP1R15B loss-of-function variant, none of which are homozygous and residue 658 has only one documented heterozygous variant in one individual, p.R658H.
Apart from a weak association (p = 0.04) for the NEGR1 variant, none of the other variants (in or near SEC16B, BDNF, SH2B1, MC4R and KCTD15) studied by Thorleifsson et al. showed association with the risk of type 2 diabetes.
I was duly informed that I had several variants — none of them particularly rare — in TAS2R38 and TAS2R13, two of the genes that encode for the taste receptors that perceive bitterness.
Due to the low minor allele frequencies of the rare variants, none of the p-values is smaller than 0.001.
While TCGA performed Sanger validation of a small subset of their variants, none of the variants validated by Veridical had any associated Sanger sequencing data.
Even if there exists a large number of methods for analyzing rare variants, none of those has been tailored for multivariate phenotypes.
Additionally, while 67.3% and 66.2% of PPVs in the BRCA1 and BRCA2 genes in the BRCA1/2 cohort, respectively, were predicted LoF variants, none of the four BRCA1 or 16 BRCA2 variants in the non-BRCA cohort were predicted LoF variants.
While we identified 231 differences (216 from the LCL, 15 from the genomic DNA) in single nucleotide variants, none of the 60 randomly selected variants validated by Sanger sequencing.
In contrast, among cDNAs from golden fish of the MAC and BDZW1 backgrounds, we found a total of six different kita splice variants, none of which was wild type.
In addition, GWAS and population-genetic data now frequently contain genotype likelihoods, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format.
As experience with the method progresses and prices drop, these limitations will be offset by the advantages of superior dynamic range, the discovery of novel transcripts, and the simultaneous assessment of expression levels, sequence variants and splice variants, none of which can be achieved using conventional probe-based transcript analysis.
