Affymetrix Microarray Validation of Qatari Exome Predicted Deleterious SNPs in Genes Linked to Human Health, but a Different SNP than Previously Reported1.

1Analysis of the exomes in the QE7 14 alleles identified 650 missense coding SNPs where the gene has been previously identified as linked to human health, but the missense SNP is different than that previously reported (Table 1, row 3). To validate this observation in a larger group of Qataris, the Affymetrix Genome-Wide SNP array 5.0 was used to assess an independent group of 149 Qataris (QA149, 298 alleles). Of the 2,750 missense potentially deleterious SNPs identified in at least 1 of the QE7 14 alleles, 131 were on the microarray. Of these, 49 were in genes linked to human health, including 33 where the gene is linked to human health, but the reported link was for a different SNP. Of these 33, listed are 10 chosen as examples of missense SNPs linked to human health that are extensively documented in the OMIM database (3).2Gene symbol and name obtained from the Consensus Coding Sequence (CCDS) NCBI database [32], amino acid substitution position and residues obtained from dbSNP when available; otherwise SIFT online webserver [34]. Transcript position and amino acid substitution was verified to be consistent with the literature.3SNP information includes amino acid substitution, dbSNP build 134 rsID if available, chromosome, position in GRCh37 human reference genome assembly, reference and alternate allele in QE7. Ref = references; alt = alternative.4Phenotype information from OMIM [12], HGMD [37], PharmGKB [38] or HUGE [39] database.5See Details S1.6Shown is the alternate allele frequency determined by exome sequencing in QE7 individuals.7Shown is the alternate allele frequency in the validation set of QA149 individuals (n = 149 Qatari, 298 alleles). Failed genotypes are accounted for in the allele frequency. For statistical comparisons of the QE7 and QA149 allele frequencies, see Figure 2.