Genetic variation in the MAPK/ERK pathway affects contact hypersensitivity responses

Using a genetic resource that enables rapid mapping of genes for complex traits, we demonstrate dramatic diversity between murine strains in response to immune challenge. We identified several candidate genes that point to the MAPK/ERK pathway as a key modulator of this process

The Affymetrix DMET Plus Platform Reveals Unique Distribution of ADME-Related Variants in Ethnic Arabs

Background. The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s), the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among individuals, but also between ethnic populations. Materials and Methods. We genotyped 600 Saudi individuals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs. Results. Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs) than those in other ethnic groups. Discussion. The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population

Data on common variants associated with coronary artery disease/myocardial infarction in ethnic Arabs

The data shows results acquired in a large cohort of 5668 ethnic Arabs involved in a common variants association study for coronary artery disease (CAD) and myocardial infarction (MI) using the Affymetrix Axiom Genotyping platform (“A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs” Wakil et al. (2015) [1] ). Several loci were described that conferred risk for CAD or MI, some of which were validated in an independent set of samples. Principal Component (PCA) analysis suggested that the Saudi Cohort was close to the CEU and TSI populations, thus pointing to similarity with European populations

A New Susceptibility Locus for Myocardial Infarction, Hypertension, Type 2 Diabetes Mellitus, and Dyslipidemia on Chromosome 12q24

We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820_CC (1.19 (1.01–1.42); P=0.041), rs2464196_TT (1.19 (1.00–1.40); P=0.045), and rs2259816_T (1.13 (1.01–1.26); P=0.031) were associated with MI. The rs2259820_T (1.14 (1.03–1.26); P=0.011) and rs2464196_C (1.12 (1.02–1.24); P=0.024) were associated with type 2 diabetes mellitus (T2DM), while the rs2393791_T (1.14 (1.01–1.28); P=0.032), rs7310409_G (1.16 (1.03–1.30); P=0.013), and rs2464196_AG+GG (1.25 (1.05–1.49); P=0.012) were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791_T (1.14 (1.02–1.27); P=0.018), rs7310409_G (1.12 (1.01–1.25); P=0.031), rs1169310_G (1.15 (1.04–1.28); P=0.010), and rs1169313_CT+TT (1.24 (1.06–1.45); P=0.008) and high low density lipoprotein-cholesterol levels were associated with rs2259820_T (1.23 (1.07–1.41); P=0.004), rs2464196_T (1.22 (1.06–1.39); P=0.004), and rs2259816_T (1.18 (1.02–1.36); P=0.023). A 7-mer haplotype CATATAC (χ2=7.50; P=0.0062), constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (χ2=3.94; P=0.047). Hypertriglyceridemia was linked to TGCGGG (χ2=4.26; P=0.039), and obesity to ACGGGT (χ2=5.04; P=0.025). Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia

Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection

Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS) platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a result, these technologies have become a valuable tool for gene discovery and for clinical diagnostics. The AmpliSeq Inherited Disease Panel (IDP) consists of 328 genes underlying more than 700 inherited diseases. Here, we aimed to assess the performance of the IDP as a sensitive and rapid comprehensive gene panel testing. A total of 88 patients with inherited diseases and causal mutations that were previously identified by Sanger sequencing were randomly selected for assessing the performance of the IDP. The IDP successfully detected 93.1% of the mutations in our validation cohort, achieving high overall gene coverage (98%). The sensitivity for detecting single nucleotide variants (SNVs) and short Indels was 97.3% and 69.2%, respectively. IDP, when coupled with Ion Torrent Personal Genome Machine (PGM), delivers comprehensive and rapid sequencing for genes that are responsible for various inherited diseases. Our validation results suggest the suitability of this panel for use as a first-line screening test after applying the necessary clinical validation