The Thai reference exome (T‐REx) variant database

Abstract

To maximize the potential of genomics in medicine, it is essential to establish databases of genomic variants for ethno‐geographic groups that can be used for filtering and prioritizing candidate pathogenic variants. Populations with non‐European ancestry are poorly represented among current genomic variant databases. Here, we report the first high‐density survey of genomic variants for the Thai population, the Thai Reference Exome (T‐REx) variant database. T‐REx comprises exome sequencing data of 1092 unrelated Thai individuals. The targeted exome regions common among four capture platforms cover 30.04 Mbp on autosomes and chromosome X. 345 681 short variants (18.27% of which are novel) and 34 907 copy number variations were found. Principal component analysis on 38 469 single nucleotide variants present worldwide showed that the Thai population is most genetically similar to East and Southeast Asian populations. Moreover, unsupervised clustering revealed six Thai subpopulations consistent with the evidence of gene flow from neighboring populations. The prevalence of common pathogenic variants in T‐REx was investigated in detail, which revealed subpopulation‐specific patterns, in particular variants associated with erythrocyte disorders such as the HbE variant in HBB and the Viangchan variant in G6PD. T‐REx serves as a pivotal addition to the current databases for genomic medicine.

Genotypic and phenotypic landscapes of 51 pharmacogenes derived from whole-genome sequencing in a Thai population

“…Our study recruited healthy parents of children with rare diseases; thus, more prevalent pathogenic variants for rare diseases are expected, as observed in the Thai Reference Exome (T-REx) Database with similar inclusion criteria [ 76 ]. T-REx recruited unaffected parents of children with rare diseases and found a more enriched pathogenic variants, compared with gnomAD.…”

Genetic basis of sudden death after COVID-19 vaccination in Thailand

“…Postmortem blood was obtained for genomic DNA extraction; then, whole exome sequencing (WES) was performed as described previously. 5 Briefly, the sequencing libraries were enriched using a SureSelect Human All Exon V7 kit Q6 and were sequenced using Illumina HiSeq 4000. The only unequivocal, major genetic locus responsible for Brugada syndrome (BrS) is SCN5A-SCN10A, 6,7 and its common variants could have susceptible effects on the phenotype.…”

A LILRB1 variant with a decreased ability to phosphorylate SHP-1 leads to autoimmune diseases

“…S1a-1c ). WES with filtering steps (Supplementary Table S2 ) revealed three non-synonymous exonic variants present in all nine patients with allele frequencies < 1% in public and in-house databases 11 (Supplementary Table S3 ). Remarkably, only one variant was located on the chromosomal linked region, which was a heterozygous missense mutation in LILRB1 (hg19; chr19:55,143,506; c.479G > A; p.Gly160Glu; rs866926837).…”

“…A LILRB1 variant with a decreased ability to phosphorylate SHP-1 leads to autoimmune diseases Thivaratana Sinthuwiwat 1,2,3,4 , Supranee Buranapraditkun 5,6,7 , Wuttichart Kamolvisit 2,3 , Siraprapa Tongkobpetch 2,3 , Wanna Chetruengchai 1,2,3 , Chalurmpon Srichomthong 2,3 , Adjima Assawapitaksakul 2,3 , Chureerat Phokaew 2,3,8 , Patipark Kueanjinda 9,10 , Tanapat Palaga 10,11 , Tadech Boonpiyathad 12 , Kanya Suphapeetiporn 2,3 , Nattiya Hirankarn 9,10 & Vorasuk Shotelersuk 2,3* Inborn errors of immunity are known to cause not only immunodeficiencies and allergies but also autoimmunity. Leukocyte immunoglobulin-like receptor B1 (LILRB1) is a receptor on leukocytes playing a role in regulating immune responses.…”