Haplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.

ABSTRACT: Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci. The highly homologous regions of α-/β-globin gene clusters are then phased and 3 novel haplotypes in HBG1/HBG2 region are reported in this population of β-thalassemia patients. Furthermore, one of the haplotypes is associated with ameliorated symptoms of β-thalas

SUBMITTER: Ye Y 

PROVIDER: S-EPMC11884621 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature