Next-generation sequencing improves molecular epidemiological characterization of thalassemia in Chenzhou Region, P.R. China

J Clin Lab Anal. 2019 May;33(4):e22845. doi: 10.1002/jcla.22845. Epub 2019 Feb 27.

Abstract

Objectives: Thalassemia is a highly prevalent monogenic inherited disease in southern China. It is important to collect epidemiological data comprehensively for proper prevention and treatment.

Methods: In this study, blood samples collected from 15 807 residents of Chenzhou were primarily screened by hematological tests. A total of 3973 samples of suspected thalassemia carriers were further characterized by combined next-generation sequencing (NGS) and Gap-PCR.

Results: In total, 1704 subjects were diagnosed as thalassemia carriers with a total prevalence rate of 10.78%, including 943 α-thalassemia carriers, 708 β-thalassemia carriers, and 53 composite α and β-thalassemia carriers. The prevalence rates of α-thalassemia, β-thalassemia, and composite α and β-thalassemia were 5.97%, 4.48%, and 0.34%, respectively. Meanwhile, we characterized 19 α-thalassemia variations and 21 β-thalassemia variations in thalassemia carriers. Approximately 2.88% of thalassemia carriers would be missed by traditional genetic analysis. In addition, four novel thalassemia mutations and one novel abnormal hemoglobin mutation were identified.

Conclusions: Our data suggest a high prevalence of thalassemia and a diverse spectrum of thalassemia-associated variations in Chenzhou. Also, combined NGS and Gap-PCR is an effective thalassemia screening method. Our findings might be helpful for prevention and treatment of thalassemia in this region.

Keywords: mutation; next-generation sequencing; prevalence; thalassemia; variant.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • China / epidemiology
  • Female
  • Genetic Carrier Screening
  • Hemoglobins, Abnormal / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Molecular Epidemiology
  • Mutation
  • Polymerase Chain Reaction / methods
  • Young Adult
  • alpha-Thalassemia / epidemiology*
  • alpha-Thalassemia / genetics*
  • beta-Thalassemia / epidemiology*
  • beta-Thalassemia / genetics*

Substances

  • Hemoglobins, Abnormal