Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality, China

Genet Med. 2017 Sep;19(9):1022-1031. doi: 10.1038/gim.2016.218. Epub 2017 Jan 26.

Abstract

Purpose: Thalassemia is one of the most common monogenic diseases in southwestern China, especially among the Dai ethnic group. Here, we explore the feasibility of a next-generation sequencing (NGS) screening method specifically for the Dai people.

Methods: Blood samples were obtained from Dai people for premarital screening. Double-blind, parallel hemoglobinopathy screening was conducted using both traditional hematological methods (red cell indexes and hemoglobin electrophoresis, then DNA sequencing) and an NGS approach.

Results: Among 951 tested individuals, we found a thalassemia carrier rate of 49.5% (471/951) using the NGS screen, in contrast to 22.0% (209/951) found using traditional methods. Almost 74.8% (217/290) of α-thalassemia carriers and 30.5% (25/82) of composite α- and β-thalassemia carriers were missed by traditional screens. The proportion of such α- and β-thalassemia carriers among the Dai people is 8.6% (82/951). For β-thalassemia carriers, the high ratio (66/99) of CD26 mutations may suggest a correlation between CD26 and the environmental adaption of the Dai people.

Conclusions: Methodological comparisons demonstrate the superiority of NGS for both sensitivity and specificity, provide a comprehensive assessment of thalassemia screening strategies, and indicate that NGS is a competitive screening method, especially among populations with a high prevalence of disease.Genet Med advance online publication 26 January 2017.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Biomarkers
  • China / epidemiology
  • China / ethnology
  • Codon
  • Ethnic Groups / genetics
  • Gene Frequency
  • Genetic Testing
  • Heterozygote*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Mass Screening
  • Middle Aged
  • Mutation
  • Phenotype
  • Premarital Examinations
  • Prevalence
  • Young Adult
  • alpha-Globins / genetics
  • alpha-Thalassemia / diagnosis*
  • alpha-Thalassemia / epidemiology
  • alpha-Thalassemia / genetics*
  • beta-Globins / genetics
  • beta-Thalassemia / diagnosis*
  • beta-Thalassemia / epidemiology
  • beta-Thalassemia / genetics*

Substances

  • Biomarkers
  • Codon
  • alpha-Globins
  • beta-Globins