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

He J1,2, Song W3, Yang J3,4, Lu S5, Yuan Y5, Guo J5, Zhang J2, Ye K5, Yang F5, Long F3, Peng Z5, Yu H4, Cheng L3,6, Zhu B1,2.

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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 2017Genetics in Medicine (2017); doi:10.1038/gim.2016.218.