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

Abstract

ObjectivesThalassemia is a highly prevalent monogenic inherited disease in southern China. It is important to collect epidemiological data comprehensively for proper prevention and treatment.MethodsIn 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.ResultsIn 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.ConclusionsOur 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.

Large-scale screening of thalassemia in Ji’an, P.R. China

“…Guangxi Zhuang Autonomous Region (24.51%) [18], two high-incidence areas of alpha/betathalassemia. The frequency spectrum of alpha-and beta-thalassemia mutations in this study is similar to that previously described in South China, e.g., Chenzhou [12]. For the composite genotypes, αα/-- SEA and IVS-II-654 (C>T) /β N were more than other genotypes.…”

“…The two sets of variants were merged, filtered and sorted using an in-house program named mergeVariant. Finally, the HbVar [12] and…”

“…In recent years, a large-scale investigation of thalassemia was carried out in different regions of China [4,8,12], but the epidemiologic characteristics of thalassemia among people from Jiangxi Province, as one of the high-prevalence areas, especially those from Ji'an City, are not fully understood [13]. Ji'an is located in the central part of Jiangxi Province, with a total area of 25,300 square kilometers and a population of 4,956,600.…”

Development of a genomic DNA reference material panel for thalassemia genetic testing

“…Five types of α‐thalassemia deletions and two types of rare β‐globin gene deletions were analyzed by Gap‐PCR (Table 1). The detailed protocol of characterizing thalassemia associated variations was described previously 21,22 …”

Update in Laboratory Diagnosis of Thalassemia

“…NGS has enabled researchers to diagnose and understand complex diseases through whole-genome sequencing, exome sequencing, or targeted gene panels (Yang et al, 2013;Stark et al, 2016). Recently, NGS has been applied for thalassemia screening (He et al, 2017;Shang et al, 2017;Zhang et al, 2019). Target NGS approach was designed to cover entire globin genes coding regions, their key regulatory regions, and modifier genes such as KLF1, BCL11A, HBS1L, and MYB.…”