Applications of next generation sequencing in the screening and diagnosis of thalassemia: A mini-review

Abstract

Thalassemias are a group of inherited blood disorders that affects 5-7% of the world population. Comprehensive screening strategies are essential for the management and prevention of this disorder. Today, many clinical and research laboratories have widely utilized next-generation sequencing (NGS) technologies to identify diseases, from germline and somatic disorders to infectious diseases. Yet, NGS application in thalassemia is limited and has just recently surfaced due to current demands in seeking alternative DNA screening tools that are more efficient, versatile, and cost-effective. This review aims to understand the several aspects of NGS technology, including its most current and expanding uses, advantages, and limitations, along with the issues and solutions related to its integration into routine screening and diagnosis of thalassemias. Hitherto, NGS has been a groundbreaking technology that offers tremendous improvements as a diagnostic tool for thalassemia in terms of its higher throughput, accuracy, and adaptability. The superiority of NGS in detecting rare variants, solving complex hematological problems, and providing non-invasive alternatives to neonatal diagnosis cannot be overlooked. However, several pitfalls still preclude its use as a stand-alone technique over conventional methods.

Keywords: NGS; WES; WGS; targeted sequencing; thalassemia programs; α-thalassemia; β-thalassemia.

FIGURE 1

The general workflow for the screening and diagnosis of α- and β-thalassemia using traditional and NGS-based methods. Figure adapted from Chen et al. (28) and Nigam et al. (55). FBC, full blood count; HPLC, high-performance liquid chromatography; ARMS, amplification refractory multiple sequencing; PCR, polymerase chain reaction; MLPA, multiplex ligation-dependent probe amplification.