Impact of annotation error in α-globin genes on molecular diagnosis.

J Francis Borgio

PloS one 2017

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Recent studies on the variants in duplicated human alpha globin genes (HBA2 and HBA1) actively target the α-globin gene as molecular modulators for the treatment of β-thalassemia major. Identification of the exact position of variant in HBA1, HBA2 or its patchworks is mandatory to support the therapeutic aims in β-thalassemia major, by identifying specific modulators for the reactivation of fetal hemoglobin production. Hence, accurate identification of the variants in α-globin genes is crucial for the proper diagnosis, treatment and genetic counseling. The objective was to reveal the annotation errors produced in α-globin gene sequence analysis while using different analytic tools. An HBA2 gene sequence with the HBA2:c.95+2_95+6delTGAGG variant and a recently reported HBA12 gene convert have been taken as examples to prove annotation error in α-globin gene from different analytic tools. Although various bioinformatics tools used to predict variants are usually of high reliability, the current study using the an alpha globin 2 sequence with the HBA2:c.95+2_95+6delTGAGG variant and a recently reported HBA12 gene convert, has showcased ambiguous outputs among the three bioinformatics tools used and against the manual analytical method adopted. This report emphasizes the necessity for caution in the usage of DNA sequence analysis tools during molecular diagnosis and the importance of the selection of more appropriate tools for analysis. Furthermore, ethnic specific sequences should be considered as reference sequence for the analysis to bypass sequence dissimilarities among diverse populations.