Open AccessComprehensive analysis of mitochondrial and nuclear DNA variations in patients affected by hemoglobinopathies: A pilot study
Author(s) -
Ylenia Barbanera,
Francesco Arcioni,
Hovirag Lancioni,
Roberta La Starza,
Irene Cardinali,
Caterina Matteucci,
Valeria Nofrini,
Antonella Roetto,
Antonio Piga,
Paola Grammatico,
Maurizio Caniglia,
Cristina Mecucci,
Paolo Gorello
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0240632
Subject(s) - mitochondrial dna , mitochondrial disease , nuclear gene , genetics , thalassemia , biology , nuclear dna , hemoglobinopathy , genetic heterogeneity , haplotype , gene , phenotype , genotype , computational biology , bioinformatics , disease , medicine
The hemoglobin disorders are the most common single gene disorders in the world. Previous studies have suggested that they are deeply geographically structured and a variety of genetic determinants influences different clinical phenotypes between patients inheriting identical β-globin gene mutations. In order to get new insights into the heterogeneity of hemoglobin disorders, we investigated the molecular variations on nuclear genes (i.e. HBB , HBG2 , BCL11A , HBS1L and MYB) and mitochondrial DNA control region. This pilot study was carried out on 53 patients belonging to different continents and molecularly classified in 4 subgroup: β-thalassemia ( β + /β + , β 0 /β 0 and β + /β 0 )(15), sickle cell disease (HbS/HbS )(20), sickle cell/β-thalassemia ( HbS/β + or HBS/β 0 )(10), and non-thalassemic compound heterozygous ( HbS/HbC , HbO-Arab/HbC )(8). This comprehensive phylogenetic analysis provided a clear separation between African and European patients either in nuclear or mitochondrial variations. Notably, informing on the phylogeographic structure of affected individuals, this accurate genetic stratification, could help to optimize the diagnostic algorithm for patients with uncertain or unknown origin.