β-Thalassemia Haplotypes in Romania in the Context of Genetic Mixing in the Mediterranean Area

Abstract

The purpose of this meta-study was to investigate β-thalassemia (β-thal) mutations and their chromosomal background in order to highlight the origin and spread of thalassemia alleles in the European and Mediterranean areas. Screening of more than 100 new Romanian β-thal alleles was also conducted. The results suggest an ancient introduction of mutations at codon 39 (C > T) (HBB: c.118C > T) and IVS-I-6 (T > C) (HBB: c.92 + 6T > C) in Romania. A comparative study was performed based on restriction fragment length polymorphism (RFLP) haplotypes associated with β-thal mutations in Romania and in Mediterranean countries. Each common β-thal allele from different populations exhibits a high degree of haplotype similarity, a sign of a clear unicentric origin for the IVS-I-110 (G > A) (HBB: c.93-21G > A), IVS-I-6, IVS-II-745 (C > G) (HBB: c.316-106C > G) and codon 39 mutations (the 17a [+ − − − − + +], 13c [ − + + − − − +], 17c [ + − − − − − +] and 14a [− + + − + + + ] ancestral RFLP background, respectively), followed by recurrent recombination events. This study also showed that geographic distances played a major role in shaping the spread of the predominant β-thal alleles, whereas no genetic boundaries were detected between broad groups of populations living in the Middle East, Europe and North Africa. The analyses revealed some discrepancies concerning Morocco and Serbia, which suggest some peculiar genetic flows. Marked variations in β^A were observed between Southeast Asia and the Mediterranean, whereas a relative genetic homogeneity was found around the Mediterranean Basin. This homogeneity is undoubtedly the result of the high level of specific historic human migrations that occurred in this area.

• β-Globin gene cluster
• meta-analysis
• restriction fragment length polymorphism (RFLP) haplotypes
• Romania
• standardized nomenclature of RFLP haplotypes
• thalassemia

Acknowledgments

We extend our deepest thanks to Dr. Stephane Buhler (Départment de Génétique et Evolution, Unité d’Anthropologie, Genéve, Suisse), whose help, advice and supervision were invaluable. This manuscript is dedicated to the memory of Professor Lucian Gavrila.

Declaration of interest

These studies by Dr. Cherry, Dr. Talmaci and Professor Dr. Gavrila were supported by the following research projects: FP6-ITHANET, EGIDE, CNCSIS 201/2007 and PN II 41-045/2007; Dr. Perrin was supported by research project EGIDE. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.