title: Molecular evidences of single mutational events followed by recurrent crossing-overs in the common delta-globin alleles in the Mediterranean area.
abstract: The human delta-globin gene (HBD) is one of the beta-like globin genes expressed in adults. In the Mediterranean countries the carriers of delta-thalassemia defects or Hb A2-variants are >1% and about 40/70 known alleles have been found in families with this ethnic origin. The scope of this study was to investigate the variability of the gene and of the chromosomal background in order to highlight the origin and spreading of the delta-globin gene alleles in the Mediterranean area. We carried out the characterization of the delta-globin gene alleles and of RFLP-haplotypes, SNPs and one microsatellite associated with them in 231 carriers originating principally from East Sicily. Seventeen alleles were identified, of which five were new. The chromosomes associated with mutated alleles from unrelated carriers were 158; the allele Hb A2-Yialousa accounted for about 75% of relative frequency, Hb A2-Mitsero for about 8%. The alleles were associated with RFLP 5'-haplotypes "- - - -" or "+ - + +", prevalent in the Mediterranean area, except Hb A2-Mitsero associated with the 5'-haplotype "Benin" "- - - +" and the Hb A2' associated with "+ - - +", both of African origin. Each allele showed linkage with one haplotype with these exceptions. The Hb A2-Yialousa showed heterogeneity of the 5'-haplotype in 2/58 chromosomes; the Hb A2-Mitsero showed SNPs and (A)gamma-microsatellite typical of a "Benin" haplotype found associated with the Hb C and Hb S chromosomes; the Hb A2-Yialousa (14/58 chromosomes), Hb A2-Mitsero, Hb A2-Pylos, Hb A2-Fitzroy showed heterogeneity in the 3'-haplotypes and beta-globin gene SNPs. The Hb A2-Coburg was found associated with the haplotype "+ - + +/+ +" different from that already reported "- - - -/+ -". With the exception of this last allele, the linkage of each mutation with a core of RFLPs or SNPs around or inside the delta-globin locus suggested the unicentric origin of the mutations followed by recurrent recombination events causing the chromosomal background heterogeneity.
authors.affiliation: Istituto di Genetica e Biofisica Adriano Buzzati Traverso, CNR, Naples, Italy. lacerra@igb.cnr.it
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lacerra
authors.forename: Gennaro
authors.initials: G
authors.lastname: Musollino
authors.forename: Clelia
authors.initials: C
authors.lastname: Scarano
authors.forename: Laura F
authors.initials: LF
authors.lastname: Lagona
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Caruso
authors.forename: Rosario
authors.initials: R
authors.lastname: Testa
authors.forename: Romeo
authors.initials: R
authors.lastname: Prezioso
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Noce
authors.forename: Emilia
authors.initials: E
authors.lastname: Medulla
authors.forename: Maria G
authors.initials: MG
authors.lastname: Friscia
authors.forename: Lucia
authors.initials: L
authors.lastname: Mastrullo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Caldora
authors.forename: Lucia
authors.initials: L
authors.lastname: Nota
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaudiano
authors.forename: Carmelo
authors.initials: C
authors.lastname: Magnano
authors.forename: Calogero
authors.initials: C
authors.lastname: Ciaccio
authors.forename: Maria A
authors.initials: MA
authors.lastname: Romeo
authors.forename: Clementina
authors.initials: C
authors.lastname: Carestia
mesh_terms: D000483:Alleles; D001483:Base Sequence; D003434:Crossing Over, Genetic; D017931:DNA Primers; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D019083:Mediterranean Region; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D017931:DNA Primers; D005914:Globins