DNA polymorphisms in north Sardinian newborns and their linkage with abnormal γ globin gene arrangements and with β^o-thalassemia

Fetal hemoglobin analysis and globin gene mapping have identified one type of β^o-thalassemia and four different γ globin gene arrangements among newborn babies from the northern part of Sardinia. The β^o-thalassemia with a nonsense mutation at codon 39 was found on two chromosomes, each with a distinct pattern of polymorphic restriction sites; one had the ^Aγ^T (^Aγ75 Ile → Thr) mutation, while the second did not. Four closely related haplotypes were identified for chromosomes with the ^Aγ^T mutation. The γ-thalassemia heterozygosity with the -^GAγ- hybrid gene fell into two categories. One apparently originated through crossing-over between mismatched chromosomes characterized by the most common haplotype, while the other had polymorphisms resembling those of a less frequently occurring chromosome. Chromosomes with the -^Gγ-^AGγ-^Aγ- triplication had polymorphic sites to be expected for this condition, being complimentary to the -^GAγ- thalassemias. Of the two additional γ globin gene variations the -^Gγ-^Gγ- arrangement was associated with the chromosome with the most commonly occurring haplotype, while the chromosome with the -^Aγ-^Aγ- arrangement had a haplotype characteristic for that with the ^Aγ^T mutation, which identified an -^Aγ-^Aγ^T- arrangement. The incidental discovery of a silent β-chain mutant, Hb Hamilton, with the Val → Ile substitution at position β11, in five newborns was also reported.