Abnormal gamma-globin gene arrangements in Sardinians

An extended survey of 8,103 Sardinian newborns has been conducted for the study of abnormal gamma-globin gene arrangements. Fetal hemoglobin analysis and globin gene mapping have identified five different arrangements in 24 babies: five (21%) were carriers of the -GA gamma- hybrid (thalassemic) gene, directing the synthesis of the A gamma chain and resulting in low (41%) G gamma chain and decreased Hb F levels; two (8%) carried the -A gamma-A gamma T- duplication, characterized by even lower (37%) G gamma levels; five (21%) carried the -G gamma-AG gamma-A gamma- triplication; one (4%) carried the -G gamma-G gamma-A gamma- triplication, and 11 (46%) the -G gamma-G gamma- duplication, all resulting in high G gamma levels (85, 83, and 88%, respectively). Thirty-six additional babies could be phenotypically classified as carriers of the same mutations. Haplotyping and gamma-chain composition showed that the crossover event generating the -GA gamma- hybrid gene and the corresponding -G gamma-AG gamma-A gamma- triplication has occurred on at least three different chromosomes. The -G gamma-G gamma- duplication was associated with the chromosome having haplotype I, and the -A gamma-A gamma T- with the chromosome of haplotype II. As many as 2,260 babies (28%) were heterozygous, and 254 (3%) homozygous for the A gamma T mutation. The incidence and relative distribution of these anomalies in Sardinia are different when compared with those of other ethnic groups.