α-Thalassehia Screeninc Reveals Quadruple ζ-Globin Genes in a Laotian Family

Abstract

In screening families for α-thalassemia (thal) by the Southern blot technique, several Laotian families were found which had anomalous ζ-globin haplotypes. The ζ-globin genes encode α-like embryonic hemoglobin subunits in the α-globin multigene complex on chromosome 16. There are normally two ζ-globin genes in this cluster: 5′ ζ2 and 3′ ψζ1. In our study, six individuals in three families had triple ζ-globin genes. Another family revealed a novel quadruple ζ-globin arrangement. Two abberrant fragments were seen in Eco R1, Bam H1, Bgl II and Hind III digests using a ζ-globin gene probe. These anomalous bands were in the 10 kb range consistent with duplication of the ζ-globin region. This haplotype interpretation was confirmed by Southern blot analyses using double digestions hybridized to a cDNA ζ-gene probe, and Pvu II digests probed with a 5′-ψζ1 intergenic fragment. Proposed mechanisms of recombination and implications of this novel arrangement are discussed.