An unusual DNA sequence observed in the [gamma] globin gene loci of two members of a Chinese family

Abstract

There are two nonallelic human y globin genes located on the short arm of ~hromosome #11 in the order 5'-Gy-Ay-3'. Various modifications of the two y genes have been reported and include: deletion·s., triplications., quadruplications and recently a quintuplication. These are :.generally created by one or more unequal crossovers in the y globin ge~e- _regions on adjacent chromosomes. During the c~urse of looking for a y0 thala~semia,. which might be due to a_ crossover within the y genes., two cases were found in the family W. · Bgl II mapping studies showed a 5 kb deletion at the y gene loci in these individuals. The ·Bgl II fragment from th(= y gene loci of R .W. was cloned into the phage vector ·oRl. Phage mapping showed that two out o·f the three Pst I sites within the Bgl II fragment were missing which suggested that the crossover might· have occurred within the y gene., possibly within the yIVS II region. Sequence analysis of the cloned fragment revealed an unusual sequence which had no sequence homology with the r gene region except for a small 264 .bp region near the 3' end. The orientation of the 264 bp fragmen~ is inverted _relat~ve to homologous sequences in the Gr and A'Y IVS II. . The unus~al sequence was computer analyzed for homology with every DNA sequence file in the EMBL data base and GenBank and did not show ·any significant homologies to._ all the available DNA sequences except for the 264 ~p _yIVS II homology. Sine~ mor~ than 99% of the DNA sequences in. the whole of nature still remain unknown., ~he origin of this unusual sequence is a question which mu.st ~wait further investigation.