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.