Minisatellite sequences close to the short arm telomere of the human sex chromosomes

• Main Author: Inglehearn, Christopher Francis
• Published: University of Edinburgh 1988
• Subjects: 591.35
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652814

Cosmid CY29 is derived from a DNA library prepared from the human-mouse hybrid cell line 3E7, which contains multiple Y chromosomes. Sub-clone 29C1, derived from CY29, has been found to define a hypervariable locus within 23kb of the human pseudoautosomal telomere. This has been assigned the locus name DXYS14. The clone has contributed to a genetic map of the human pseudoautosomal region, and has been used to study properties of the adjacent telomere. This thesis describes an analysis of sequences at this locus. Maps of the short arm subtelomeric regions of three human sex chromosomes are presented. In addition, by following inheritance of 290 homology through selected pedigrees it has been possible to obtain data on subtelomeric regions of seven other sex chromosomes. From this data it is shown that a region containing 29C1 homologous sequence and sequence proximal to it are duplicated on some telomeres. Thus any individual may have two, three or four copies of 29C1 homologous sequence in total, with one or two on each sex chromosome. In addition, restriction fragments containing 29C1 homology vary in size due to variation in copy number of a minisatellite type repeat. Sequence data from three such fragments shows blocks of imperfect 31bp GC rich repeat units in variable numbers in a head to tail array. The consensus sequence of these repeats show some similarity to other, reported minisatellite sequences. However when used as a probe, a DXYS14 consensus repeat oligomer detects other hypervariable loci only weakly, even at low stringency. It appears therefore that the DXYS14 repeat represents a separate family of minisatellites present in one or two blocks per haploid genome, and isolated within 23kb of the human XY telomere. In one pedigree studied, a novel 29C1 homologous restriction fragment is shown to have arisen during male meiosis, probably by change in size of the repeat block. Sequence and mapping data indicate that the 29C1 repeat block and sequence proximal to it shows characteristics normally associated with a low methylation island. This region does not appear to be transcribed however, and in the light of knowledge of DNA structure around locus DXYS14, a gene at this site seems unlikely. Sequences homologous to 29C1 are found in a range of vertebrates, with strong homology in some primates yet none in others. The implications of these observations are discussed.