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Nucleic Acids Research, 1990, Vol. 18, No. 11 3353-3361
© 1990

GENOME STRUCTURE AND MAPPING

Characterization and organization of DNA sequences adjacent to the human telomere associated repeat (TTAGGG)n

Bernhard Weber*, Colin Collins, Carolyn Robbins, R. Ellen Magenis3, Allen D. Delaney1, Joe W. Gray2 and Michael R. Hayden

Department of Medical Genetics Vancouver V6T 2B5, Canada 1Biomedical Research Centre, University of British Columbia Vancouver V6T 2B5, Canada 2Lawrence Livermore National Laboratories, University of California Portland, OR, USA 3Department of Medical Genetics, Oregon Health Sciences University Portland, OR, USA

*To whom correspondence should be addressed at Department of Medical Genetics, University Hospital-UBC site, Room A68-2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Cananda

Received December 18, 1989. Accepted April 25, 1990.

We present a strategy for the cloning of DNA sequences adjacent to the tandemly repeated DNA sequence (TTAGGG)n. Sequence analysis of 14 independently isolated clones revealed the presence of non-repetitive sequences immediately adjacent to or flanked by blocks of the simple repeat (TTAGGG)n. In addition, we provide sequence information on two previously undescribed tandemly repeated sequences, including a 9 bp repeat and a modification of the (TTAGGG)n repeat. Using different mapping approaches six sub-clones, free of the TTAGGG repeat, were assigned to a single human chromosome. Moreover, in situ hybridization mapped one of these subclones, G2 - 1H, definitively to the telomeric band on chromosome 4q. However, Bal 31 insensitivity suggests a location in a more subterminal region. All the (TTAGGG)n-adjacent unique sequences tested are highly conserved among primates but are not present in other mammalian species. Identification and mapping of TTAGGG-adjacent sequences will provide a refined insight into the genomic organization of the (TTAGGG)nrepeat. The isolation of chromosome specific TTAGGG-adjacent sequences from subtelomeric regions of all human chromosomes will serve as important end points for the genetic maps and will be useful for the molecular characterization of chromosomal rearrangements involving telomeres.


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