Characterization of Physical Gap Sizes at Human Telomeres

Abstract

Genome-wide physical and genetic mapping efforts have not yet fully addressed the problem of closure at the telomeric ends of human chromosomes. Targeted efforts at cloning human and mouse telomeres have succeeded in identifying unique sequences at most telomeres, but gap sizes between these telomere clones and the distal markers on integrated genetic/physical maps remain largely unknown. As telomeric regions are known to be the most gene-rich regions of the human genome, filling these gaps should have a high priority in completion of the Human Genome Project. We reported previously a first generation set of unique sequence probes for human telomeric regions. Of 41 human telomere regions, 33 were represented by unique clones with a known distance (Յ300 kb) from the end of the chromosome; clones for the remaining eight telomeric regions had not yet been identified and were represented by the most distal markers on the integrated genetic/physical map. We have identified unique telomere clones for four of the remaining telomeres, 9p, 12p, 15q, and 16p. To determine the telomeric gap size for these chromosomes and five other human telomeres, interphase FISH analysis was performed to measure the distance between each telomere clone and the corresponding most distal marker. These studies provide distance estimates ranging from <100 kb to >1 Mb, thus defining the physical mapping task for filling telomeric gaps.

Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes

“…These paralogous segments are distributed primarily in subtelomeric and pericentromeric locations, consistent with the distribution of segmental duplications found in a recent whole genome survey (Bailey et al 2001) and earlier FISH analyses (Ijdo et al 1991;Trask et al 1993;Hoglund et al 1995;Martin-Gallardo et al 1995;Ning et al 1996;Lese et al 1999;Ciccodicola et al 2000;Park et al 2000;Bailey et al 2002;Martin et al 2002). Subtelomeric homology spans ∼258 kb.…”

“…Two head-to-head arrays of degenerate telomere repeats are found at this site; their head-to-head orientation indicates that chromosome 2 resulted from a telomereto-telomere fusion (Ijdo et al 1991). Furthermore, crosshybridization between 2qFus and various subtelomeric regions has been observed by fluorescence in situ hybridization (FISH) (Ijdo et al 1991;Trask et al 1993;Hoglund et al 1995;Martin-Gallardo et al 1995;Ning et al 1996;Lese et al 1999;Ciccodicola et al 2000;Park et al 2000;Bailey et al 2002;Martin et al 2002). Thus, the fusion must have occurred after subtelomeric sequences present at the ends of the ancestral fusion partners had already duplicated to/from at least one other chromosome end.…”

Cryptic telomere imbalance: A 15‐year update

“…Until recently, significant gaps existed in the physical map of the human genome, particularly in the regions near telomeres [Lese et al, 1999] and centromeres [Eichler et al, 2004]. The major breakthrough in our ability to study human telomere structure and to fill these gaps was the development of targeted methods to clone mammalian telomeres [Cross et al, 1989;Riethman et al, 1989;Brown et al, 1990a].…”

Toward closing rice telomere gaps: mapping and sequence characterization of rice subtelomere regions

“…Subtelomeric regions have also been shown to be gene-rich (Bishop et al 2000;Riethman et al 2001;Scherf et al 2001;Bringaud et al 2002;reviewed by Barry et al 2003). Intense efforts to close telomere gaps and integrate telomere repeat stretches (TTAGGG) n into the human genome sequence have been successful using genetic and physical mapping of the human telomere regions (Lese et al 1999; and large telomere-terminal fragments cloned in specialized yeast artificial chromosome (YAC) cloning vehicles called half-YACs. The result has been the integration of 32 of the 96 telomere regions into the human genome draft sequence (Riethman 1997;Riethman et al 2001;Xiang et al 2001).…”