Molecular analysis of a novel subtelomeric repeat with polymorphic chromosomal distribution

117

119

Physical mapping data were combined with public draft and finished sequences to derive subtelomeric sequence assemblies for each of the 41 genetically distinct human telomere regions. Sequence gaps that remain on the reference telomeres are generally small,well-defined,and for the most part,restricted to regions directly adjacent to the terminal (TTAGGG)n tract. Of the 20.66 Mb of subtelomeric DNA analyzed, 3.01 Mb are subtelomeric repeat sequences (Srpt),and an additional 2.11 Mb are segmental duplications. The subtelomeric sequence assemblies are enriched >25-fold in short,internal (TTAGGG)n-like sequences relative to the rest of the genome; a total of 114 (TTAGGG)n-like islands were found,55 within Srpt regions,35 within one-copy regions,11 at one-copy/Srpt or Srpt/segmental duplication boundaries,and 13 at the telomeric ends of assemblies. Transcripts were annotated in each assembly,noting their mapping coordinates relative to their respective telomere and whether they originate in duplicated DNA or single-copy DNA. A total of 697 transcripts were found in 15.53 Mb of one-copy DNA,76 transcripts in 2.11 Mb of segmentally duplicated DNA,and 168 transcripts in 3.01 Mb of Srpt sequence. This overall transcript density is similar (within ∼10%) to that found genome-wide. Zinc finger-containing genes and olfactory receptor genes are duplicated within and between multiple telomere regions

Section: Sequence Organization Of Subtelomeric Dnasupporting

confidence: 89%

Mapping and Initial Analysis of Human Subtelomeric Sequence Assemblies

Riethman¹,

Ambrosini²,

Castañeda³

et al. 2004

117

119

“…Nonetheless, the existence of other families of large subtelomeric duplications, affecting an overlapping or a completely different set of chromosomes, is indicated by the genome distribution of other, completely unrelated, subtelomeric sequences (Cross et al 1990;Ijdo et al 1992;Martin-Gallardo et al 1995;Ciccodicola et al 2000). This possibility is supported by a recent report showing that large blocks of sequences may be found polymorphically duplicated at the short arm of all human acrocentric chromosomes (Piccini et al 2001).…”

Section: Discussionmentioning

confidence: 87%

Segmental Polymorphisms in the Proterminal Regions of a Subset of Human Chromosomes

Der-Sarkissian¹,

Vergnaud²,

Borde³

et al. 2002

The subtelomeric domains of chromosomes are probably the most rapidly evolving structures of the human genome. The highly variable distribution of large duplicated subtelomeric segments has indicated that frequent exchanges between nonhomologous chromosomes may have been taking place during recent genome evolution. We have studied the extent and variability of such duplications using in situ hybridization techniques and a set of well-defined subtelomeric cosmid probes that identify discrete regions within the subtelomeric domain. In addition to reciprocal translocation and illegitimate recombination events that could explain the observed mosaic pattern of subtelomeric regions, it is likely that homology-based recombination mechanisms have also contributed to the spread of distal subtelomeric sequences among particular groups of nonhomologous chromosome arms. The frequency and distribution of large-scale subtelomeric polymorphisms may have direct implications for the design of chromosome-specific probes that are aimed at the identification of cryptic subtelomeric deletions. Furthermore, our results indicate that the relevance of some of the telomere closures proposed within the present Human Genome Sequence draft are restricted to specific allelic variants of unknown frequencies

“…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.…”

Section: Division Of Human Biology Fred Hutchinson Cancer Research Cmentioning

confidence: 99%

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

Fan

Linardopoulou²,

Friedman³

et al. 2002

110

100

Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ∼100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans.