Human subtelomeric duplicon structure and organization

Anthony Ambrosini,Sheila Paul,Harold Riethman,Sufen Hu

doi:10.1186/gb-2007-8-7-r151

Anthony Ambrosini, Sheila Paul + Show 2 more

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https://doi.org/10.1186/gb-2007-8-7-r151

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Journal: Genome Biology	Publication Date: Jan 1, 2007
Citations: 97	License type: cc-by

Affiliation: The Wistar Institute, Princeton University

Abstract

The sequence divergence within subtelomeric duplicon families varies considerably, as does the organization of duplicon blocks at subtelomere alleles; a class of duplicon blocks was identified that are subtelomere-specific.

Highlights

Human subtelomeric segmental duplications ('subtelomeric repeats') comprise about 25% of the most distal 500 kb and 80% of the most distal 100 kb in human DNA
In order to analyze their sequence organization in a systematic manner, we developed a set of rules to identify modules of DNA defined by sequence similarity between segments of subtelomeric DNA from single telomeres and the assembled human genome
Adjacent and properly oriented BLAST matches with ≥90% nucleotide sequence identity and ≥1 kb in size were assembled into chains; the query sequence and each aligned region identified in this manner were termed 'duplicons' defined by that query, and this set of homologous sequences is a single 'module'

Summary

Introduction

Human subtelomeric segmental duplications ('subtelomeric repeats') comprise about 25% of the most distal 500 kb and 80% of the most distal 100 kb in human DNA. Segmental duplications, defined operationally as duplicated stretches of genomic DNA at least 1 kb in length with >90% nucleotide sequence identity, comprise roughly 5% of euchromatin in the human genome [1] They are preferential sites of genomic instability, associated with recurrent pathologyassociated chromosome breakpoints [2], large-scale copy number polymorphisms [3,4], and evolutionary chromosome breakpoint regions [5]. The overall size, sequence content, and organization of subtelomeric segmental duplications relative to the terminal (TTAGGG)n repeat tracts and to subtelomeric single-copy DNA are different for each subtelomere [6], and the large-scale polymorphisms (50 kb to 500 kb) found near many human telomeres seem to be due primarily to variant combinations of subtelomeric segmental duplications [10,11,13]. The architecture of each human subtelomere region is determined largely by its specific subtelomeric segmental duplication content and organization, which vary from telomere to telomere and are often allele-specific

Results

Discussion

Conclusion