Further delineation of nonhomologous-based recombination and evidence for subtelomeric segmental duplications in 1p36 rearrangements

The mechanisms involved in the formation of subtelomeric rearrangements are now beginning to be elucidated. Breakpoint sequencing analysis of 1p36 rearrangements has made important contributions to this line of inquiry. Despite the unique architecture of segmental duplications inherent to human subt...

Full description

Saved in:
Bibliographic Details
Published in:Human genetics 2009-06, Vol.125 (5-6), p.551-563
Main Authors: D'Angelo, Carla S, Gajecka, Marzena, Kim, Chong A, Gentles, Andrew J, Glotzbach, Caron D, Shaffer, Lisa G, Koiffmann, Célia P
Format: Article
Language:English
Subjects:
Analysis
Base Sequence
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cell Line
Chromosome Breakage
Chromosome Walking
Chromosomes
Chromosomes, Human, Pair 1 - genetics
Classical genetics, quantitative genetics, hybrids
Cloning, Molecular
Comparative Genomic Hybridization
DNA Repair
DNA sequencing
Fundamental and applied biological sciences. Psychology
Gene Duplication
Gene Function
Gene Rearrangement
Genetics of eukaryotes. Biological and molecular evolution
Genic rearrangement. Recombination. Transposable element
Human
Human Genetics
Humans
In Situ Hybridization, Fluorescence
Investigations
Laboratories
Metabolic Diseases
Methods, theories and miscellaneous
Molecular and cellular biology
Molecular genetics
Molecular Medicine
Molecular Sequence Data
Nucleotide sequencing
Oligonucleotide Array Sequence Analysis
Original Investigation
Recombination, Genetic
Sequence Analysis, DNA
Translocation, Genetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The mechanisms involved in the formation of subtelomeric rearrangements are now beginning to be elucidated. Breakpoint sequencing analysis of 1p36 rearrangements has made important contributions to this line of inquiry. Despite the unique architecture of segmental duplications inherent to human subtelomeres, no common mechanism has been identified thus far and different nonexclusive recombination-repair mechanisms seem to predominate. In order to gain further insights into the mechanisms of chromosome breakage, repair, and stabilization mediating subtelomeric rearrangements in humans, we investigated the constitutional rearrangements of 1p36. Cloning of the breakpoint junctions in a complex rearrangement and three non-reciprocal translocations revealed similarities at the junctions, such as microhomology of up to three nucleotides, along with no significant sequence identity in close proximity to the breakpoint regions. All the breakpoints appeared to be unique and their occurrence was limited to non-repetitive, unique DNA sequences. Several recombination- or cleavage-associated motifs that may promote non-homologous recombination were observed in close proximity to the junctions. We conclude that NHEJ is likely the mechanism of DNA repair that generates these rearrangements. Additionally, two apparently pure terminal deletions were also investigated, and the refinement of the breakpoint regions identified two distinct genomic intervals ~25-kb apart, each containing a series of 1p36 specific segmental duplications with 90-98% identity. Segmental duplications can serve as substrates for ectopic homologous recombination or stimulate genomic rearrangements.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-009-0650-9