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PMID: 17284672 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

AT-rich repeats associated with chromosome 22q11.2 rearrangement disorders shape human genome architecture on Yq12.

Genome research ·Vol. 17 ·No. 4 ·2007-04-00 ·Pages 451-60

Babcock M, Yatsenko S, Stankiewicz P, Lupski JR, Morrow BE

Abstract

Low copy repeats (LCRs; segmental duplications) constitute approximately 5% of the sequenced human genome. Nonallelic homologous recombination events between LCRs during meiosis can lead to chromosomal rearrangements responsible for many genomic disorders. The 22q11.2 region is susceptible to recurrent and nonrecurrent deletions, duplications as well as translocations that are mediated by LCRs termed LCR22s. One particular DNA structural element, a palindromic AT-rich repeat (PATRR) present within LCR22-3a, is responsible for translocations. Similar AT-rich repeats are present within the two largest LCR22s, LCR22-2 and LCR22-4. We provide direct sequence evidence that the AT-rich repeats have altered LCR22 organization during primate evolution. The AT-rich repeats are surrounded by a subtype of human satellite I (HSAT I), and an AluSc element, forming a 2.4-kb tripartite structure. Besides 22q11.2, FISH and PCR mapping localized the tripartite repeat within heterochromatic, unsequenced regions of the genome, including the pericentromeric regions of the acrocentric chromosomes and the heterochromatic portion of Yq12 in humans. The repeat is also present on autosomes but not on chromosome Y in other hominoid species, suggesting that it has duplicated on Yq12 after speciation of humans from its common ancestor. This demonstrates that AT-rich repeats have shaped or altered the structure of the genome during evolution.

MeSH Terms
AT Rich Sequence Base Sequence Chromosome Aberrations Chromosome Disorders/genetics Chromosome Mapping Chromosomes, Human, Pair 22/genetics Chromosomes, Human, Y/genetics Gene Duplication Genome, Human Heterochromatin Humans In Situ Hybridization, Fluorescence Male Repetitive Sequences, Nucleic Acid
Chemicals
Heterochromatin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Babcock Melanie
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Yatsenko Svetlana
Stankiewicz Pawel
Lupski James R
Morrow Bernice E
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.5651507
Published
2007-04-00
Epub
2007-00-06
Pages
451-60
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC1832092
Subset
IM
Grants
NICHD NIH HHS · P01 HD039420 · United States
NICHD NIH HHS · P01 HD39420 · United States
External Links
PubMed source DOI: 10.1101/gr.5651507 PMC Full Text View journal details
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