Linked Life Data

19414482

Source:http://linkedlifedata.com/resource/pubmed/id/19414482

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2009-6-24
pubmed:abstractText
Ataxia telangiectasia (AT) is a chromosome instability (CIN) neurological syndrome arising from DNA damage response defects due to ATM gene mutations. The hallmark of AT is progressive cerebellar degeneration. However, the intrinsic cause of the neurodegeneration remains poorly understood. To highlight the relationship between CIN and neurodegeneration in AT, we monitored aneuploidy and interphase chromosome breaks (chromosomal biomarkers of genomic instability) in the normal and diseased brain. We observed a 2-3-fold increase of stochastic aneuploidy affecting different chromosomes in the cerebellum and the cerebrum of the AT brain. The global aneuploidization of the brain is, therefore, a new genetic phenomenon featuring AT. Degenerating cerebellum in AT was remarkably featured by a dramatic 5-20-fold increase of non-random DNA double-strand breaks and aneuploidy affecting chromosomes 14 and, to a lesser extend, chromosomes 7 and X. Novel recurrent chromosome hot spots associated with cerebellar degeneration were mapped within 14q12. In silico analysis has revealed that this genomic region contains two candidate genes (FOXG1B and NOVA1). The existence of non-random breaks disrupting specific chromosomal loci in neural cells with DNA repair deficiency supports the hypothesis that neuronal genome may undergo programmed somatic rearrangements. Investigating chromosome integrity in neural cells, we provide the first evidence that increased CIN can result into neurodegeneration, whereas it is generally assumed to be associated with cancer. Our data suggest that mosaic instability of somatic genome in cells of the central nervous system is more significant genetic factor predisposing to the brain pathology than previously recognized.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2656-69
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Increased chromosome instability dramatically disrupts neural genome integrity and mediates cerebellar degeneration in the ataxia-telangiectasia brain.
pubmed:affiliation
National Research Center of Mental Health, Russian Academy of Medical Sciences, Zagorodnoe sh. 2, Moscow 119152, Russia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't