Genomic instability in the PARK2 locus is associated with Parkinson’s disease
PBN-AR
Instytucja
Instytut Matki i Dziecka
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Journal of Applied Genetics
ISSN
1234-1983
EISSN
2190-3883
Wydawca
SPRINGER HEIDELBERG
DOI
URL
Rok publikacji
2015
Numer zeszytu
4
Strony od-do
451-461
Numer tomu
56
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Autorzy
Pozostali autorzy
+ 5
Słowa kluczowe
en
Common fragile sites
FRA6E
Genomic rearrangements
Parkinson’s disease
PARK2
Open access
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Inne
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Creative Commons — Uznanie autorstwa
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Streszczenia
Język
en
Treść
Parkinson’s disease (PD) is a common neurodegenerative disorder affecting mostly elderly people, although there is a group of patients developing so-called early-onset PD (EOPD). Mutations in the PARK2 gene are a common cause of autosomal recessive EOPD. PARK2 belongs to the family of extremely large human genes which are often localised in genomic common fragile sites (CFSs) and exhibit gross instability. PARK2 is located in the centre of FRA6E, the third most mutation-susceptible CFS of the human genome. The gene encompasses a region of 1.3 Mbp and, among its mutations, large rearrangements of single or multiple exons account for around 50 %. We performed an analysis of the PARK2 gene in a group of 344 PD patients with EOPD and classical form of the disease. Copy number changes were first identified using multiplex ligation probe amplification (MLPA), with their ranges characterised by array comparative genomic hybridisation (aCGH). Exact breakpoints were mapped using direct sequencing. Rearrangements were found in eight subjects, including five deletions and three duplications. Rearrangements were mostly non-recurrent and no repetitive sequences or extended homologies were identified in the regions flanking breakpoint junctions. However, in most cases, 1–3 bp microhomologies were present, strongly suggesting that microhomology-mediated mechanisms, specifically non-homologous end joining (NHEJ) and fork stalling and template switching (FoSTeS)/microhomology-mediated break-induced replication (MMBIR), are predominantly involved in the rearrangement processes in this genomic region.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
587923
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