Genetic variability at the PARK16 locus

Arianna Tucci, Mike A. Nalls, Henry Houlden, Tamas Revesz, Andrew B. Singleton, Nicholas W. Wood, John Hardy, Coro Paisán-Ruiz

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Parkinson's disease (PD) is a complex neurodegenerative disease which is clinically heterogeneous and pathologically consists of loss of dopaminergic neurons in the substantia nigra and intracytoplasmic neuronal inclusions containing alpha-synuclein aggregations known as Lewy bodies. Although the majority of PD is idiopathic, pathogenic mutations in several mendelian genes have been successfully identified through linkage analyses. To identify susceptibility loci for idiopathic PD, several genome-wide association studies (GWAS) within different populations have recently been conducted in both idiopathic and familial forms of PD. These analyses have confirmed SNCA and MAPT as loci harboring PD susceptibility. In addition, the GWAS identified several other genetic loci suggestively associated with the risk of PD; among these, only one was replicated by two different studies of European and Asian ancestries. Hence, we investigated this novel locus known as PARK16 for coding mutations in a large series of idiopathic pathologically proven PD cases, and also conducted an association study in a case-control cohort from the United Kingdom. An association between a novel RAB7L1 mutation, c.379-12insT, and disease (P-value=0.0325) was identified. Two novel coding variants present only in the PD cohort were also identified within the RAB7L1 (p.K157R) and SLC41A1 (p.A350V) genes. No copy number variation analyses have yet been performed within this recently identified locus. We concluded that, although both coding variants and risk alleles within the PARK16 locus seem to be rare, further molecular analyses within the PARK16 locus and within different populations are required in order to examine its biochemical role in the disease process.

Original languageEnglish
Pages (from-to)1356-1359
Number of pages4
JournalEuropean Journal of Human Genetics
Volume18
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • PARK16 locus
  • association studies
  • genetics

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