Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Whole Exome Sequencing in Familial Parkinson Disease

ABSTRACT:

We have an ongoing study that has recruited families having at least a sibling pair with Parkinson disease (PD). Families have been screened for mutations in known PD causative genes (LRRK2, parkin, etc). Following review of families without a causative mutation, we selected families for whole exome sequencing that had the strongest history of PD and with the most definitive diagnosis. All families have at least 3 affected family members who were evaluated as part of this study. Only affected family members were included for whole exome sequencing.

PROVIDER: phs000376.v1.p1 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Publications

Genomewide association study for susceptibility genes contributing to familial Parkinson disease.

Pankratz Nathan N Wilk Jemma B JB Latourelle Jeanne C JC DeStefano Anita L AL Halter Cheryl C Pugh Elizabeth W EW Doheny Kimberly F KF Gusella James F JF Nichols William C WC Foroud Tatiana T Myers Richard H RH

Human genetics 20081106 6

Five genes have been identified that contribute to Mendelian forms of Parkinson disease (PD); however, mutations have been found in fewer than 5% of patients, suggesting that additional genes contribute to disease risk. Unlike previous studies that focused primarily on sporadic PD, we have performed the first genomewide association study (GWAS) in familial PD. Genotyping was performed with the Illumina HumanCNV370Duo array in 857 familial PD cases and 867 controls. A logistic model was employed ...[more]

PMID: 18985386

Publication: 1/5

Similar Datasets

Whole Exome Sequencing in Familial Parkinson Disease

Project description:We have an ongoing study that has recruited families having at least a sibling pair with Parkinson disease (PD). Families have been screened for mutations in known PD causative genes (LRRK2, parkin, etc). Following review of families without a causative mutation, we selected families for whole exome sequencing that had the strongest history of PD and with the most definitive diagnosis. All families have at least 3 affected family members who were evaluated as part of this study. Only affected family members were included for whole exome sequencing.

| phs000376 | dbGaP

Inefficient DNA repair is an aging-related modifier of Parkinson disease

Project description:The underlying relation between Parkinson disease (PD) etiopathology and its major risk factor, aging, is largely unknown. The nature of the specific age-related mechanisms promoting PD onset is experimentally difficult to elucidate because aging is a highly complex process contributed by multiple factors. Recent evidence, however, established a strong and causative link between genome stability and aging. To investigate a possible nexus between DNA damage accumulation, aging, and PD we examined DNA repair pathways associated with aging in laboratory animal models and human cases. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that NER-defective mice exhibit typical PD-like pathological alterations, including decreased dopaminergic innervation in the striatum, increased phospho-synuclein levels, and defects in mitochondrial respiration. NER mouse mutants are also more sensitive to the prototypical PD toxin MPTP and their transcriptomic landscape shares important similarities with that of PD patients. Overall, our results demonstrate that specific defects in DNA repair impact the dopaminergic system, are associated with human PD pathology, and might therefore constitute a novel risk factor for PD by affecting the aging process.

2016-11-13 | GSE75000 | GEO

Olfactory proteomics in Parkinson disease

Project description:Olfactory dysfunction is one of the earliest features in Lewy-type alpha-synucleinopathies (LTS) such as Parkinson´s disease (PD). However, the underlying molecular mechanisms associated to smell impairment is poorly understood. To reveal the missing links in the biochemical understanding of olfactory dysfunction in PD, we have applied mass spectrometry-based proteomics in postmortem olfactory bulbs (OBs) dissected from parkinsonian subjects with different LTS staging respect to elderly controls (n= 24, mean age 79 years).

2018-10-24 | PXD008036 | Pride

Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease

Project description:Neuroinflammation and accumulation of alphα-synuclein (α-syn) are core features of Parkinson disease (PD). We found that α-syn-induced neuroinflammation is driven by antigen presentation from CNS resident macrophages. A subset of these, border-associated macrophages (BAMs), expand and express genes and proteins necessary for immune cell recruitment, infiltration, and antigen presentation, whereas depletion of BAMs prevents neuroinflammation and neurodegeneration. These results point to a critical role for BAMs in initiating PD pathogenesis.

2021-06-20 | GSE178498 | GEO

New approaches in genetic analysis to predict for CRC risk.

Project description:Interventions: The aim of this research is to find the undiscovered gene or genes responsible for hereditary colorectal cancer, and to understand how the gene(s) cause colorectal cancer. One of the best approaches used to find the answers to these questions is to study families where there are several family members affected with colorectal cancer. Case probands and their relatives (affected and unaffected) will be recruited (20 ml) of blood will be obtained on one occasion from each participant Where tissues from affected family members have already been obtained (paraffin embedded tumour tissue in blocks) we will seek permission to access this material for DNA extraction. The duration of study will be approximately 48 months. Primary outcome(s): To identify molecular markers of potential value in understanding predisposition to CRC by their association with gene variants that increase the risk of CRC. The study will be a family based analysis of SNP genotypes for cases and controls within families and between families. Transmission of disease associated SNPs will be assessed to determine within-family association and linkage and then to calculate across-family associations.[2-3 blood samples per week over 36 months approx] Study Design: Purpose: Natural history;Duration: Cross-sectional;Selection: Defined population;Timing: Both

| 2452082 | ecrin-mdr-crc

Parkinson-associated SNCA enhancer variants revealed by open chromatin in mouse dopamine neurons

Project description:The progressive loss of midbrain (MB) dopaminergic (DA) neurons defines the motor features of Parkinson disease (PD) and modulation of risk by common variation in PD has been well established through GWAS. Anticipating that a fraction of PD-associated genetic variation mediates their effects within this neuronal population, we acquired open chromatin signatures of purified embryonic mouse MB DA neurons. Correlation with >2,300 putative enhancers assayed in mice reveals enrichment for MB cis-regulatory elements (CRE), data reinforced by transgenic analyses of six additional sequences in zebrafish and mice. One CRE, within intron 4 of the familial PD gene SNCA, directs reporter expression in catecholaminergic neurons of transgenic mice and zebrafish. Sequencing of this CRE in 986 PD patients and 992 controls reveals two common variants associated with elevated PD risk. To assess potential mechanisms of action, we identify proteins whose binding is impacted by these enhancer variants. Additional genotyping across the SNCA locus identifies a single PD-associated haplotype, containing the minor alleles of both of the aforementioned PD-risk variants. Our work posits a model for how common variation at SNCA may modulate PD risk and highlights the value of cell context-dependent guided searches for functional non-coding variation.

2018-11-14 | GSE122450 | GEO

Cystic leukoencephalopathy without megalencephaly

Project description:The cystic leukoencephalopathy without megalencephaly has been defined as distinct autosomal-recessive syndrome of quasi-static encephalopathy with normo- or microcephaly, impaired psychomotor development and characteristic pattern on brain MRI. We identified mutations in the gene encoding the RNASET2 glycoprotein in seven affected individuals as the cause of disease. The results suggest that RNASET2 plays an important role in central nervous system myelination and development. 2-Color dye swap design independent for two different families including technical and biologial replicates for affected family members (disease) and not affected family members (controls).

2009-06-02 | E-GEOD-11964 | biostudies-arrayexpress

Neuron-Derived Exosomes as a tool for the study of Parkinson disease: a rapid workflow for morphology, miRNA and proteomic characterization.Neuron-Derived Exosomes as a tool for the study of Parkinson disease: a rapid workflow for morphology, miRNA and proteomic characterization.Neuron-Derived Exosomes as a tool for the study of Parkinson disease: a rapid workflow for morphology, miRNA and proteomic characterization.

Project description:Neuron derived exosomes have been enriched from plasma using L1CAM antigen. Vesicles were enriched from plasma of Parkinson Disease patients and controls. The NDE morphology was observed by transmission electron microscope (TEM). miRNA-155 content was studied both in PD-NDE and control-NDE. LC-MS/MS was applied to verify the reproducibility of the NDE enrichment procedure and to assay PD-NDE protein profiles.

2021-09-09 | PXD020794 | Pride

CIDR: Genome Wide Association Study in Familial Parkinson Disease (PD)

Project description:This proposal brings together the two largest NIH funded genetic studies focused on the identification of novel genes that influence the risk of PD. These two studies, PROGENI (PI: Tatiana Foroud; R01NS037167) and GenePD (PI: Richard Myers; R01NS036711) have been evaluating and recruiting families with two or more PD affected members for more than 8 years and represent the largest such cohorts world-wide. The combined sample has more than 1,000 PD families. Each study has used rigorous clinical criteria to assess their study participants. Unlike previous genome wide association studies (GWAS) in PD, all the PD cases in this proposal have a positive family history of disease. In the vast majority of these families, the index PD case has at least one sibling with the disease. Thus, the sample is unique for having substantial evidence for a genetic contribution to disease. The control group for this study consists of samples previously collected and maintained by the NINDS Repository. Genome-wide, single nucleotide polymorphism (SNP) genotyping services were provided by <a href="http://www.cidr.jhmi.edu/">the Center for Inherited Disease Research (CIDR)</a>. Data analyses will focus on the identification of SNPs associated with PD susceptibility and the age of onset of disease.

| phs000126 | dbGaP

Proteomic analysis of secretory granules in dopaminergic neurons of Parkinson`s disease

Project description:Parkinson disease (PD) is the second most common age-related neurodegenerative disorder, which is related to neurotransmitter secretion impartment and the dysfunction of vesicle transport. Secretory granules (SGs) are a class of intracellular vesicles different from synaptic vesicles (SVs) in neurons and the neuroendocrine cells. They represent the primary subcellular site for the biosynthesis, storage and releasing of the neuropeptides, neurotransmitters and hormones. In the current study, we characterized the proteome of secretory granules in dopaminergic neurons in PD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify proteins in SGs. A total of 4249 proteins were identified in the SGs in normal and MPP+-treated SH-Sy5Y dopaminergic neurons in total. This study regarded the biological alternations of SGs in PD as an entry point. By studying the significantly differentially expressed proteins, it is helpful to better understand the molecular mechanisms of SGs disorders in the pathology of PD, and provide a basis for vesicle transport theory in pathogenesis of PD.

2021-08-26 | PXD023937 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data