instmctions): Core C will provide biobanking, genetic analysis and informatics services for all Cores and for Projects 1 and 2. Core C will maintain and distribute samples, cell lines and gene constructs. Core C will also assess the genetic contribution to familial and atypical parkinsonism, focusing on linked pathogenic mutations and associated susceptibility variants. There are four specific aims:
Aim 1) Informatics: To provide, maintain and improve data storage and integration among Cores B, C and D, and for Projects 1, 2 and 3. Minimal clinical, pathological and genealogical data includes major diagnoses, pedigree relationships and sample availability. Genotype data will be appended to sample identifiers. Core C will provide assistance with variant selection, descriptive statistics and power analyses to help manage sample and pedigree ascertainment.
Aim 2) Biobanking: Individual samples include blood, cell lines and brain tissue that are bar-coded and informatically tracked. DNA will be isolated from blood or frozen brain, and biospecimens will be quality controlled and archived. The repository includes cell lines and plasmids of cloned genes, linked or associated with parkinsonism, that serve as positive controls that may be distributed on request.
Aim 3) Assessment of rare and common variants in genes linked to parkinsonism: Complete gene sequencing will be performed based on disease inheritance pattern in multi-incident Parkinsonian families for SNCA, LRRK2, EIF4G1. VPS35, PRKN, PINK1 and DJ-1. All point mutations and quantitative exonic deletion/duplication mutations linked to monogenic forms of parkinsonism will also be examined. In addition, assessment of common established genetic risk factors will be included within our screens.
Aim 4) Provide core genotyping facilities to the projects of the Mayo Udall center and external Udall network: Genotyping of specific genes and variants will be required for Project 1 and Project 2. Core C will provide additional animal model genotyping as needed for Project 3. Core C will also support and foster established and new collaborations between Udall Centers and provide genetic analysis as requested.
Genetic discoveries in parkinsonism have revolutionized the research field directing in vitro and in vivo disease model systems and generating novel avenues of therapeutic development. To this aim Core C will provide biobanking, genotyping and infonnatics services for all Cores and Projects as required and additionally foster collaborations with the genetic component of other Udall Centers.
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