There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Elaine Green |
| Institution: | Plymouth University |
| Department: | Plymouth University Peninsula Schools of Medicine |
| Country: | |
| Proposed Analysis: | I would like to request access to the whole genome sequence BAM file data for the 128 Alzheimer’s disease cases and 267 control individuals to characterise the germline retrortransposon L1 elements. This study will be based at Plymouth University, UK and is a funded PhD study (PUPSMED, Plymouth University Peninsula School of Medicine and Dentistry), under the supervision of Drs Elaine Green (PI) and Robert Belshaw. Dr Elaine Green has extensive experience in identifying genetic architecture that contributes to psychiatric and neurological disorders, studying both common and rare genetic variants, including single nucleotide polymorphisms and structural variants such as copy number variations, and more recently the potential contribution of retrotransposons. Robert Belshaw has experience of genome sequencing analyses to score the presence of specific integrations of another type of retroelement (human endogenous retroviruses). The current pipeline will be modified to mine L1elements. Computer facilities at Plymouth University are ideal for this project and include a High Performance computer facility and linux servers. This project will concentrate on the subclass of transposable elements that are still copying within the human genome, LINEs (long interspersed nuclear elements), specifically L1 elements. Retrotransposition of L1 elements can affect the human genome by generating new insertions and post-translational rearrangements creating deleterious sequence variants and aberrant expression. Genome-scale approaches have shown that retrotransposition occurs at a high frequency in somatic cells particularly the brain which is of interest in this study. It is thought that somatic L1 retrotransposition during neurogenesis is a potential route to creating genotypic variation in neurons with in turn will generate phenotypic diversity. As such it has been suggested that retrotransposons may play a role in for example, neurogenesis, aging, and neurodegenerative diseases. We aim to characterise the germline L1 present in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) case / control sample set. Initially, the genome location of all known full length potentially active L1 elements using on-line databases and published data will be catalogued. Using this information the germline L1s in both AD and controls individuals will be identified by analysing whole genome sequencing data and statistically compare L1 elements present in cases compared to controls, taking into account a) number b) location c) individual presence or combination of L1s. In addition, we plan to identify if single nucleotide polymorphisms (SNPs) are in high linkage disequilibrium (LD) with polymorphic L1s which would provide a SNP driven genome-wide association approach to studying L1s rather than costly and time consuming NGS approach. Finally, we plan to explore genomic position of genome-wide associated SNPs with AD and known L1s to determine if L1s are potentially the casual variant. |
| Additional Investigators |
