s.mead@prion.ucl.ac.uk UCL Profile • PubMed |
Research Synopsis
The Institute of Prion Diseases Genetics, Epigenetics and bioinformatics group seeks to discover and understand genetic and epigenetic risk factors for Creutzfeldt-Jakob disease. Our core activity is genome wide (and epigenome wide) association study for which we receive samples from around the world. We have recently identified risk conferred by variants in or near to genes other than the prion protein gene. We are currently seeking to understand the mechanisms of these effects and their potential for therapeutic targeting. Other projects include the development of diagnostic classifiers using methylomics, use of population genetic techniques to explore the adaption of populations in Papua New Guinea to the kuru epidemic, the diagnosis of inherited prion disease, diagnosis of dementia and Huntington’s disease like syndromes using genomic technologies and development of biofluid biomarkers for CJD.
We are always interested to hear from potential new recruits to the team.
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| “Manhattan” Plot (as it appears like the Manhattan skyline) which shows the latest statistical findings from our genetic studies to find new risk genes in CJD. The different colours denote different human chromosomes. Each point shows the results of a statistical test comparing frequencies of the variation in patients compared to the healthy population. The dotted line shows the standard levels of statistical certainty required to claim a significant finding. |
Selected Publications
A Novel protective prion protein variant that colocalises with kuru exposure
Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T, Al-Dujaily H, Hummerich H, Beck J, Mein CA, Verzilli C, Whittaker J, Alpers MP, Collinge J. N Engl J Med. 2009 Nov 19;361(21):2056-65. doi: 10.1056/NEJMoa0809716. PubMed PMID: 19923577.
Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population
Beck J, Poulter M, Hensman D, Rohrer JD, Mahoney CJ, Adamson G, Campbell T, Uphill J, Borg A, Fratta P, Orrell RW, Malaspina A, Rowe J, Brown J, Hodges J, Sidle K, Polke JM, Houlden H, Schott JM, Fox NC, Rossor MN, Tabrizi SJ, Isaacs AM, Hardy J, Warren JD, Collinge J, Mead S Am J Hum Genet. 2013 Mar 7;92(3):345-53. doi: 10.1016/j.ajhg.2013.01.011. Epub 2013 Feb 21. PubMed PMID: 23434116; PubMed Central PMCID: PMC3591848.
Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia
Fratta P, Poulter M, Lashley T, Rohrer JD, Polke JM, Beck J, Ryan N, Hensman D, Mizielinska S, Waite AJ, Lai MC, Gendron TF, Petrucelli L, Fisher EM, Revesz T, Warren JD, Collinge J, Isaacs AM, Mead S.. Acta Neuropathol. 2013 Sep;126(3):401-9. doi: 10.1007/s00401-013-1147-0. Epub 2013 Jul 2. PubMed PMID: 23818065; PubMed Central PMCID: PMC3753468.
A novel prion disease associated with diarrhea and autonomic neuropathy
Mead S, Gandhi S, Beck J, Caine D, Gallujipali D, Carswell C, Hyare H, Joiner S, Ayling H, Lashley T, Linehan JM, Al-Doujaily H, Sharps B, Revesz T, Sandberg MK, Reilly MM, Koltzenburg M, Forbes A, Rudge P, Brandner S, Warren JD, Wadsworth JDF, Wood NW, Holton JL, Collinge J. N Engl J Med. 2013 Nov 14;369(20):1904-14. doi: 10.1056/NEJMoa1214747. Erratum in: N Engl J Med. 2014 Jan 9;370(2):188. Gallujipali, Dillip [corrected to Gajulapalli, Dilip]. PubMed PMID: 24224623; PubMed Central PMCID: PMC3863770.
Genetic risk factors for the posterior cortical atrophy variant of Alzheimer’s disease.
Schott JM, Crutch SJ, Carrasquillo MM, Uphill J, Shakespeare TJ, Ryan NS, Yong KX, Lehmann M, Ertekin-Taner N, Graff-Radford NR, Boeve BF, Murray ME, Khan QU, Petersen RC, Dickson DW, Knopman DS, Rabinovici GD, Miller BL, González AS, Gil-Néciga E, Snowden JS, Harris J, Pickering-Brown SM, Louwersheimer E, van der Flier WM, Scheltens P, Pijnenburg YA, Galasko D, Sarazin M, Dubois B, Magnin E, Galimberti D, Scarpini E, Cappa SF, Hodges JR, Halliday GM, Bartley L, Carrillo MC, Bras JT, Hardy J, Rossor MN, Collinge J, Fox NC, Mead S.. 2016 Aug;12(8):862-71. doi: 10.1016/j.jalz.2016.01.010. Epub 2016 Mar 15. PubMed PMID: 26993346; PubMed Central PMCID: PMC4982482.
Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral serie
Koriath C, Kenny J, Adamson G, Druyeh R, Taylor W, Beck J, Quinn L, Mok TH, Dimitriadis A, Norsworthy P, Bass N, Carter J, Walker Z, Kipps C, Coulthard E, Polke JM, Bernal-Quiros M, Denning N, Thomas R, Raybould R, Williams J, Mummery CJ, Wild EJ, Houlden H, Tabrizi SJ, Rossor MN, Hummerich H, Warren JD, Rowe JB, Rohrer JD, Schott JM, Fox NC, Collinge J, Mead S. Mol Psychiatry. 2018 Oct 2. doi: 10.1038/s41380-018-0224-0. [Epub ahead of print] PubMed PMID: 30279455; PubMed Central PMCID: PMC6330090.
Genome-wide association study in multiple prion diseases suggests genetic risk factors additional to PRNP
Mead S, Uphill J, Beck J, Poulter M, Campbell T, Lowe J, Adamson G, Hummerich H, Klopp N, Rückert IM, Wichmann HE, Azazi D, Plagnol V, Pako WH, Whitfield J, Alpers MP, Whittaker J, Balding DJ, Zerr I, Kretzschmar H, Collinge J. Hum Mol Genet. 2012 Apr 15;21(8):1897-906. doi: 10.1093/hmg/ddr607. Epub 2011 Dec 30. PubMed PMID: 22210626; PubMed Central PMCID: PMC3313791.