Department of Medical Genetics, University of British Columbia
Canada Excellence Research Chair in Neurogenetics and Translational Neurosciences
Don Rix British Columbia Leadership Chair in Genetic Medicine
Director, Centre for Applied Neurogenetics (CAN)
Djavad Mowafhagian Centre for Brain Health
Professor
phone: 6048227753
fax: 6048220361

RESEARCH INTERESTS

Genetic and functional analysis of neurologic and neurodegenerative disorders. Dr. Farrer’s focus is Parkinson’s disease and related movement disorders. Within multicase pedigrees statistical genetics/linkage analysis has been used to identify mutations in novel genes underlying monogenic disease, whereas genome-wide association and next-generation sequencing has identified pathogenic risk factors. Population genetics is currently active in more than 20 countries spanning five continents, including studies in Australia, Canada, England, Faroes, France, Korea, Norway, Taiwan and Tunisia. Functional neuroscience of the mutated genes, including a-synuclein, dynactin p150Glued, leucine-rich repeat kinase 2, elongation initiation factor 4G1, vacuolar protein sorting 35 and receptor mediated endocytosis-8 (DNAJC13) includes the generation and characterization of transgenic, cre-conditional knock-in and knock-out mouse models.

Core techniques include molecular genetics (next-generation and Sanger sequencing, Sequenom and Taqman genotyping), bioinformatics and statistical genetics (genome alignment and annotation, pedigree and population genetics with linkage and association methods), molecular and cell biology (construct design and cloning, primary neuronal culture, live-cell confocal imaging, biochemistry), electrophysiology, pharmacology and behaviour (including microdialysis voltammetry and optogenetics in brain slice). Molecular insights in disease pathogenesis now provide the rational and tools for novel therapeutic advances.

Funding comes from the Canadian Federal Government (CERC, CIHR, CFI), the Province of British Columbia, Borealis & Life Labs, with Genome BC, the National Institutes of Health, the Michael J Fox Foundation, the Parkinson`s Disease Foundation and partnerships with the Pharmaceutical industry. Investment from the latter is primarily directed towards translational research. See the Centre of Applied Neurogenetics homesite (www.can.ubc.ca) for more details.

SELECTED PUBLICATIONS

Trinh J, Guella I, Farrer MJ. Disease Penetrance of Late-Onset Parkinsonism: A Meta-analysis. JAMA Neurol. 2014 Oct 20. doi: 10.1001/jamaneurol.2014.1909. [Epub ahead of print] PubMed PMID: 25330418.

Beccano-Kelly DA, Volta M, Munsie LN, Paschall SA, Tatarnikov I, Co K, Chou P, Cao LP, Bergeron S, Mitchell E, Han H, Melrose HL, Tapia L, Raymond LA, Farrer MJ, Milnerwood AJ. LRRK2 overexpression alters glutamatergic presynaptic plasticity, striatal dopamine tone, postsynaptic signal transduction, motor activity and memory. Hum Mol Genet. 2014 Oct 24. pii: ddu543. [Epub ahead of print] PubMed PMID: 25343991.

Beccano-Kelly DA, Kuhlmann N, Tatarnikov I, Volta M, Munsie LN, Chou P, Cao LP, Han H, Tapia L, Farrer MJ, Milnerwood AJ. Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice. Front Cell Neurosci. 2014 Sep 26;8:301. doi:10.3389/fncel.2014.00301. eCollection 2014. PubMed PMID: 25309331; PubMed Central PMCID: PMC4176085.

Vilariño-Güell C, Rajput A, Milnerwood AJ, Shah B, Szu-Tu C, Trinh J, Yu I, Encarnacion M, Munsie LN, Tapia L, Gustavsson EK, Chou P, Tatarnikov I, Evans DM, Pishotta FT, Volta M, Beccano-Kelly D, Thompson C, Lin MK, Sherman HE, Han HJ, Guenther BL, Wasserman WW, Bernard V, Ross CJ, Appel-Cresswell S, Stoessl AJ, Robinson CA, Dickson DW, Ross OA, Wszolek ZK, Aasly JO, Wu RM, Hentati F, Gibson RA, McPherson PS, Girard M, Rajput M, Rajput AH, Farrer MJ. DNAJC13 mutations in Parkinson disease. Hum Mol Genet. 2014 Apr 1;23(7):1794-801. doi:10.1093/hmg/ddt570. Epub 2013 Nov 11. PubMed PMID: 24218364; PubMed CentralPMCID: PMC3999380.

Hinkle KM, Yue M, Behrouz B, Dächsel JC, Lincoln SJ, Bowles EE, Beevers JE, Dugger B, Winner B, Prots I, Kent CB, Nishioka K, Lin WL, Dickson DW, Janus CJ, Farrer MJ, Melrose HL. LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors. Mol Neurodegener. 2012 May 30;7:25. doi: 10.1186/1750-1326-7-25. PubMed PMID:22647713; PubMed Central PMCID: PMC3441373.

Wider C, Ross OA, Nishioka K, Heckman MG, Vilariño-Güell C, Jasinska-Myga B, Erketin-Taner N, Rademakers R, Graff-Radford NR, Mash DC, Papapetropoulos S,Duara R, Uchikado H, Wszolek ZK, Farrer MJ, Dickson DW. An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer’s and Lewy body pathology. J Neurol Neurosurg Psychiatry. 2012 Apr;83(4):424-9. doi: 10.1136/jnnp-2011-301413. Epub 2012 Jan 30. PubMed PMID: 22291217; PubMed Central PMCID: PMC3623699.

Chartier-Harlin MC, Dachsel JC, Vilariño-Güell C, Lincoln SJ, Leprêtre F, Hulihan MM, Kachergus J, Milnerwood AJ, Tapia L, Song MS, Le Rhun E, Mutez E, Larvor L, Duflot A, Vanbesien-Mailliot C, Kreisler A, Ross OA, Nishioka K, Soto-Ortolaza AI, Cobb SA, Melrose HL, Behrouz B, Keeling BH, Bacon JA, Hentati E, Williams L, Yanagiya A, Sonenberg N, Lockhart PJ, Zubair AC, Uitti RJ, Aasly JO, Krygowska-Wajs A, Opala G, Wszolek ZK, Frigerio R, Maraganore DM, Gosal D, Lynch T, Hutchinson M, Bentivoglio AR, Valente EM, Nichols WC, Pankratz N, Foroud T, Gibson RA, Hentati F, Dickson DW, Destée A, Farrer MJ. Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease. Am J Hum Genet. 2011 Sep 9;89(3):398-406. PubMed PMID: 21907011.

Ross OA, Soto-Ortolaza AI, Heckman MG, Aasly JO, Abahuni N, Annesi G, Bacon JA, Bardien S, Bozi M, Brice A, Brighina L, Van Broeckhoven C, Carr J, Chartier-Harlin MC, Dardiotis E, Dickson DW, Diehl NN, Elbaz A, Ferrarese C, Ferraris A, Fiske B, Gibson JM, Gibson R, Hadjigeorgiou GM, Hattori N, Ioannidis JP, Jasinska-Myga B, Jeon BS, Kim YJ, Klein C, Kruger R, Kyratzi E, Lesage S, Lin CH, Lynch T, Maraganore DM, Mellick GD, Mutez E, Nilsson C, Opala G, Park SS, Puschmann A, Quattrone A, Sharma M, Silburn PA, Sohn YH, Stefanis L, Tadic V, Theuns J, Tomiyama H, Uitti RJ, Valente EM, van de Loo S, Vassilatis DK, Vilariño-Güell C, White LR, Wirdefeldt K, Wszolek ZK, Wu RM, Farrer MJ; on behalf of the Genetic Epidemiology Of Parkinson’s Disease (GEO-PD) Consortium. Association of LRRK2 exonic variants with susceptibility to Parkinson’s disease: a case-control study. Lancet Neurol. 2011 Aug 30. [Epub ahead of print] PubMed PMID: 21885347.

Vilariño-Güell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, Soto-Ortolaza AI, Cobb SA, Wilhoite GJ, Bacon JA, Behrouz B, Melrose HL, Hentati E, Puschmann A, Evans DM, Conibear E, Wasserman WW, Aasly JO, Burkhard PR, Djaldetti R, Ghika J, Hentati F, Krygowska-Wajs A, Lynch T, Melamed E, Rajput A, Rajput AH, Solida A, Wu RM, Uitti RJ, Wszolek ZK, Vingerhoets F, Farrer MJ. VPS35 mutations in Parkinson disease. Am J Hum Genet. 2011 Jul 15;89(1):162-7. PubMed PMID: 21763482; PubMed Central PMCID: PMC3135796.

Höglinger GU, Melhem NM, Dickson DW, Sleiman PM, Wang LS, Klei L, Rademakers R, de Silva R, Litvan I, Riley DE, van Swieten JC, Heutink P, Wszolek ZK, Uitti RJ, Vandrovcova J, Hurtig HI, Gross RG, Maetzler W, Goldwurm S, Tolosa E, Borroni B, Pastor P; PSP Genetics Study Group, Cantwell LB, Han MR, Dillman A, van der Brug MP, Gibbs JR, Cookson MR, Hernandez DG, Singleton AB, Farrer MJ, Yu CE, Golbe LI, Revesz T, Hardy J, Lees AJ, Devlin B, Hakonarson H, Müller U, Schellenberg GD. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet. 2011 Jun 19;43(7):699-705. doi: 10.1038/ng.859. PubMed PMID: 21685912; PubMed Central PMCID: PMC3125476.

Winner B, Melrose HL, Zhao C, Hinkle KM, Yue M, Kent C, Braithwaite AT, Ogholikhan S, Aigner R, Winkler J, Farrer MJ, Gage FH. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. Neurobiol Dis. 2011 Mar;41(3):706-16. Epub 2010 Dec 16. PubMed PMID: 21168496; PubMed Central PMCID: PMC3059106.

Melrose HL, Daechsel JC, Behrouz B, Lincoln SJ, Yue M, Hinkle KM, Kent CB, Korvatska E, Taylor JP, Witten L, Liang YQ, Beevers JE, Boules M, Dugger BN, Serna VA, Gaukhman A, Yu X, Castanedes-Casey M, Braithwaite AT, Ogholikhan S, Yu N, Bass D, Tyndall G, Schellenberg GD, Dickson DW, Janus C, Farrer MJ. Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice. Neurobiol Dis. 2010 Jul 24. [Epub ahead of print]. PubMed PMID: 20659558.

Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, Hirsch EC, Farrer M, Schapira AH, Halliday G. Missing pieces in the Parkinson’s disease puzzle. Nat Med. 2010 Jun;16(6):653-61. Epub 2010 May 23. Review. PubMed PMID: 20495568.

Farrer MJ, Hulihan MM, Kachergus JM, Dächsel JC, Stoessl AJ, Grantier LL, Calne S, Calne DB, Lechevalier B, Chapon F, Tsuboi Y, Yamada T, Gutmann L, Elibol B, Bhatia KP, Wider C, Vilariño-Güell C, Ross OA, Brown LA, Castanedes-Casey M,Dickson DW, Wszolek ZK. DCTN1 mutations in Perry syndrome. Nat Genet. 2009 Feb;41(2):163-5. Epub 2009 Jan 11. PubMed PMID: 19136952; PubMed Central PMCID: PMC2813485.

Vilariño-Güell C, Soto AI, Lincoln SJ, Ben Yahmed S, Kefi M, Heckman MG, Hulihan MM, Chai H, Diehl NN, Amouri R, Rajput A, Mash DC, Dickson DW, Middleton LT, Gibson RA, Hentati F, Farrer MJ. ATP13A2 variability in Parkinson disease. Hum Mutat. 2009 Mar;30(3):406-10. PubMed PMID: 19085912; PubMed Central PMCID: PMC2650009.

Lewis J, Melrose H, Bumcrot D, Hope A, Zehr C, Lincoln S, Braithwaite A, He Z, Ogholikhan S, Hinkle K, Kent C, Toudjarska I, Charisse K, Braich R, Pandey RK, Heckman M, Maraganore DM, Crook J, Farrer MJ. In vivo silencing of alpha-synuclein using naked siRNA. Mol Neurodegener. 2008 Nov 1;3:19. PubMed PMID: 18976489; PubMed Central PMCID: PMC2612658.

Ishihara-Paul L, Hulihan MM, Kachergus J, Upmanyu R, Warren L, Amouri R, Elango R, Prinjha RK, Soto A, Kefi M, Zouari M, Sassi SB, Yahmed SB, El Euch-Fayeche G, Matthews PM, Middleton LT, Gibson RA, Hentati F, Farrer MJ. PINK1 mutations and parkinsonism. Neurology. 2008 Sep 16;71(12):896-902. Epub 2008 Aug 6. PubMed PMID: 18685134; PubMed Central PMCID: PMC2676945.

Ross OA, Braithwaite AT, Skipper LM, Kachergus J, Hulihan MM, Middleton FA, Nishioka K, Fuchs J, Gasser T, Maraganore DM, Adler CH, Larvor L, Chartier-Harlin MC, Nilsson C, Langston JW, Gwinn K, Hattori N, Farrer MJ. Genomic investigation of alpha-synuclein multiplication and parkinsonism. Ann Neurol. 2008 Jun;63(6):743-50. PubMed PMID: 18571778.

Hulihan MM, Ishihara-Paul L, Kachergus J, Warren L, Amouri R, Elango R, Prinjha RK, Upmanyu R, Kefi M, Zouari M, Sassi SB, Yahmed SB, El Euch-Fayeche G, Matthews PM, Middleton LT, Gibson RA, Hentati F, Farrer MJ. LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study. Lancet Neurol. 2008 Jul;7(7):591-4. Epub 2008 Jun 6. Erratum in: Lancet Neurol. 2008 Aug;7(8):675. PubMed PMID: 18539535.

Vilariño-Güell C, Farrer MJ, Lin SC. A genetic risk factor for periodic limb movements in sleep. N Engl J Med. 2008 Jan 24;358(4):425-7. PubMed PMID:18216367.

Fuchs J, Nilsson C, Kachergus J, Munz M, Larsson EM, Schüle B, Langston JW, Middleton FA, Ross OA, Hulihan M, Gasser T, Farrer MJ. Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology. 2007 Mar 20;68(12):916-22. Epub 2007 Jan 24. PubMed PMID: 17251522.

Farrer MJ. Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet. 2006 Apr;7(4):306-18. Review. PubMed PMID: 16543934.

Kachergus J, Mata IF, Hulihan M, Taylor JP, Lincoln S, Aasly J, Gibson JM, Ross OA, Lynch T, Wiley J, Payami H, Nutt J, Maraganore DM, Czyzewski K, Styczynska M, Wszolek ZK, Farrer MJ, Toft M. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet. 2005 Apr;76(4):672-80. Epub 2005 Feb 22. PubMed PMID: 15726496; PubMed Central PMCID: PMC1199304.

Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Müller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004 Nov 18;44(4):601-7. PubMed PMID: 15541309.

Skipper L, Wilkes K, Toft M, Baker M, Lincoln S, Hulihan M, Ross OA, Hutton M, Aasly J, Farrer M. Linkage disequilibrium and association of MAPT H1 in Parkinson disease. Am J Hum Genet. 2004 Oct;75(4):669-77. Epub 2004 Aug 3. PubMed PMID: 15297935; PubMed Central PMCID: PMC1182054.

Singleton AB*, Farrer M*, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson’s disease. Science. 2003 Oct 31;302(5646):841. PubMed PMID: 14593171. (*equal first)

Cookson MR, Lockhart PJ, McLendon C, O’Farrell C, Schlossmacher M, Farrer MJ. RING finger 1 mutations in Parkin produce altered localization of the protein. Hum Mol Genet. 2003 Nov 15;12(22):2957-65. Epub 2003 Sep 30. PubMed PMID: 14519684.

Farrer M, Chan P, Chen R, Tan L, Lincoln S, Hernandez D, Forno L, Gwinn-Hardy K, Petrucelli L, Hussey J, Singleton A, Tanner C, Hardy J, Langston JW. Lewy bodies and parkinsonism in families with parkin mutations. Ann Neurol. 2001 Sep;50(3):293-300. PubMed PMID: 11558785.