Aims
To generate whole genome variation data on as many HD participants as possible who take part in Registry or Enroll-HD.
Projects
We are generating variant data using arrays of known variants throughout the genome and by direct sequencing. Variant genetic data can differentially influence different phenotypes, e.g. motor, cognitive or behavioural. Hence, variant data will be interpreted in the context of such phenotypes.
We highlighted the DNA damage response as an important modifier of HD age at motor onset. This refocused our attention on the CAG repeat mutation rather than the Huntingtin protein.
Publications directly arising from this work
- Keum JW, Shin A, Gillis T, Mysore JS, Abu Elneel K, Lucente D, Hadzi T, Holmans P, Jones L, Orth M, Kwak S, MacDonald ME, Gusella JF, Lee JM. The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease. Am J Hum Genet. 2016 Feb 4;98(2):287-98. PMID: 26849111.
- Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium. Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease. Cell. 2015 Jul 30; 162(3):516-26. PMID: 26232222
- Correia K, Harold D, Kim KH, Holmans P, Jones L, Orth M, Myers RH, Kwak S, Wheeler VC, MacDonald ME, Gusella JF, Lee JM. The Genetic Modifiers of Motor OnsetAge (GeM MOA) Website: Genome-wide Association Analysis for Genetic Modifiers of Huntington’s Disease. J Huntingtons Dis. 2015 Sep 29;4(3):279-84. PMID: 26444025
Publications arising from additional work of the working group
- L Jones, H Houlden, SJ Tabrizi. DNA repair in the trinucleotide repeat disorders. (2017) The Lancet Neurology 16 (1), 88-96. PMID: 27979358
- Bettencourt, C, Hensman Moss, D, Flower, M, Wiethoff, S, Brice, A, Goizet, C, Stevanin,G, Koutsis, G, Karadima, G, Panas, M, Yescas-Gómez, P, García-Velázquez, LE, Alonso-Vilatela, ME, Lima, M, Raposo, M, Traynor,B, Sweeney, M, Wood, N, Giunti, P, The SPATAX network, Durr, A, Holmans, P, Houlden, H, Tabrizi, SJ, Jones, L. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases. Annals of Neurology, 79(6), pp. 983-990. (10.1002/ana.24656). PMID: 27044000
- Moss DJH, Pardiñas AF, Langbehn D, Lo K, Leavitt BR, Roos R, Durr A, Mead S; TRACK-HD investigators; REGISTRY investigators; Holmans P, Jones L, Tabrizi SJ. Identification of genetic variants associated with Huntington’s disease progression: a genome-wide association study. Lancet Neurol. 2017 Sep;16(9):701-711. doi: 10.1016/S1474-4422(17)30161-8. Epub 2017 Jun 20. Erratum in: Lancet Neurol. 2017 Sep;16(9):683. doi: 10.1016/S1474-4422(17)30220-X. PMID: 28642124.
Contact
Lead Facilitators:
, Cardiff University
MRC Centre for Neuropsychiatric Genetics and Genomics
Cardiff, UK
, University College London
London, UK
Associated EHDN Language Area Coordinator:
, EHDN Lanco,
Italy
