Dr Alistair Pagnamenta
Research
The recent developments in next generation sequencing technology opens up a number of research opportunities that were not previously feasible. In a clinical genetics setting these methods are also becoming increasingly important as they will enable disease genes to be analysed in greater numbers. This is particularly important for genetically heterogeneous disorders where currently it was only possible to sequence the most common candidate genes using Sanger technology. My work within the Oxford BRC has involved 454 sequencing of patients' DNA and exome analysis of family trios with rare brain malformations.
I have also been part of the WGS500 project as part of the sequencing & experimental follow up team
Specific interests include autism and epilepsy genetics, mitochondrial disorders, copy number variation, and the ethical issues that are raised by recent relation developments in genomic technologies.
I also help out occasionally with Science in the Kitchen, related public engagement initiatives. Centre postcards: Autism SNPs, HeLa mitochondria.
Recent Biography
2010-present: Post-Doc research scientist using next generation sequencing in the BRC genomics group at The Wellcome Trust Centre for Human Genetics.
2007-2010: Post-Doc research scientist in the Monaco Group at The Wellcome Trust Centre for Human Genetics, researching the genetic of autism susceptibility.
2006-2007: Post-Doc at the Royal Free Medical School (University College London), studying the assembly pathway of human cytochrome-c oxidase using RNA interference. Funded by the United Mitochondrial Disease Foundation and supervised by Dr Jan-Willem Taanman, Clinical Neurosciences.
2002-2006: PhD at the Institute of Child Health (University College London): "Identification of Nuclear Genes Responsible for Mitochondrial Respiratory Chain Disorders in Childhood”. Funded by a CHRAT studentship and supervised by Dr Shamima Rahman, Biochemistry, Endocrinology & Metabolism Unit.
Talks, Prizes, etc
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Prize for joint 2nd highest cited paper published in EJHG in 2009 (A 15q13.3 microdeletion segregating with autism)
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Invited speaker at Autism Today (Edinburgh): 7th national conference. October 2010
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ASHG 2009 Trainee Research Semi-finalist award.
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Invited speaker at 5th International Meeting on Cryptic Chromosomal Rearrangements in Mental Retardation and Autism. April 2009.
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Review on Autism Genetics, SLI Consortium meeting, September 2008
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3rd Prize in the "Science at The Free" poster competition, July 2007: Cytochrome-c oxidase subassemblies in HeLa cells revealed by transcriptional silencing of nuclear-encoded subunits. Pagnamenta A.T. and Taanman J.W.
Recent Publications
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Pagnamenta A.T., Murray J.E., Yoon G., Akha E.S., Harrison V., Bicknell L.S., Ajilogba K., Stewart H., Kini U., Taylor J.C., Keays D.A., Jackson A.P. and Knight S.J. A novel nonsense CDK5RAP2 mutation in a Somali child with primary microcephaly and sensorineural hearing loss. Am J Med Genet part A 158A(10):2577-2582 (2012). PMID: 22887808
- Anney R., Klei L., Pinto D. et al. Individual common variants exert weak effects on the risk for autism spectrum disorders.Hum Mol Genet. Epub ahead of print August 2012. PMID: 22843504
- Holt R., Sykes N.H., Conceição I.C., Cazier J-B., Anney R.J.L., Oliveira G., Gallagher L., Vicente A., Monaco A.P. and Pagnamenta A.T. CNVs leading to fusion transcripts in individuals with autism spectrum disorder. EJHG 20:1141-7(2012). PMID: 22549408
- Pagnamenta A.T., Lise S., Harrison V., Stewart H., Jayawant S., Quaghebeur G., Deng A.T., Murphy V.E., Sadighi Akha E., Rimmer A., Mathieson I., Knight S.J.L., Kini U., Taylor J.C. and Keays D.A. Exome sequencing can detect pathogenic mosaic mutations present at low allele frequencies. JHG, 57:70-72 (2012). PMID: 22129557
- Pagnamenta A.T., Holt R., Yusuf M., Pinto D., Wing K., Betancur C., Scherer S.W., Volpi E.V., Monaco A.P. A family with autism and rare copy number variants disrupting the Duchenne/Becker muscular dystrophy gene DMD and TRPM3. Journal of Neurodevelopmental Disorders, 3(2):124-31 (2011). PMID:21484199
- Pagnamenta A.T., Khan H., Walker S., Gerrelli D., Wing K., Bonaglia M.C., Giorda R., Berney T., Mani E., Molteni M., Pinto D., Le Couteur A., Hallmayer J., Sutcliffe J.S., Szatmari P., Paterson A.D., Scherer S.W., Vieland V.J., Monaco A.P. Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability. Journal of Medical Genetics, 48:48-54. Editor's Choice. (2010) PMID: 20972252
- Fassone E., Duncan A., Taanman J.-W., Pagnamenta A.T., Sadowski M., Holand T., Qasim W., Rutland P., Calvo S., Mootha V., Bitner-Glindzicz M., Rahman S. FOXRED1, encoding a FAD-dependent oxidoreductase complex-I specific molecular chaperone, is mutated in infantile-onset mitochondrial encephalopathy. Human Molecular Genetics, Advanced online. (2010) PMID: 20858599.
- Anney R., Klei L., Pinto D., Regan R., Conroy J., Magalhaes T.R., Correia C., Abrahams B.S., Sykes N., Pagnamenta A.T. et al. A genomewide scan for common alleles affecting risk for autism. Hum Mol Genet, Advance Access 27 July (2010). PMID: 20663923.
- Pinto D., Pagnamenta A.T., Klei L., Anney R., et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466, 368-372 (2010). PMID: 20531469
- Pagnamenta A.T., Bacchelli E., de Jonge M.V., Mirza G., Scerri T., Minopoli F., Chiocchetti A., Ludwig K.U., Hoffmann P., Paracchini S., Lowy E., Harold D.H., Chapman J.A., Klauck S.M., Poustka F., Houben R.H., Staal W.G., Ophoff R.A., O’Donovan M.C., Williams J., Nöthen M.M., Schulte-Körne G., Deloukas P., Ragoussis J., Bailey A.J., Maestrini E., Monaco A.P., IMGSAC. Characterisation of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia. Biological Psychiatry 68, 320-328 (2010). PMID: 20346443
- Sousa I., Clark T.G., Holt R., Pagnamenta A.T., Mulder E.J., Minderaa R.B., Bailey A.J., Battaglia A., Klauck S.M., Poustka F., Monaco A.P., IMGSAC. Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry. Molecular Autism 1(7), (2010).
- Pagnamenta A.T. and Monaco A.P. Chromosomal Copy Number Variation in Psychiatric Disorders. European Psychiatric Review 1(2), 8-12 (2009).
- Weiss L.A., Arking D.E.; Gene Discovery Project of Johns Hopkins & the Autism Consortium, Daly M.J., Chakravarti A.. A genome-wide linkage and association scan reveals novel loci for autism. Nature 461(7265). 802-808 (2009). One of 195 collaborators involved with replication. PMID: 19812673.
- Maestrini E.*, Pagnamenta A.T.*, Lamb J.A.*, Bacchelli E., Sykes N.H., Sousa I., Toma C., Barnby G., Butler H., Winchester L., Scerri T.S., Minopoli F., Reichert J., Cai G., Buxbaum J.D., Korvatska O., Schellenberg G.D., Dawson G., de Bildt A., Minderaa R.B., Mulder E.J., Morris A.P., Bailey A.J., Monaco A.P., IMGSAC. * The first three authors contributed equally to this work. High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicates the IMMP2L-DOCK4 gene region in autism susceptibility. Molecular Psychiatry. Epub ahead of print (2009). PMID: 19401682.
- Sykes N.H., Toma C., Wilson N., Volpi E.V., Sousa I., Pagnamenta A.T., Tancredi R., Battaglia A., Maestrini E., Bailey A.J., Monaco A.P., IMGSAC. Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection. European Journal of Human Genetics 17(10), 1347-1353 (2009). PMID: 19384346.
- Pagnamenta A.T., Wing K., Akha E.S., Knight S.J., Bölte S., Schmötzer G., Duketis E., Poustka F., Klauck S.M., Poustka A., Ragoussis J., Bailey A.J., Monaco A.P., IMGSAC. A 15q13.3 microdeletion segregating with autism. European Journal of Human Genetics 17(5), 687-692 (2009). PMID: 19050728.
- Taanman J.W., Rahman S., Pagnamenta A.T., Morris A.A.M., Bitner-Glindzicz, M., Wolf N.I., Leonard J.V., Clayton P.T., Schapira A.H.V. Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion. Human Mutation 30(2), 248-254 (2009). PMID: 18828154.
Contact Details
Genomics - Taylor Group
Wellcome Trust Centre for Human Genetics
Roosevelt Drive
Headington
Oxford, OX3 7BN
UK
Tel: +44(0)1865 287660
Email: alistair@well.ox.ac.uk
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