Psychiatry and Behavioral Sciences|
|Phone Numbers||(443) 923-2686|
Fax: (443) 923-2675
|School of Medicine Address||422 JFK|
707 N. Broadway
Baltimore MD 21205
|Link to Lab Homepage|
Research Topic: Molecular basis of neurological disorders
The Pevsner lab studies the molecular basis of childhood brain disorders. We focus on chromosomal abnormalities (measured with single nucleotide polymorphism or SNP arrays) as well as genetic variants (measured using whole genome, whole exome, or targeted sequencing). The lab specializes in bioinformatics approaches: we use computational tools to make progress in understanding disease, and we write software programs to facilitate our research. Our goals are to identify genes and proteins implicated in childhood disease, and to develop rational therapeutic strategies for treatment.
We recently identified mutations in GNAQ (encoding a G protein alpha subunit) as the cause of both Sturge-Weber syndrome (a rare neurocutaneous disorder) and port-wine stains (a commonly occurring birthmark affecting 1:333 people). This discovery was accomplished through whole genome sequencing and targeted next-generation sequencing. The mutation is somatic, mosaic, and activating, and suggests a possible treatment based on modulating specific signaling pathways.
Disease we currently study include:
• autism spectrum disorder
• Sturge-Weber syndrome
• self-injury and intellectual disability
Baugher JD, Baugher BD, Shirley MD, Pevsner J
. Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method. BMC Genomics. 2013 May 31;14:367. doi: 10.1186/1471-2164-14-367.PubMed Reference
Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J.
Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013 May 23;368(21):1971-9. doi: 10.1056/NEJMoa1213507.PubMed Reference
Kondo MA, Tajinda K, Colantuoni C, Hiyama H, Seshadri S, Huang B, Pou S, Furukori K, Hookway C, Jaaro-Peled H, Kano SI, Matsuoka N, Harada K, Ni K, Pevsner J
, Sawa A. Unique pharmacological actions of atypical neuroleptic quetiapine: possible role in cell cycle/fate control. Transl Psychiatry. 2013 Apr 2;3:e243. doi: 10.1038/tp.2013.19.PubMed Reference
Stevens EL, Heckenberg G, Baugher JD, Roberson ED, Downey TJ, Pevsner J.
Consanguinity in Centre d'Étude du Polymorphisme Humain (CEPH) pedigrees. Eur J Hum Genet. 2012; 10.1038/ejhg.2011.266.PubMed Reference
Shirley MD, Baugher JD, Stevens EL, Tang Z, Gerry N, Beiswanger CM, Berlin DS, Pevsner J.
Chromosomal variation in lymphoblastoid cell lines. Human Mutation. 2012 10.1002/humu.22062.PubMed Reference
Stevens EL, Baugher JD, Shirley MD, Frelin LP, Pevsner J.
Unexpected relationships and inbreeding in HapMap phase III populations. PLoS One. 2012; 7(11):e49575.PubMed Reference
Halper-Stromberg E, Frelin L, Ruczinski R, Scharpf R, Jie C, Carvalho B, Hao H, Hetrick K, Jedlicka A, Dziedzic A, Doheny K, Scott AF, Baylin S, Pevsner J
, Spencer F, Irizarry RA. Performance assessment of copy number microarray platforms using a spike-in experiment. Bioinformatics. 2011; 27(8):1052-1060.PubMed Reference
Stevens E, Heckenberg G, Roberson EDO, Baugher JD, Downey TJ, Pevsner J.
Inference of relationships in population data using identity-by-descent and identity-by-state. PLoS Genetics. 2011; 7(9):e1002287.PubMed Reference
Roberson EDO, Wohler ES, Hoover-Fong JE, Lisi E, Stevens EL, Thomas GH, Leonard J, Hamosh A, Pevsner J.
Genomic analysis of partial 21q monosomies with variable phenotypes. Eur. J. Human Genetics. 2010; 19(2):235-238.PubMed Reference
Sobreira NL, Cirulli ET, Avramopoulos D, Wohler E, Oswald GL, Stevens EL, Ge D, Shianna KV, Smith JP, Maia JM, Gumbs CE, Pevsner J
, Thomas G, Valle D, Hoover-Fong JE, Goldstein DB. Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. PLoS Genet. 2010 Jun 17;6(6):e1000991. doi: 10.1371/journal.pgen.1000991.PubMed Reference
Roberson ED and Pevsner J.
Visualization of shared genomic regions and meiotic recombination in high-density SNP data. PLoS ONE. 2009; 4(8):e6711.PubMed Reference
Ting JC, Roberson ED, Currier DG, Pevsner J.
Locations and patterns of meiotic recombination in two-generation pedigrees. BMC Med. Genet. 2009; 10(1):93.PubMed Reference