The focus of research in the Raskind laboratory is to identify and study genes responsible for human inherited disorders, both simple and complex. We investigate a variety of neurogenetic disorders, including spastic paraparesis, myokymia, paroxysmal chorea, and ataxias. Probands are ascertained, families are recruited and linkage analyses are carried out. After mapping the location and narrowing the interval containing the gene, candidates are prioritized and evaluated to identify the gene responsible for the disease. Recently, we have discovered that mutations in a serine/threonine kinase gene, protein kinase C gamma, are responsible for an autosomal dominant spinocerebellar ataxia (SCA14). As part of a broad approach to understanding this disease, in-vitro functional assays and creation of mouse models are underway.
In addition to diseases that are inherited in a simple Mendelian fashion, behavioral disorders that have complex inheritance patterns are studied. In particular, as part of the UW Multidisciplinary Learning Disabilities Center, we are investigating the genetics of dyslexia and related learning disabilities. The targeted phenotypes are based on performance on tests that evaluate reading, writing and spelling ability, as well as those that assess executive function. Multigenerational families are being studied to characterize, model and map genetic subtypes of dyslexia.
Allikmets R, Raskind WH, Hutchinson A, Schueck ND, Dean M, Koeller DM: Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hum Molec Genet 8:743-749, 1999.
Raskind WH, Hsu L, Berninger VW, Thomson JB, Wijsman EM: Familial aggregation of phenotypic subtypes in dyslexia. Behavior Genetics 30:385-399, 2000.
Wijsman EM, Peterson D, Leutenegger A-L, Thomson JB, Goddard KAB, Hsu L, Berninger VW, Raskind WH: Segregation analyses of individual measures of dyslexia I: Nonword memory and Digit span. Am J Hum Genet 67: 631-646, 2000.
Yu C, Niakan KK, Matsushita M, Stamatoyannopoulos G, Orkin SH, and Raskind WH: X-linked thrombocytopenia with thalassemia due to a mutation in the amino-finger of GATA-1 affecting DNA-binding rather than FOG-1 interaction. Blood 100: 2040-2045, 2002.
Hsu L, Berninger VW, Thomson JB, Wijsman EM, Raskind WH. Familial aggregation of dyslexia phenotypes: paired correlated measures. Am J Med Genet (Neuropsych Genet). 114: 471-478, 2002
Brkanac Z, Fernandez M, Matsushita M, Lipe H, Wolff J, Bird TD, Raskind WH. Autosomal dominant sensory/motor neuropathy with ataxia (SMNA): linkage to chromosome 7q22-q32. Am J Med Genet (Neuropsych section). 114: 450-457, 2002
Brkanac Z, Bylenok L, Fernandez M, Matsushita M, Lipe H, Wolff, J, Nochlin D, Raskind WH, Bird TD: A new dominant spinocerebellar ataxia is linked to chromosome 19q13.4. Arch Neurol 59: 1291-1295, 2002.
Chen D-H, Brkanac Z, Verlinde CLMJ, Tan X-J, Bylenok L, Nochlin D, Matsushita M, Lipe H, Wolff J, Fernandez M, Cimino PJ, Bird TD, Raskind WH. Missense mutations in the regulatory domain of PKCg: a new mechanism for dominant nonepisodic cerebellar ataxia. Am J Hum Genet 72: 839-849, 2003.
Chapman NH, Igo RP, Thomson JB, Matsushita M, Brkanac Z, Holzman T, Berninger VW, Wijsman EM, Raskind WH. Linkage analyses of four regions previously implicated in dyslexia: confirmation of a locus on chromosome 15q. In press, Am J Med Genet (Neuropsych Genet).
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