William Johnson
Professor

Human genetics. nervous system traits & diseases. linkage mapping. genomic markers. microsatellite polymorphisms. positional cloning

Laboratory of Molecular Neurogenetics

The major focus of our laboratory is to locate and clone genes for nervous system traits and diseases. To locate genes. we carry out parametric linkage mapping using the lod score method as well as non-parametric mapping using affected sib-pair methods. allelic association methods. and haplotype relative risk methods. After ascertaining the appropriate family material. collecting blood for DNA extraction or lymphoblast transformation. and determining the statistical power of the family collection. we test the pedigrees against a genomic map of polymorphic markers. Alleles of short tandem repeat (microsatellite) markers are determined for each individual and the pedigrees are analyzed using computer programs for parametric or non-parametric analysis. Genes are located more precisely by fine structure mapping and identified by the techniques of positional cloning.

The laboratory is currently working with a variety of neurological diseases and traits occurring in children and adults as well as those related to genes active during intrauterine development. These include two disorders on the X-chromosome: Pelizaeus-Merzbacher leukodystrophy and X-linked mental retardation. We are studying the role of folate-related genes in spina bifida cystica. a severe and common disorder of nervous system development in the fetus. and in other adverse outcomes of pregnancy. We are studying families with epilepsy. including febrile seizures to identify epilepsy genes. We are studying kindreds with degenerative diseases of the cerebellum (dominant and recessive cerebellar ataxias) and the basal ganglia (Parkinson's disease) to identify genes for these disorders. We are also studying the genetics of schizophrenia. certain cognitive disorders. and specific cognitive abilities.

Selected Publications

Buyske S. Williams TA. Mars AE. Stenroos ES. Ming SX. Wang R. Sreenath M. Factura MF. Reddy C. Lambert GH. Johnson WG. (2006) Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism. BMC Genet. 7(1):8

Desautels A. Turecki G. Montplaisir J. Xiong L. Walters AS. Ehrenberg BL. Brisebois K. Desautels AK. Gingras Y. Johnson WG. Lugaresi E. Coccagna G. Picchietti DL. Lazzarini A. Rouleau GA. (2005) Restless legs syndrome: confirmation of linkage to chromosome 12q. genetic heterogeneity. and evidence of complexity. Arch Neurol. 62(4):591-6.

Johnson WG. Scholl TO. Spychala JR. Buyske S. Stenroos ES. Chen X. (2005) Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery. Am J Clin Nutr. 81(3):664-8.

Ming X. Stein TP. Brimacombe M. Johnson WG. Lambert GH. Wagner GC. (2005) Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins. Leukotrienes and Essential Fatty Acids. 73(5):379-384.

Johnson WG. Stenroos ES . Spychala J. Buyske S. Chatkupt S. Ming X. (2004) A New 19 bp Deletion Polymorphism in Intron-1 of Dihydrofolate Reductase (DHFR) -- A risk factor for spina bifida acting in mothers during pregnancy? Am.J.Med.Genet. 124A(4): 339-45.

Doss-Pepe EW. Stenroos ES. Johnson WG. Madura K.(2003) Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis. Molecular & Cellular Biology. 23(18):6469-83.

Johnson WG. (2003) Teratogenic alleles and neurodevelopmental disorders. Bioessays 5(5):464-77.

Lazzarini. A.. Schwarz. K.O.. Jiang. S.. Stenroos. E.S.. Lehner. T.. and Johnson. W.G. (1997). X-Linked Pelizaeus-Merzbacher-like disease: exclusion of proteolipid protein (PLP) locus and documentation of a new locus on Xq. Neurology 49:824-832.

Polymeropoulos. M.H.. Lavedan. C.. Leroy. E.. Ide. S.E.. Dehejia. A.. Dutra. A.. Pike. B.. Root. H.. Rubenstein. J.. Boyer. R.. Stenroos. E.S.. Chandrasekharappa. S.C.. Athanassiadou. A.. Papapetropoulos. T.. Johnson. W.G.. Lazzarini. A.M.. Duvoisin. R.C.. Di Iorio. G.. Golbe. L.I.. and Nussbaum. R.L. (1997). Mutation in the alpha synuclein gene identified in families with Parkinson's disease. Science 276:2045-2047.

Johnson. W.G.. Kugler. S.L.. Stenroos. E.S.. Meulener. M.C.. Rangwalla. I.. Johnson. T.J.. Mandelbaum. D.E. (1996). Pedigree Analysis in Families with Febrile Seizures. Am J Med Genet 61:345-352.

Polymeropoulos. M.H.. Higgins. J.J.. Golbe. L.I.. Johnson. W.G.. Ide. S.E.. Di Iorio. G.. Sanges. G.. Stenroos. E.S.. Pho. L.T.. Schaffer. A.A.. Lazzarini. A.M.. Nussbaum. R.L.. and Duvoisin. R.C. (1996). Mapping of a gene for Parkinson's disease to chromosome 4q21-q23. Science 274:1197-1199.