Neurogenetics Research Program

http://snp.bumc.bu.edu

Richard H. Myers, PhD, Director, Professor of Neurology
Jemma B. Wilk, DSc, Assistant Professor, Department of Neurology
Anita L. DeStefano, PhD, Associate Professor, School of Public Health
Jeanne Latourelle, MS, Project Manager, GenePD Study, HD MAPS study, doctoral student, Epidemiology, BU SPH
Sally Williamson, BS, Senior Lab Technician
Mike Nagle, BS, Lab Technician
Tiffany Massood, BS, Study Coordinator, GenePD Study, HD MAPS Study
Jason Laramie, MS, Doctoral Student, Bioinformatics Program
Jen Tobin, BA, Doctoral Student, Department of Anatomy and Neurobiology  

The Neurogenetics Research Program is directed by Richard H. Myers, PhD, Professor of Neurology. Dr. Myers also has appointments at Boston University as a Professor in the Bioinformatics Program, College of Engineering; Professor in the Departments of Environmental Health, Epidemiology, and Biostatistics, School of Public Health; and Professor in the Sections of Preventive Medicine and Genetics, Department of Medicine.  He is a Consultant in Genetics in the Department of Neurology at the Massachusetts General Hospital.

The Neurogenetics laboratory is involved in a wide array of research projects which combine four main areas of expertise: (1) clinical expertise in understanding the phenotypic intricacies of the disease or trait under investigation, (2) wet lab analysis of genetic polymorphisms, gene expression profiling and gene sequencing to identify genes and genetic sequences associated with diseases and traits, (3) statistical genetic and genetic epidemiological methods to creatively analyze the association of phenotypic with genotypic information, and (4) bioinformatic assessment of gene structure and function to gain insight into the genetic mechanisms and pathways implicated.  The ability to apply this variety of expertise to the genetic analysis of traits and diseases of interest represents a major interest of the Neurogenetics Research Program.

The Neurogenetics Research Program is currently supported by several NIH funded projects and two Foundations.

1.        Huntington’s disease.   The lab has been part of the New England Huntington’s disease “Center without walls” (http://hdroster.iu.edu/AboutTheRoster/hdMaps.asp) program project grant since 1980, and has been NIH/NINDS funded through PO1 NS16367-26.  We coordinate the HD MAPS study, which is performing a genome wide association study to identify genes that modify onset age and other critical features of HD.

The Neurogenetics Laboratory receives substantial support from the Jerry McDonald Huntington’s disease research fund.

2.        Parkinson’s disease.   The lab directs the “GenePD Study” (http://www.bu.edu/genepd/index.htm), which is a consortium of twenty clinical programs specializing in Parkinson’s disease treatment around the world . This study has been funded since 1997 by the NIH/NINDS R01 NS36711-09.  The study has recruited more than 350 families and with two or more members (living or deceased) who meet diagnostic criteria for PD and DNA samples from more than 800 cases of familial PD. The goal of the study is to identify genes that influence risk for PD. We are currently performing a genome wide association study to identify genes that influence risk for PD.

The Neurogenetics Laboratory receives substantial support from the Bumpus Foundation Parkinson’s disease research fund.

3.        The HyperGEN study.  This is a multicenter study of genetic and non-genetic determinants of hypertension, funded since 1995 by the NIH/NHLBI U01 HL054471-12.  The Neurogenetics lab has focused on the adrenergic receptors genes and catecholamines and their relation to blood pressure and heart rate.

Several projects in the lab are derived from the NHLBI “Family Heart Study” (http://dsgweb.wustl.edu/fhscc/). The Family Heart Study is a multi-center population-based study of genetic and non-genetic determinants of coronary heart disease (CHD), artherosclerosis, and cardiovascular risk factors. A total of 5,348 members of 1,253 families completed an extensive clinic examination and another 627 individuals provided medical histories and blood samples at remote sites.

4.        Genetic Studies of Body Mass Indexon chromosome 7q32. This project is funded by the NIH/NHLBI HL68891-05 and follows up on a genome scan for Body Mass Index which produced a LOD score in excess of 5 on chromosome 7.  The major goals of this project are to identify genes related to obesity and body mass index in this region. 

5.        Mapping Adiposity QTLs in the NHLBI Family Heart Study on chromosome 13q14.  This project is funded by the NIH/NIDDK R0-1 DK068336-03 and builds upon a genome scan for Body Mass Index, performed in the Family Heart Study.  The study seeks to identify genes related to obesity by disequilibrium mapping under the linkage peak by focusing on families with the highest LOD scores in that region.

6.        Identifying Susceptibility Genes for Metabolic Syndrome on chromosome 2.  This application builds upon a genome scan for Metabolic Syndrome performed in the NHLBI Family Heart Study.  The work will be extended by disequilibrium mapping at chromosome 2q35-2q37, focusing on 1122 Caucasian subjects from FHS families with the highest LOD scores in that region. 

7.        FHS-SCAN Genome Wide Association Scan for Atherosclerosis Pathway Genes. This study aims to identify genes influencing coronary artery calcification (CAC) and other endophenotypes for the atherosclerosis pathway through a genome wide association scan (GWAS) performed in 1,000 participants in the NHLBI Family Heart Study-SubClinical Atherosclerosis Network (FHS-SCAN).

 

Recent Publications from the Neurogenetics Laboratory:

 

1.                   Wilk JB,Myers RH, Pankow JS, Hunt SC, Leppert MF, Freedman BI, Province MA, Ellison RC.  Adrenergic receptor polymorphisms associated with resting heart rate: The HyperGEN Study.  Annals Human Genetics 2006; 70:566-573.

2.                   An P, Freedman BI, Rich SS, Mandel SA, Arnett DK, Myers RH, Chen Y-D I, Hunt SC, Rao DC. Quantitative Trait Loci on Chromosome 8q24 for Pancreatic Β-Cell Function and 7q11 for Insulin Sensitivity in Obese Nondiabetic White and Black Families: Evidence from Genome-Wide Linkage Scans in the NHLBI Hypertension Genetic Epidemiology Network (HyperGEN) Study. Diabetes 2006; 55:551-558.

3.                   Sun M, Latourelle JC, Wooten GF, Lew MF, Klein C, Shill HA, Golbe LI, Mark MH, Racette BA, Perlmutter JS, Parsian A, Guttman M, Nicholson G, Xu G, Wilk JB, Saint-Hilaire MH, DeStefano AL, Prakash R, Williamson S, Suchowersky O, Labelle N, Growdon JH, Singer C, Watts RL, Goldwurm S, Pezzoli G, Baker KB, Pramstaller PP, Burn DJ, Chinnery PF, Sherman S, Vieregge P, Litvan I, Gillis T, MacDonald ME, Myers RH, Gusella JF.   Heterozygosity for Parkin Mutation Influences Onset Age in Familial Parkinson’s Disease: The GenePD Study. Archives of Neurology 2006;63:826-832. 

4.                   Laramie JM, Wilk JB,Hunt SC, Ellison RC, Chakravarti A, Boerwinkle E, Myers RH.  Evidence for a Gene Influencing Heart Rate on Chromosome 5p13-14 in a Meta-Analysis of Genome-Wide Scans from the NHLBI Family Blood Pressure Program.  BMC Medical Genetics 2006; 7:17.

5.                   Myers RH. Considerations for Genomewide Association Studies in Parkinson Disease. (editorial). American Journal of Human Genetics 2006; 78:1081.

6.                   Lloret A, Dragileva E, Teed A, Espinola J, Fossale E, Gillis T, Lopez E, Myers RH, MacDonald ME, Wheeler VC. Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington’s disease knock-in mice. Human Molecular Genetics 2006; 15:2015-2024.

7.                   Kishikawa S, Li J-L, Gillis T, Hakky MH, Warby S, Hayden M, MacDonald ME, Myers RH, Gusella JF.  Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington’s disease. Neurobiology of Disease 2006; 24:280-285.

8.                   Li J-L, Hayden MR, Warby SC, Durr A, Morrison PJ, Nance M, Ross CA, Margolis RL, Rosenblatt A, Squitieri F, Frati L, Gomez-Tortosa E, Ayuso Garcia C, Suchowersky O, Klimek ML, Trent RA, McCusker E, Novelletto A, Frontali M, Paulsen JS, Jones R, Ashizawa T, Lazzarini A, Wheeler VC, Prakash R, Xu G, Djoussé L, Mysore JS, Gillis T, Hakky M, Cupples LA, Saint-Hilaire MH, Cha J-HJ, Hersch SM, Penney JB, Harrison MB, Perlman SL, Zanko A, Abramson RK, Lechich AJ, Duckett A, Marder K, Conneally PM, Gusella JF, MacDonald ME, Myers RH. Genome-wide Significance for a Modifier of Age at Neurological Onset in Huntington Disease at 6q23-24: the HD MAPS Study. BMC Medical Genetics 2006, 7:71

9.                   Zeng W, Gillis T, Hakky M, Djoussé L, Myers RH, MacDonald ME, Gusella JF.  Genetic analysis of the GRIK2 modifier effect in Huntington’s disease. BMC Neuroscience 2006, 7:62.

10.                Wilk JB, Tobin JE, Suchowersky O, Shill H, Klein C, Wooten GF, Lew M, Mark MH, Guttman M, Watts RL, Singer C, Growdon J, Latourelle JC, Saint-Hilaire M, DeStefano AL, Prakash R, Williamson S, Berg CJ, Sun M, Goldwurm S, Pezzoli G, Racette BA, Perlmutter JS, Parsian A, Baker K, Giroux ML, Litvan I, Pramstaller PP, Nicholson GA, Burn DJ, Chinnery PF, Vieregge P, Slevin JT, Cambi F, MacDonald ME, Gusella JF, Myers RH, Golbe LI.  Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age: The GenePD Study.  Neurology 2006; 67:2206-2210.

11.                Kraja AT, Borecki IB, North K, Tang W, Myers RH, Hopkins PN, Arnett D, Corbett J, Adelman A, Province MA. Longitudinal and Age Trends of Metabolic Syndrome and its Risk Factors. The Family Heart Study. Nutrition & Metabolism 2006; 3:41-49.

12.                Feitosa MF, ProvinceMA, Heiss G, Arnett DK, Myers RH, Pankow JS, Hopkins PN, Borecki IB. Evidence of QTL on 15q21 for High-Density Lipoprotein Cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study. Atherosclerosis 2007;190:232-237

13.                North KE, Franceschini N, Borecki IB, Gu CC, Heiss G, Province MA, Arnett D, Lewis CE, Miller MB, Myers RH, Hunt SC, Freedman BI. Genotype-by-Sex Interaction on Fasting Insulin Concentration: The HyperGEN Study. Diabetes 2007; 56:137-142.  

14.                Tobin JE, Cui J, Wilk JB, Latourelle JC, Laramie JM, McKee AC, Guttman M, Karamohamed S, DeStefano AL, Myers, RH.  Sepiapterin reductase expression is increased in Parkinson’s disease brain tissue. Brain Research 2007; 1139:42-47

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of BU School of Medicine