title: Haplotype analysis of the ETM2 locus in familial essential tremor.
abstract: The objective of this study was to analyze a sample of unrelated individuals with autosomal dominant essential tremor (ET) for a genetic association with loci in a candidate region (ETM2) on chromosome 2p24.1 that harbors a disease gene for ET. ET is a common movement disorder that is genetically linked to ETM2 in four large families. It is unknown whether this candidate locus is associated with dominantly inherited ET in other individuals. Based on information from previous genetic linkage studies, a linkage disequilibrium study was designed to compare individuals with a family history of ET (n=45) with normal controls (n=70). Three unreported dinucleotide polymorphic loci (etm1240, etm1231, and etm1234) were identified on a physical map of the ETM2 interval in a region of no recombination. The study sample was tested for allele frequency differences by the CLUMP program and haplotypes were analyzed by the FASTEHPLUS program. The allele frequencies were significantly different between ET cases and the control samples for the loci etm1231 (P< or =0.0419) and etm1234 (P<0.0001). A haplotype formed by the loci etm1231 and etm1234 occurred with a frequency of 29% in cases (n=45) and 9% in a white newborn sample (P<0.0001, n=35). The haplotype was not found in normal individuals older than 60 years without tremor (P=0.0063, n=35). This study provides evidence that an ancestral haplotype on chromosome 2p24.1 segregates with the ET disease phenotype in individuals with a family history of the disorder and will facilitate the search for a causative gene.
authors.affiliation: Center for Human Genetics and Child Neurology, Mid-Hudson Family Health Institute, 279 Main Street, Suite 203A, New Paltz, NY 12561, USA. jhiggins@fpinstitute.org
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Higgins
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: Roni Q
authors.initials: RQ
authors.lastname: Lombardi
authors.forename: Joanna
authors.initials: J
authors.lastname: Pucilowska
authors.forename: Eng King
authors.initials: EK
authors.lastname: Tan
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Melanie U
authors.initials: MU
authors.lastname: Ruszczyk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D020329:Essential Tremor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged
chemical_list: D005819:Genetic Markers