Haplotype analysis of the ETM2 locus in familial essential tremor

Joseph J. Higgins, Joseph Jankovic, Roni Q. Lombardi, Joanna Pucilowska, Eng King Tan, Tetsuo Ashizawa, Melanie U. Ruszczyk

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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≤0.0419) and etml234 (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.

Original languageEnglish (US)
Pages (from-to)185-189
Number of pages5
Issue number4
StatePublished - Aug 2003


  • Essential tremor
  • Genetic markers
  • Haplotypes
  • Human chromosomes
  • Linkage disequilibrium
  • Pair 2

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience


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