title: Identification of a genetic locus for familial atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrillation, the most common sustained cardiac-rhythm disturbance, affects over 2 million Americans and accounts for one third of all strokes in patients over 65 years of age. The molecular basis for atrial fibrillation is unknown, and palliative therapy is used to control the ventricular rate and prevent systemic emboli. We identified a family of 26 members of whom 10 had atrial fibrillation which segregated as an autosomal dominant disease. We subsequently identified two additional families in which the disease was linked to the same locus.
  
  
  METHODS
  We screened the human genome with 300 polymorphic dinucleotide-repeat markers using an unconventional strategy of pooling the DNA samples into two groups (affected and unaffected), which reduced the sample size by approximately 90 percent, before performing linkage analysis to map the locus. This made it possible to identify potential loci within a few weeks.
  
  
  RESULTS
  The lod scores for markers D10S569 and D10S607, located at 10q22-q24, were 3.60 in Family 1. The disease locus in Families 2 and 3 was also linked to the same markers, with lod scores of 6.02 and 5.35 for markers D10S569 and D10S607, respectively, when data on all three families were combined. Haplotype analysis of the three families showed that the locus was between D10S1694 and D10S1786, an interval of 11.3 centimorgans.
  
  
  CONCLUSIONS
  Identification of the gene for familial atrial fibrillation will help to elucidate the molecular basis of the disease and provide insights into acquired forms. The strategy of pooling DNA samples for analysis is more time and cost effective than conventional screening and should accelerate the process of gene mapping in the future.
authors.affiliation: Department of Cardiology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Brugada
authors.forename: T
authors.initials: T
authors.lastname: Tapscott
authors.forename: G Z
authors.initials: GZ
authors.lastname: Czernuszewicz
authors.forename: A J
authors.initials: AJ
authors.lastname: Marian
authors.forename: A
authors.initials: A
authors.lastname: Iglesias
authors.forename: L
authors.initials: L
authors.lastname: Mont
authors.forename: J
authors.initials: J
authors.lastname: Brugada
authors.forename: J
authors.initials: J
authors.lastname: Girona
authors.forename: A
authors.initials: A
authors.lastname: Domingo
authors.forename: L L
authors.initials: LL
authors.lastname: Bachinski
authors.forename: R
authors.initials: R
authors.lastname: Roberts
mesh_terms: D000328:Adult; D001281:Atrial Fibrillation / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002879:Chromosomes, Human, Pair 10; D018900:Dinucleotide Repeats; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005784:Gene Amplification; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D005819:Genetic Markers