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Familial atrial fibrillation is a genetically heterogeneous disorder

Dawood Darbar, MD^*, Kathleen J. Herron, BA^*, Jeffrey D. Ballew, MSc^*, Arshad Jahangir, MD^*, Bernard J. Gersh, MBChB, DPhil, FACC^*, Win-K. Shen, MD, FACC^*, Stephen C. Hammill, MD, FACC^*, Douglas L. Packer, MD, FACC^* and Timothy M. Olson, MD^*,*

^* Departments of Medicine, Division of Cardiovascular Diseases, Rochester, Minnesota, USA
Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, USA

View larger version (44K): [in a new window]   Figure 1 Haplotype analyses of three pedigrees with familial atrial fibrillation (AF). Pedigree symbols represent the following traits: circles = females; squares = males; diagonal lines = deceased; filled = AF; hatched = uncertain; empty = asymptomatic and no documented AF. Haplotypes are comprised of genotypes for eight tightly linked markers spaced 1 to 3 centiMorgans (cM) apart. D10S1694 and D10S1786 define the centromeric and telomeric boundaries, respectively, of a previously reported familial AF locus on chromosome 10q22-q24. Double recombination events between adjacent markers were assumed not to have occurred, and haplotypes of deceased individuals were inferred when possible. The patriarchal or matriarchal haplotype inherited by the majority of individuals with AF within each family is boxed, illustrating at least one affected individual who does not inherit this haplotype. These data exclude a disease gene for familial AF at this locus. FAF = multi-generation families with autosomal dominant atrial fibrillation.

View larger version (58K): [in a new window]   Figure 2 Haplotype analyses of a pedigree with familial atrial fibrillation (AF) and early features of dilated cardiomyopathy. Haplotypes were constructed at a locus for familial AF (a) and loci for familial dilated cardiomyopathy, sinus node dysfunction, conduction system disease, and AF on chromosomes 3p22-p25 (b) and 1q21 (c), where the lamin A/C gene is located. The affected individuals do not inherit the same haplotype, excluding a disease gene at these loci. FAF = multi-generation families with autosomal dominant atrial fibrillation. Continued on next page