title: Mapping a Mendelian form of intracranial aneurysm to 1p34.3-p36.13.
abstract: The identification of pathways that underlie common disease has been greatly impacted by the study of rare families that segregate single genes with large effect. Intracranial aneurysm is a common neurological problem; the rupture of these aneurysms constitutes a frequently catastrophic neurologic event. The pathogenesis of these aneurysms is largely unknown, although genetic and environmental factors are believed to play a role. Previous genomewide studies in affected relative pairs have suggested linkage to several loci, but underlying genes have not been identified. We have identified a large kindred that segregates nonsyndromic intracranial aneurysm as a dominant trait with high penetrance. Genomewide analysis of linkage was performed using a two-stage approach: an analysis of ~10,000 single-nucleotide polymorphisms in the 6 living affected subjects, followed by the genotyping of simple tandem repeats across resulting candidate intervals in all 23 kindred members. Analysis revealed significant linkage to a single locus, with a LOD score of 4.2 at 1p34.3-p36.13 under a dominant model with high penetrance. These findings identify a Mendelian form of intracranial aneurysm and map the location of the underlying disease locus.
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Nahed
authors.forename: Askin
authors.initials: A
authors.lastname: Seker
authors.forename: Bulent
authors.initials: B
authors.lastname: Guclu
authors.forename: Ali K
authors.initials: AK
authors.lastname: Ozturk
authors.forename: Karin
authors.initials: K
authors.lastname: Finberg
authors.forename: Abigail A
authors.initials: AA
authors.lastname: Hawkins
authors.forename: Michael L
authors.initials: ML
authors.lastname: DiLuna
authors.forename: Matthew
authors.initials: M
authors.lastname: State
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
mesh_terms: D000328:Adult; D000367:Age Factors; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide