Model-based linkage analyses confirm chromosome 19q13.3 as a susceptibility locus for intracranial aneurysm

• Published in: Stroke (1970) Vol. 38; no. 4; pp. 1174 - 1178
• Main Authors: MINEHARU, Youhei, INOUE, Kayoko, INOUE, Sumiko, YAMADA, Shigeki, NOZAKI, Kazuhiko, HASHIMOTO, Nobuo, KOIZUMI, Akio
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-04-2007
• Subjects: Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 19 - genetics; Diseases of the nervous system; DNA Mutational Analysis; Female; Gene Frequency; Genetic Linkage - genetics; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Genome; Genotype; Humans; Intracranial Aneurysm - ethnology; Intracranial Aneurysm - genetics; Japan; Male; Medical sciences; Models, Genetic; Mutation - genetics; Neurology; Neuropharmacology; Neuroprotective agent; Pedigree; Pharmacology. Drug treatments; Phenotype; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Vascular diseases and vascular malformations of the nervous system; Japan; Stroke; Nervous system diseases; Cardiovascular disease; autosomal-dominant; linkage; Cerebral disorder; Vascular disease; familial; genetics; intracranial aneurysm; Central nervous system disease; Genetic linkage; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000259657.73682.03

In previous studies of familial intracranial aneurysm (IA), parametric linkage analyses have been undertaken for five unrelated families, four providing maximum logarithm of odds (LOD) scores with dominant models and one with a recessive model. Each family was linked to a distinct locus, indicating locus heterogeneity. This study aimed to examine whether Japanese IA families consistent with autosomal-dominant mode of inheritance support linkage to these loci.
We performed genomewide linkage analysis using the GENEHUNTER program. Affected-only parametric linkage analysis was used for 41 affected members in nine unrelated IA families with dominant models, which were selected from 29 families used for a nonparametric (model-free) linkage analysis in our previous study.
We failed to support the linkage to previously reported autosomal-dominant loci. Instead, we found linkage to chromosome 19q13.3 with a maximum multipoint LOD score of 4.10. The LOD-1 interval (regions with LOD scores of >1) was 8.0 cM between D19S198 and D19S902.
A genomewide scan for IA families with dominant models in Japan confirmed the locus at chromosome 19q13.3, which has also been reported as a candidate locus in a Finnish population.