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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mineharu
Youhei
Y
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, Japan.
Inoue
Kayoko
K
Inoue
Sumiko
S
Yamada
Shigeki
S
Nozaki
Kazuhiko
K
Hashimoto
Nobuo
N
Koizumi
Akio
A
D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D016678:Genome; D005838:Genotype; D006801:Humans; D002532:Intracranial Aneurysm / Q000208:ethnology / Q000235:genetics*; D007564:Japan; D008297:Male; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
D005819:Genetic Markers