Search for intracranial aneurysm susceptibility gene(s) using Finnish families
| Autor: | Lee-Lian Kim, Helena Kuivaniemi, Juha Hernesniemi, Jane M. Olson, Antti Ronkainen, Sompong Vongpunsawad, Markku Ryynänen, Gerard Tromp |
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| Rok vydání: | 2002 |
| Předmět: |
Genetics
lcsh:Internal medicine lcsh:QH426-470 Autosomal dominant polycystic kidney disease Chromosome 030204 cardiovascular system & hematology Biology medicine.disease Disease cluster Human genetics 3. Good health lcsh:Genetics 03 medical and health sciences 0302 clinical medicine Genetic linkage Relative risk medicine Genetics(clinical) Sibling lcsh:RC31-1245 030217 neurology & neurosurgery Genetics (clinical) Research Article Cause of death |
| Zdroj: | BMC Medical Genetics BMC Medical Genetics, Vol 3, Iss 1, p 7 (2002) |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/1471-2350-3-7 |
| Popis: | Background Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci. Methods We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect. Results Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6. Conclusions Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests. |
| Databáze: | OpenAIRE |
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