Intracranial Aneurysms in Finnish Families: Confirmation of Linkage and Refinement of the Interval to Chromosome 19q13.3
| Autor: | Katariina Helin, Monique van der Voet, Juha Jääskeläinen, Moumita Biswas, Doreen M. Dudek, Gerard Tromp, Eira Leinonen, Juha Hernesniemi, Magdalena Skunca, Jane M. Olson, Mika Niemelä, Helena Kuivaniemi, Antti Ronkainen |
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| Jazyk: | angličtina |
| Předmět: |
Genetic Markers
Male Genetics Genetic Linkage Intracranial Aneurysm Locus (genetics) Biology Penetrance Genetic determinism Confidence interval Genetic marker Genetic linkage Sample size determination Report Humans Female Genetic Predisposition to Disease Genetics(clinical) Lod Score Chromosomes Human Pair 19 Nuclear family Finland Genetics (clinical) Microsatellite Repeats |
| Zdroj: | The American Journal of Human Genetics. (3):564-571 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/382285 |
| Popis: | We recently reported a two-stage genomewide screen of 48 sib pairs affected with intracranial aneurysms (IAs) that revealed suggestive linkage to chromosome 19q13, with a LOD score of 2.58. The region supporting linkage spanned approximately 22 cM. Here, we report a follow-up study of the locus at 19q13, with a sample size expanded to 139 affected sib pairs, along with 83 other affected relative pairs (222 affected relative pairs in total). Suggestive linkage was observed in both independent sample sets, and linkage was significant in the combined set at 70 cM (LOD score 3.50; P=.00006) and at 80 cM (LOD score 3.93; P=.00002). Linkage was highly significant at 70 cM (LOD score 5.70; P=.000001) and at 80 cM (LOD score 3.99; P=.00005) when a covariate measuring the number of affected individuals in the nuclear family was included. To evaluate further the contribution to the linkage signal from families with more than two affected relatives, we performed model-based linkage analysis with a recessive model and a range of penetrances, and we obtained maximum linkage at 70 cM (LOD score 3.16; P=.00007) with a penetrance of 0.3. We then estimated location by using GENEFINDER. The most likely location for a gene predisposing to IAs in the Finnish population is in a region with a 95% confidence interval of 11.6 cM (P=.00007) centered 2.0 cM proximal to D19S246. |
| Databáze: | OpenAIRE |
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