An autosomal genomic screen for dementia in an extended Amish family
| Autor: | Kathleen A. Welsh-Bohmer, Charles E. Jackson, William K. Scott, P. C. Gaskell, Yujun Shao, J. B. Rimmler, Allison E. Ashley-Koch, Margaret A. Pericak-Vance, Jonathan L. Haines |
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| Rok vydání: | 2004 |
| Předmět: |
Apolipoprotein E
Gerontology Models Molecular Genetic Linkage Population Apolipoprotein E4 Apolipoproteins E Genetic linkage Alzheimer Disease Ethnicity Medicine Dementia Chromosomes Human Humans Genetic Predisposition to Disease Genetic Testing Allele education Genetic testing Genetics Family Health education.field_of_study medicine.diagnostic_test business.industry General Neuroscience Chromosome Mapping medicine.disease Human genetics Pedigree Genetic marker Female Lod Score business |
| Zdroj: | Neuroscience letters. 379(3) |
| ISSN: | 0304-3940 |
| Popis: | Apolipoprotein E (APOE) is the only universally confirmed susceptibility gene for late-onset Alzheimer disease (LOAD), although many loci are believed to modulate LOAD risk. The genetic homogeneity of isolated populations, such as the Amish, potentially provide increased power to identify LOAD susceptibility genes. Population homogeneity in these special populations may reduce the total number of susceptibility genes contributing to the complex disorder, thereby increasing the ability to identify any one susceptibility gene. Dementia in the Amish is clinically indistinguishable from LOAD in the general population. Previous studies in the Amish demonstrated a significantly decreased frequency of the APOE-4 susceptibility allele, but significant familial clustering of dementia [M.A. Pericak-Vance, C.C. Johnson, J.B. Rimmler, A.M. Saunders, L.C. Robinson, E.G. D'Hondt, C.E. Jackson, J.L. Haines, Alzheimer's disease and apolipoprotein E-4 allele in an Amish population, Ann. Neurol. 39 (1996) 700-704]. These data suggested that a genetic etiology independent of APOE may underlie the dementia observed in this population. In the present analysis, we focused on a large, multiplex, inbred Amish family (24 sampled individuals; 10 of whom are affected). We completed a genomic screen to identify novel LOAD loci (n=316 genetic markers), using both model-dependent "affecteds-only" analysis (dominant and recessive) and model-independent affected relative pair analysis. Interesting results (lod>1.5 or p |
| Databáze: | OpenAIRE |
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