| | |  | | | | Record from Web of Science® | | | | | | |
| ASSESSMENT OF AMYLOID BETA-PROTEIN PRECURSOR GENE-MUTATIONS IN A LARGE SET OF FAMILIAL AND SPORADIC ALZHEIMER-DISEASE CASES |
|
|
| Author(s): TANZI RE, VAULA G, ROMANO DM, MORTILLA M, HUANG TL, TUPLER RG, WASCO W, HYMAN BT, HAINES JL, JENKINS BJ, KALAITSIDAKI M, WARREN AC, MCINNIS MC, ANTONARAKIS SE, KARLINSKY H, PERCY ME, CONNOR L, GROWDON J, CRAPPERMCLACHLAN DR, GUSELLA JF, STGEORGEHYSLOP PH |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 51 Issue: 2 Pages: 273-282 Published: AUG 1992 |
| Times Cited: 143 References: 42 |
| Abstract: A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including FAD4, a large kindred showing highly suggestive evidence for linkage of the disorder to chromosome 21. In case the apparent APP crossover in FAD4 actually represented an intragenic recombination event or segregation of different mutations in different family branches, we have performed a more detailed assessment of APP as a candidate gene in this family. The entire coding region of the APP gene was sequenced for FAD4 and for FAD1, a second large kindred. No mutations were found, indicating that, in at least one chromosome 21-linked FAD pedigree, the gene defect is not accounted for by a mutation in the known coding region of the APP gene. A total of 25 well-characterized early- and late-onset FAD pedigrees were typed for genetic linkage to APP, to assess the percentage of FAD families predicted to carry mutations in the APP gene. None of the FAD families yielded positive lod scores at a recombination fraction of 0.0. To estimate the overall prevalence of FAD-associated mutations in the beta-A4 domain of APP, we sequenced exons 16 and 17 in 30 (20 early- and 10 late-onset) FAD kindreds and in 11 sporadic AD cases, and we screened 56 FAD kindreds and 81 cases of sporadic AD for the presence of the originally reported FAD-associated mutation, APP717 Val --> Ile (by BclI digestion). No APP gene mutations were found in any of the FAD families or sporadic-AD samples examined in this study, suggesting that the mutations in exons 16 and 17 are a rare cause of FAD. Overall, these data suggest that APP gene mutations account for a very small portion of FAD. |
| Document Type: Article |
| Language: English |
Addresses:
1. MASSACHUSETTS GEN HOSP, DEPT NEUROL, MOLEC NEUROGENET LAB, BOSTON, MA 02114 USA
2. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA
3. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA
4. UNIV TORONTO, DEPT MED, TORONTO M5S 1A1, ONTARIO CANADA
5. UNIV TORONTO, DEPT NEUROL, TORONTO M5S 1A1, ONTARIO CANADA
6. UNIV TORONTO, DEPT PSYCHIAT, TORONTO M5S 1A1, ONTARIO CANADA
7. UNIV TORONTO, SURREY PL CTR OBSTET & GYNECOL, TORONTO M5S 1A1, ONTARIO CANADA
8. JOHNS HOPKINS UNIV, SCH MED, CTR MED GENET, BALTIMORE, MD 21205 USA
9. JOHNS HOPKINS UNIV, SCH MED, DEPT PSYCHIAT, BALTIMORE, MD 21205 USA |
| Publisher: UNIV CHICAGO PRESS, 5720 S WOODLAWN AVE, CHICAGO, IL 60637 |
| Subject Category: Genetics & Heredity |
| IDS Number: JF776 |
| ISSN: 0002-9297 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |