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| FAMILIAL ALZHEIMERS-DISEASE IN KINDREDS WITH MISSENSE MUTATIONS IN A GENE ON CHROMOSOME-1 RELATED TO THE ALZHEIMERS-DISEASE TYPE-3 GENE |
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| Author(s): ROGAEV EI, SHERRINGTON R, ROGAEVA EA, LEVESQUE G, IKEDA M, LIANG Y, CHI H, LIN C, HOLMAN K, TSUDA T, MAR L, SORBI S, NACMIAS B, PIACENTINI S, AMADUCCI L, CHUMAKOV I, COHEN D, LANNFELT L, FRASER PE, ROMMENS JM, STGEORGEHYSLOP PH |
| Source: NATURE Volume: 376 Issue: 6543 Pages: 775-778 Published: AUG 31 1995 |
| Times Cited: 1,066 References: 9 |
| Abstract: WE report the cloning of a novel gene (E5-1) encoded on chromosome 1 which has substantial nucleotide and amino-acid sequence similarity to the S182 gene on chromosome 14q24.3. Mutations, including three new missense mutations in the S182 gene, are associated with the AD3 subtype of early-onset familial Alzheimer's disease (AD)(1). Both the E5-1 and the S182 proteins are predicted to be integral membrane proteins with seven membrane-spanning domains, and a large exposed loop between the sixth and seventh transmembrane domains. Analysis of the nucleotide sequence of the open reading frame (ORF) of the E5-1 gene led to the discovery of two missense substitutions at conserved amino-acid residues in affected members of pedigrees with a form of familial AD that has a later age of onset than the AD3 subtype (50-70 years versus 30-60 years for AD3). These observations imply that the E5-1 gene on chromosome 1 and the S182 gene on chromosome 14q24.3 are members of a family of genes (presenilins) with related functions, and indicates that mutations in conserved residues of E5-1 could also play a role in the genesis of AD. Our results also indicate that still other AD susceptibility genes exist. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV TORONTO, CTR RES NEURODEGENERAT DIS, DEPT MED NEUROL, TORONTO, ON M5S 1A8 CANADA
2. UNIV TORONTO, CTR RES NEURODEGENERAT DIS, DEPT MED BIOPHYS, TORONTO, ON M5S 1A8 CANADA
3. TORONTO HOSP, DEPT MED, DIV NEUROL, TORONTO, ON M5S 1A8 CANADA
4. UNIV TORONTO, HOSP SICK CHILDREN, RES INST, TORONTO, ON M5S 1A8 CANADA
5. UNIV TORONTO, DEPT MED & MOLEC GENET, TORONTO, ON M5S 1A8 CANADA
6. UNIV FLORENCE, DEPT NEUROL & PSYCHIAT, FLORENCE, ITALY
7. CTR ETUD POLYMORPHISME HUMAIN, F-75010 PARIS, FRANCE
8. KAROLINSKA INST, HUDDINGE HOSP, DEPT CLIN NEUROSCI GERIATR MED, S-14186 HUDDINGE, SWEDEN |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: RR836 |
| ISSN: 0028-0836 |
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