Journal article
Results of a high-resolution genome screen of 437 Alzheimer's Disease families
Human molecular genetics, v 12(1), pp 23-32
01 Jan 2003
PMID: 12490529
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (ε4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a ‘highly significant’ linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations—on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22—met criteria for ‘suggestive’ linkage [i.e. two-point lod score (TLS) ≥1.9 and/or multipoint lod score (MLS) ≥2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.
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Details
- Title
- Results of a high-resolution genome screen of 437 Alzheimer's Disease families
- Creators
- Deborah Blacker - Massachusetts General HospitalLars Bertram - Harvard University PressAleister J. Saunders - Harvard University PressThomas J. Moscarillo - Harvard University PressMarilyn S. Albert - Harvard University PressHoward Wiener - University of Alabama at BirminghamRodney T. Perry - University of Alabama at BirminghamJulianne S. Collins - University of Alabama at BirminghamLindy E. Harrell - University of Alabama at BirminghamRodney C.P. Go - University of Alabama at BirminghamAmy Mahoney - Johns Hopkins UniversityTerri Beaty - Johns Hopkins UniversityM. Danielle Fallin - Johns Hopkins UniversityDimitrios Avramopoulos - Johns Hopkins UniversityGary A. Chase - Johns Hopkins UniversityMarshal F. Folstein - Johns Hopkins UniversityMelvin G. McInnis - Johns Hopkins UniversitySusan S. Bassett - Johns Hopkins UniversityKimberly J. Doheny - Center for Inherited Disease Research, USAElizabeth W. Pugh - Center for Inherited Disease Research, USARudolph E. Tanzi - Harvard University PressNIMH Genetics Initiative Alzheime
- Publication Details
- Human molecular genetics, v 12(1), pp 23-32
- Publisher
- Oxford University Press
- Number of pages
- 10
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000180161000003
- Scopus ID
- 2-s2.0-12244296117
- Other Identifier
- 991021448062304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity