دورية أكاديمية
أعرض في EDS

Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers.

التفاصيل البيبلوغرافية
العنوان: Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers.
المؤلفون: Lalli MA; Neuroscience Research Institute, University of California at Santa Barbara, CA, USA., Garcia G, Madrigal L, Arcos-Burgos M, Arcila ML, Kosik KS, Lopera F
المصدر: Human mutation [Hum Mutat] 2012 Dec; Vol. 33 (12), pp. 1630-4. Date of Electronic Publication: 2012 Aug 10.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 9215429 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-1004 (Electronic) Linking ISSN: 10597794 NLM ISO Abbreviation: Hum Mutat Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Wiley-Liss, c1992-
مواضيع طبية MeSH: Alzheimer Disease/*genetics , Chromosomes, Human, Pair 1/*genetics , Chromosomes, Human, Pair 16/*genetics, Age Factors ; Chromosome Mapping ; Gene Frequency ; Genetic Association Studies ; Genome, Human ; Humans ; Mutation, Missense ; Open Reading Frames/genetics ; Sequence Analysis, DNA
مستخلص: Identifying genes that modify the age at onset (AAO) of Alzheimer disease and targeting them pharmacologically represent a potential treatment strategy. In this exploratory study, we sequenced the complete genomes of six individuals with familial Alzheimer disease due to the autosomal dominant mutation p.Glu280Ala in PSEN1 (MIM# 104311; NM_000021.3:c.839A>C). The disease and its AAO are highly heritable, motivating our search for genetic variants that modulate AAO. The median AAO of dementia in carriers of the mutant allele is 49 years. Extreme phenotypic outliers for AAO in this genetically isolated population with limited environmental variance are likely to harbor onset modifying genetic variants. A narrow distribution of AAO in this kindred suggests large effect sizes of genetic determinants of AAO in these outliers. Identity by descent (IBD) analysis and a combination of bioinformatics filters have suggested several candidate variants for AAO modifiers. Future work and replication studies on these variants may provide mechanistic insights into the etiopathology of Alzheimer disease.
(© 2012 Wiley Periodicals, Inc.)
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معلومات مُعتمدة: R01 AG029802 United States AG NIA NIH HHS; R21 AG024063 United States AG NIA NIH HHS
تواريخ الأحداث: Date Created: 20120726 Date Completed: 20130416 Latest Revision: 20211021
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3496074
DOI: 10.1002/humu.22167
PMID: 22829467
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-1004
DOI:10.1002/humu.22167