Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers.
Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers.
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DOI：
10.1002/humu.22167
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发表时间：
2012-12
期刊：
影响因子：
3.9
通讯作者：
Lopera, Francisco
中科院分区：
文献类型：
--
作者：
Lalli, Matthew A.;Garcia, Gloria;Madrigal, Lucia;Arcos-Burgos, Mauricio;Arcila, Mary Luz;Kosik, Kenneth S.;Lopera, Francisco
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 age-at-onset 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.
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DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
7
作者：
Gusev, Alexander;Lowe, Jennifer K.;Pe'er, Itsik
通讯作者：
Pe'er, Itsik
影响因子：
20.3
作者：
Aasheim, HC;Delabie, J;Finne, EF
通讯作者：
Finne, EF
DOI：
10.1073/pnas.93.22.12593
发表时间：
1996-10-29
影响因子：
11.1
作者：
Miller, KG;Alfonso, A;Rand, JB
通讯作者：
Rand, JB
影响因子：
25
作者：
Cheng, Jason S.;Dubal, Dena B.;Kim, Daniel H.;Legleiter, Justin;Cheng, Irene H.;Yu, Gui-Qiu;Tesseur, Ina;Wyss-Coray, Tony;Bonaldo, Paolo;Mucke, Lennart
通讯作者：
Mucke, Lennart