دورية أكاديمية
أعرض في EDS

Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function.

التفاصيل البيبلوغرافية
العنوان: Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function.
المؤلفون: Cukier HN; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA., Kunkle BK; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Hamilton KL; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Rolati S; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Kohli MA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Whitehead PL; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Jaworski J; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA., Vance JM; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Cuccaro ML; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Carney RM; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; Mental Health and Behavioral Sciences Service, Miami Veterans Affairs, Miami, FL, USA., Gilbert JR; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Farrer LA; Departments of Medicine, Neurology, Ophthalmology, Genetics and Genomics, Epidemiology and Biostatistics, Boston University, Boston, MA, USA., Martin ER; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Beecham GW; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA., Haines JL; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Pericak-Vance MA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.; John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
المصدر: Journal of Alzheimer's disease & Parkinsonism [J Alzheimers Dis Parkinsonism] 2017 Aug; Vol. 7 (4). Date of Electronic Publication: 2017 Jul 31.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: OMICS Pub. Group Country of Publication: United States NLM ID: 101587593 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2161-0460 (Print) NLM ISO Abbreviation: J Alzheimers Dis Parkinsonism Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Sunnyvale, Calif. : OMICS Pub. Group
مستخلص: Objective: Alzheimer's disease (AD) is a neurodegenerative disorder for which more than 20 genetic loci have been implicated to date. However, studies demonstrate not all genetic factors have been identified. Therefore, in this study we seek to identify additional rare variants and novel genes potentially contributing to AD.
Methods: Whole exome sequencing was performed on 23 multi-generational families with an average of eight affected subjects. Exome sequencing was filtered for rare, nonsynonymous and loss-of-function variants. Alterations predicted to have a functional consequence and located within either a previously reported AD gene, a linkage peak (LOD>2), or clustering in the same gene across multiple families, were prioritized.
Results: Rare variants were found in known AD risk genes including AKAP9, CD33, CR1, EPHA1, INPP5D, NME8, PSEN1, SORL1, TREM2 and UNC5C . Three families had five variants of interest in linkage regions with LOD>2. Genes with segregating alterations in these peaks include CD163L1 and CLECL1 , two genes that have both been implicated in immunity, CTNNA1 , which encodes a catenin in the cerebral cortex and MIEF1 , a gene that may induce mitochondrial dysfunction and has the potential to damage neurons. Four genes were identified with alterations in more than one family include PLEKHG5 , a gene that causes Charcot-Marie-Tooth disease and THBS2 , which promotes synaptogenesis.
Conclusion: Utilizing large families with a heavy burden of disease allowed for the identification of rare variants co-segregating with disease. Variants were identified in both known AD risk genes and in novel genes.
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معلومات مُعتمدة: R01 AG019085 United States AG NIA NIH HHS; U01 AG032984 United States AG NIA NIH HHS; P30 AG013846 United States AG NIA NIH HHS; R01 AG028786 United States AG NIA NIH HHS; U24 AG026395 United States AG NIA NIH HHS; R01 AG041797 United States AG NIA NIH HHS; R01 AG048927 United States AG NIA NIH HHS; P20 MD000546 United States MD NIMHD NIH HHS; R01 AG027944 United States AG NIA NIH HHS; R01 AG025259 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: Alzheimer’s disease; dominant inheritance; linkage; multiplex; whole exome sequencing
تواريخ الأحداث: Date Created: 20171128 Latest Revision: 20220408
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5698805
DOI: 10.4172/2161-0460.1000355
PMID: 29177109
قاعدة البيانات: MEDLINE
الوصف
تدمد:2161-0460
DOI:10.4172/2161-0460.1000355