scholarly journals Use of local genetic ancestry to assess TOMM40-523′ and risk for Alzheimer disease

2020 ◽  
Vol 6 (2) ◽  
pp. e404 ◽  
Author(s):  
Parker L. Bussies ◽  
Farid Rajabli ◽  
Anthony Griswold ◽  
Daniel A. Dorfsman ◽  
Patrice Whitehead ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Late Onset ◽  
Whole Genome ◽  
Allele Size ◽  
Fragment Analysis ◽  
Race Ethnicity ◽  
Risk Modifier ◽  
Reduced Risk

ObjectiveHere, we re-examine TOMM40-523′ as a race/ethnicity-specific risk modifier for late-onset Alzheimer disease (LOAD) with adjustment for local genomic ancestry (LGA) in Apolipoprotein E (APOE) ε4 haplotypes.MethodsThe TOMM40-523′ size was determined by fragment analysis and whole genome sequencing in homozygous APOE ε3 and APOE ε4 haplotypes of African (AF) or European (EUR) ancestry. The risk for LOAD was assessed within groups by allele size.ResultsThe TOMM40-523′ length did not modify risk for LOAD in APOE ε4 haplotypes with EUR or AF LGA. Increasing length of TOMM40-523′ was associated with a significantly reduced risk for LOAD in EUR APOE ε3 haplotypes.ConclusionsAdjustment for LGA confirms that TOMM40-523′ cannot explain the strong differential risk for LOAD between APOE ε4 with EUR and AF LGA. Our study does confirm previous reports that increasing allele length of the TOMM40-523′ repeat is associated with decreased risk for LOAD in carriers of homozygous APOE ε3 alleles and demonstrates that this effect is occurring in those individuals with the EUR LGA APOE ε3 allele haplotype.

scholarly journals Rare ABCA7 variants in 2 German families with Alzheimer disease

2018 ◽  
Vol 4 (2) ◽  
pp. e224 ◽  
Author(s):  
Patrick May ◽  
Sabrina Pichler ◽  
Daniela Hartl ◽  
Dheeraj R. Bobbili ◽  
Manuel Mayhaus ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rare Variants ◽  
Late Onset ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Pathogenic Variants ◽  
Genome Wide

ObjectiveThe aim of this study was to identify variants associated with familial late-onset Alzheimer disease (AD) using whole-genome sequencing.MethodsSeveral families with an autosomal dominant inheritance pattern of AD were analyzed by whole-genome sequencing. Variants were prioritized for rare, likely pathogenic variants in genes already known to be associated with AD and confirmed by Sanger sequencing using standard protocols.ResultsWe identified 2 rare ABCA7 variants (rs143718918 and rs538591288) with varying penetrance in 2 independent German AD families, respectively. The single nucleotide variant (SNV) rs143718918 causes a missense mutation, and the deletion rs538591288 causes a frameshift mutation of ABCA7. Both variants have previously been reported in larger cohorts but with incomplete segregation information. ABCA7 is one of more than 20 AD risk loci that have so far been identified by genome-wide association studies, and both common and rare variants of ABCA7 have previously been described in different populations with higher frequencies in AD cases than in controls and varying penetrance. Furthermore, ABCA7 is known to be involved in several AD-relevant pathways.ConclusionsWe conclude that both SNVs might contribute to the development of AD in the examined family members. Together with previous findings, our data confirm ABCA7 as one of the most relevant AD risk genes.

O3-13-01: Whole genome sequencing of late-onset Alzheimer's disease patients from genetic isolate

2015 ◽  
Vol 11 (7S_Part_5) ◽  
pp. P250-P251
Author(s):  
Anastasia Grigorenko ◽  
Fedor Gusev ◽  
Denis Reshetov ◽  
Tatiana Andreeva ◽  
Lev Shagam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Late Onset ◽  
Whole Genome ◽  
Genetic Isolate

scholarly journals P4-097: RARE VARIANTS IN FAMILIAL LATE-ONSET ALZHEIMER'S DISEASE IDENTIFIED FROM LARGE SCALE WHOLE GENOME SEQUENCING

2019 ◽  
Vol 15 ◽  
pp. P1312-P1312
Author(s):  
Badri N. Vardarajan ◽  
James Jaworski ◽  
Gary W. Beecham ◽  
Sandra Barral ◽  
Dolly Reyes-Dumeyer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Large Scale ◽  
Rare Variants ◽  
Late Onset ◽  
Whole Genome

scholarly journals Whole genome sequencing of Caribbean Hispanic families with late-onset Alzheimer's disease

2018 ◽  
Vol 5 (4) ◽  
pp. 406-417 ◽  
Author(s):  
Badri N. Vardarajan ◽  
Sandra Barral ◽  
James Jaworski ◽  
Gary W. Beecham ◽  
Elizabeth Blue ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Late Onset ◽  
Whole Genome ◽  
Hispanic Families

scholarly journals Multiplex Fragment analysis detects all COVID-19 variants of concern

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S138-S138
Author(s):  
J A SoRelle ◽  
A Clark ◽  
Z Wang ◽  
J Park
Keyword(s):  
New York ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Fragment Analysis ◽  
Deletion Mutations ◽  
Percent Agreement ◽  
Indian Origin ◽  
Allele Specific ◽  
Variant Analysis

Abstract Introduction/Objective The majority of tracking methods have employed whole genome sequencing, which can be very expensive and time consuming. An alternative method has been to use genotyping of specific mutations to identify variants. However, tracking SARS-CoV-2 variants by targeted methods has been a moving target. Most methods only multiplex four targets per reaction, but we have multiplexed 8 targets in a single tube using fragment analysis. Methods/Case Report Fluorescently labeled primers targeted a combination of insertion/ deletion mutations and single nucleotide mutations. The PCR amplified products, amplicons, were separated by capillary electrophoresis. Primers were designed to detect changes in size indicative of insertion or deletion mutations including: ORF1A:Del3675_3677, S:Del69_70, S:Del144, S:Del157_158, S:Del242_244, ORF8:Del119_120, and ORF8:ins28269-28273. Allele-specific primers were designed to detect both the wild-type and mutated versions of S:N501Y, S:E484K, and S:L452R. Residual nasopharyngeal and nasal specimens testing positive for SARS-CoV-2 by RT-PCR or isothermal amplification (IDnow) methods were selected from May 1- June 24, 2021. Variant analysis was performed by multiplex targeted PCR and whole genome sequencing in parallel on the same specimens to determine positive percent agreement. Results (if a Case Study enter NA) Variant analysis was performed on 250 specimens detecting each of the major variants of concern Alpha (B.1.1.7, U.K. origin, n= 108), Beta (B.1.351, South Africa origin, n=3), Gamma (P.1, Brazil origin, n=12), Delta (B.1.617.2, Indian origin, n=17), and Iota (B.1.526, New York, n=5). Some specimens with low viral load were detected by only PCR (n=18), only WGS (n=41), or neither (n=20). Overall positive percent agreement was 95% (163/171). Conclusion This adjustable method robustly and accurately identifies COVID-19 VOCs utilizing a platform amenable to multiple targets (20-40 targets ranging from 100-500b.p. across four fluorescent channels) using equipment commonly found in routine molecular pathology laboratories. Future directions include adjusting targets to detect new variants.

P1-156: GENE-BASED ANALYSES IN WHOLE GENOME SEQUENCING OF FAMILIAL LATE-ONSET ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_6) ◽  
pp. P336-P337
Author(s):  
Badri N. Vardarajan ◽  
Sandra Barral ◽  
James Jaworski ◽  
Gary W. Beecham ◽  
Elizabeth Blue ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Late Onset ◽  
Whole Genome

O1-09-03: Whole Genome Sequencing in Familial Late-Onset Alzheimer’s Disease Identifies Variations in TTC3 and FSIP2

2016 ◽  
Vol 12 ◽  
pp. P197-P197
Author(s):  
Gary W. Beecham ◽  
Badri N. Vardarajan ◽  
Elizabeth Blue ◽  
Sandra Barral ◽  
Jonathan L. Haines ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Late Onset ◽  
Whole Genome
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