scholarly journals Copy Number Variation Identification on 3,800 Alzheimer’s Disease Whole Genome Sequencing Data from the Alzheimer’s Disease Sequencing Project

2021 ◽  
Vol 12 ◽  
Author(s):  
Wan-Ping Lee ◽  
Albert A. Tucci ◽  
Mitchell Conery ◽  
Yuk Yee Leung ◽  
Amanda B. Kuzma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Copy Number Variation ◽  
Copy Number ◽  
Whole Genome Sequence ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Sequencing Project ◽  
Number Variation

Alzheimer’s Disease (AD) is a progressive neurologic disease and the most common form of dementia. While the causes of AD are not completely understood, genetics plays a key role in the etiology of AD, and thus finding genetic factors holds the potential to uncover novel AD mechanisms. For this study, we focus on copy number variation (CNV) detection and burden analysis. Leveraging whole-genome sequence (WGS) data released by Alzheimer’s Disease Sequencing Project (ADSP), we developed a scalable bioinformatics pipeline to identify CNVs. This pipeline was applied to 1,737 AD cases and 2,063 cognitively normal controls. As a result, we observed 237,306 and 42,767 deletions and duplications, respectively, with an average of 2,255 deletions and 1,820 duplications per subject. The burden tests show that Non-Hispanic-White cases on average have 16 more duplications than controls do (p-value 2e-6), and Hispanic cases have larger deletions than controls do (p-value 6.8e-5).

The average copy number variation (CNVA) of chromosome fragments is a potential surrogate marker for TMB in predicting responses to immunotherapy in Non-small cell lung cancer

2020 ◽  
Author(s):  
Yuan yuan Lei ◽  
Guo chao Zhang ◽  
Chao qi Zhang ◽  
li yan xue ◽  
Zhen lin Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Copy Number Variation ◽  
Genomic Instability ◽  
Genome Sequencing ◽  
Copy Number ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Number Variation ◽  
Average Copy

Abstract Background: Genomic instability plays a large role in the process of cancer. Tumor mutational burden (TMB) is closely related to immunotherapy outcome and is an important manifestation of genomic instability. However, the cost of TMB detection is extremely high, which limits the use of TMB in clinical practice. Another new indicator of genome instability, CNVA (the average copy number variation) which calculates the changes of 0.5 Mb chromosomal fragments, requires extremely low sequencing depth, and is expected to replace TMB as a new marker of immune efficacy.Methods: A total of 50 samples (23 of which came from patients who received immunotherapy) were subjected to low-depth (10X) chromosome sequencing on the MGI platform. CNVA was calculated by the formula avg (abs (copy number-2)). Then, we analyzed the relationship between CNVA and immune infiltration or immunotherapy efficacy. In addition, through the analysis of whole genome sequencing data of 509 lung adenocarcinoma in the TCGA database, we compared CNVA with classic marker TMB to evaluate the value of CNVA as an immune evaluation index.Results: Compared with the low CNVA group, the high CNVA group had higher expression of PD-L1, CD39 and CD19, and more infiltration of CD8 + T cells and CD3 + T cells. Among the 23 patients treated with immunotherapy, the average CNVA value of the SD (stable disease)/PR (partial response) group was higher than that of the PD (progressive disease) group (P <0.05). The data of whole genome sequencing data of 509 lung adenocarcinomas from TCGA and real-time quantitative PCR results of 22 frozen specimens found that CNVA was more correlated with CD8 and PD-L1 than TMB. In addition, CNVA showed a specific positive correlation with TMB (r = 0.2728, p < 0.0001).Conclusion: CNVA can be a good indicator of immune infiltration and predicting immunotherapy efficacy. With its low cost and potential clinical application for testing, it is expected to become a substitute for TMB.

scholarly journals Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion

2011 ◽  
Vol 108 (46) ◽  
pp. E1128-E1136 ◽  
Author(s):  
R. Xi ◽  
A. G. Hadjipanayis ◽  
L. J. Luquette ◽  
T.-M. Kim ◽  
E. Lee ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Genome Sequencing ◽  
Bayesian Information Criterion ◽  
Copy Number ◽  
Information Criterion ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Number Variation ◽  
Copy Number Variation Detection

Investigation of copy number variation in subjects with major depression based on whole-genome sequencing data

2017 ◽  
Vol 220 ◽  
pp. 38-42 ◽  
Author(s):  
Chenglong Yu ◽  
Bernhard T. Baune ◽  
Ma-Li Wong ◽  
Julio Licinio
Keyword(s):  
Major Depression ◽  
Copy Number Variation ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Number Variation

scholarly journals Insights into dispersed duplications and complex structural mutations from whole genome sequencing 706 families

2020 ◽  
Author(s):  
Christopher W. Whelan ◽  
Robert E. Handsaker ◽  
Giulio Genovese ◽  
Seva Kashin ◽  
Monkol Lek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number Variation ◽  
Copy Number ◽  
De Novo ◽  
Whole Genome ◽  
Sequencing Data ◽  
Number Variation ◽  
Structural Mutations ◽  
Or Gene ◽  
Genomic Locations

AbstractTwo intriguing forms of genome structural variation (SV) – dispersed duplications, and de novo rearrangements of complex, multi-allelic loci – have long escaped genomic analysis. We describe a new way to find and characterize such variation by utilizing identity-by-descent (IBD) relationships between siblings together with high-precision measurements of segmental copy number. Analyzing whole-genome sequence data from 706 families, we find hundreds of “IBD-discordant” (IBDD) CNVs: loci at which siblings’ CNV measurements and IBD states are mathematically inconsistent. We found that commonly-IBDD CNVs identify dispersed duplications; we mapped 95 of these common dispersed duplications to their true genomic locations through family-based linkage and population linkage disequilibrium (LD), and found several to be in strong LD with genome-wide association (GWAS) signals for common diseases or gene expression variation at their revealed genomic locations. Other CNVs that were IBDD in a single family appear to involve de novo mutations in complex and multi-allelic loci; we identified 26 de novo structural mutations that had not been previously detected in earlier analyses of the same families by diverse SV analysis methods. These included a de novo mutation of the amylase gene locus and multiple de novo mutations at chromosome 15q14. Combining these complex mutations with more-conventional CNVs, we estimate that segmental mutations larger than 1kb arise in about one per 22 human meioses. These methods are complementary to previous techniques in that they interrogate genomic regions that are home to segmental duplication, high CNV allele frequencies, and multi-allelic CNVs.Author SummaryCopy number variation is an important form of genetic variation in which individuals differ in the number of copies of segments of their genomes. Certain aspects of copy number variation have traditionally been difficult to study using short-read sequencing data. For example, standard analyses often cannot tell whether the duplicated copies of a segment are located near the original copy or are dispersed to other regions of the genome. Another aspect of copy number variation that has been difficult to study is the detection of mutations in the copy number of DNA segments passed down from parents to their children, particularly when the mutations affect genome segments which already display common copy number variation in the population. We develop an analytical approach to solving these problems when sequencing data is available for all members of families with at least two children. This method is based on determining the number of parental haplotypes the two siblings share at each location in their genome, and using that information to determine the possible inheritance patterns that might explain the copy numbers we observe in each family member. We show that dispersed duplications and mutations can be identified by looking for copy number variants that do not follow these expected inheritance patterns. We use this approach to determine the location of 95 common duplications which are dispersed to distant regions of the genome, and demonstrate that these duplications are linked to genetic variants that affect disease risk or gene expression levels. We also identify a set of copy number mutations not detected by previous analyses of sequencing data from a large cohort of families, and show that repetitive and complex regions of the genome undergo frequent mutations in copy number.

32 A Survey of Copy Number Variation in the Porcine Genome Detected from Whole-Genome Sequence.

2018 ◽  
Vol 96 (suppl_2) ◽  
pp. 17-18
Author(s):  
B N Keel ◽  
D J Nonneman ◽  
G A Rohrer
Keyword(s):  
Copy Number Variation ◽  
Genome Sequence ◽  
Copy Number ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Porcine Genome ◽  
Number Variation

P1-053: OLFACTORY RECEPTOR COPY NUMBER VARIATION INVOLVED IN ALZHEIMER'S DISEASE

2014 ◽  
Vol 10 ◽  
pp. P322-P323
Author(s):  
Caroline Van Cauwenberghe ◽  
Karolien Bettens ◽  
Sebastiaan Engelborghs ◽  
Mathieu Vandenbulcke ◽  
Rik R. Vandenberghe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Copy Number Variation ◽  
Olfactory Receptor ◽  
Copy Number ◽  
Number Variation

scholarly journals Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project

Genomics ◽  
2019 ◽  
Vol 111 (4) ◽  
pp. 808-818 ◽  
Author(s):  
Adam C. Naj ◽  
Honghuang Lin ◽  
Badri N. Vardarajan ◽  
Simon White ◽  
Daniel Lancour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quality Control ◽  
Genome Sequence ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Genome Sequence Data ◽  
Sequencing Project

scholarly journals Genome-Wide Scan for Copy Number Variation Association with Age at Onset of Alzheimer's Disease

2012 ◽  
Vol 33 (2) ◽  
pp. 517-523 ◽  
Author(s):  
Kinga Szigeti ◽  
Deepika Lal ◽  
Yanchun Li ◽  
Rachelle S. Doody ◽  
Kirk Wilhelmsen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Copy Number Variation ◽  
Copy Number ◽  
Age At Onset ◽  
Genome Wide ◽  
Number Variation ◽  
Genome Wide Scan
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