DNA copy number and structural variation (CNV) contributions to adult and childhood obesity

2020 ◽  
Vol 48 (4) ◽  
pp. 1819-1828
Author(s):  
Megan Phillips ◽  
Jeganathan Ramesh Babu ◽  
Xu Wang ◽  
Thangiah Geetha
Keyword(s):  
Copy Number ◽  
Current Knowledge ◽  
Association Studies ◽  
Copy Number Variations ◽  
Genomic Diversity ◽  
Health Concern ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Comprehensive Classification ◽  
Genomic Regions

In recent years, obesity has reached epidemic proportions globally and has become a major public health concern. The development of obesity is likely caused by several behavioral, environmental, and genetic factors. Genomic variability among individuals is largely due to copy number variations (CNVs). Recent genome-wide association studies (GWAS) have successfully identified many loci containing CNV related to obesity. These obesity-related CNVs are informative to the diagnosis and treatment of genomic diseases. A more comprehensive classification of CNVs may provide the basis for determining how genomic diversity impacts the mechanisms of expression for obesity in children and adults of a variety of genders and ethnicities. In this review, we summarize current knowledge on the relationship between obesity and the CNV of several genomic regions, with an emphasis on genes at the following loci: 11q11, 1p21.1, 10q11.22, 10q26.3, 16q12.2, 16p12.3, and 4q25.

scholarly journals Dissecting Molecular Genetic Mechanisms of 1q21.1 CNV in Neuropsychiatric Disorders

2021 ◽  
Vol 22 (11) ◽  
pp. 5811
Author(s):  
Joy Yoon ◽  
Yingwei Mao
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Molecular Genetic ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Genetic Mechanisms

Pathogenic copy number variations (CNVs) contribute to the etiology of neurodevelopmental/neuropsychiatric disorders (NDs). Increased CNV burden has been found to be critically involved in NDs compared with controls in clinical studies. The 1q21.1 CNVs, rare and large chromosomal microduplications and microdeletions, are detected in many patients with NDs. Phenotypes of duplication and deletion appear at the two ends of the spectrum. Microdeletions are predominant in individuals with schizophrenia (SCZ) and microcephaly, whereas microduplications are predominant in individuals with autism spectrum disorder (ASD) and macrocephaly. However, its complexity hinders the discovery of molecular pathways and phenotypic networks. In this review, we summarize the recent genome-wide association studies (GWASs) that have identified candidate genes positively correlated with 1q21.1 CNVs, which are likely to contribute to abnormal phenotypes in carriers. We discuss the clinical data implicated in the 1q21.1 genetic structure that is strongly associated with neurodevelopmental dysfunctions like cognitive impairment and reduced synaptic plasticity. We further present variations reported in the phenotypic severity, genomic penetrance and inheritance.

scholarly journals Current analysis platforms and methods for detecting copy number variation

2013 ◽  
Vol 45 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Wenli Li ◽  
Michael Olivier
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Genomic Structural Variation ◽  
Disease Phenotypes ◽  
Human Genomes ◽  
Genome Wide ◽  
Number Variation ◽  
Genomic Regions

Copy number variation (CNV), generated through duplication or deletion events that affect one or more loci, is widespread in the human genomes and is often associated with functional consequences that may include changes in gene expression levels or fusion of genes. Genome-wide association studies indicate that some disease phenotypes and physiological pathways might be impacted by CNV in a small number of characterized genomic regions. However, the pervasiveness and full impact of such variation remains unclear. Suitable analytic methods are needed to thoroughly mine human genomes for genomic structural variation, and to explore the interplay between observed CNV and disease phenotypes, but many medical researchers are unfamiliar with the features and nuances of recently developed technologies for detecting CNV. In this article, we evaluate a suite of commonly used and recently developed approaches to uncovering genome-wide CNVs and discuss the relative merits of each.

scholarly journals Genetics in schizophrenia: where are we and what next?

2010 ◽  
Vol 12 (3) ◽  
pp. 289-303
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Molecular Genetic ◽  
Copy Number Variations ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
Genome Wide ◽  
Number Variation

Understanding the genetic basis of schizophrenia continues to be major challenge. The research done during the last two decades has provided several candidate genes which unfortunately have not been consistently replicated across or within a population. The recent genome-wide association studies (GWAS) and copy number variation (CNV) studies have provided important evidence suggesting a role of both common and rare large CNVs in schizophrenia genesis. The burden of rare copy number variations appears to be increased in schizophrenia patients. A consistent observation among the GWAS studies is the association with schizophrenia of genetic markers in the major histocompatibility complex (6p22.1)-containing genes including NOTCH4 and histone protein loci. Molecular genetic studies are also demonstrating that there is more overlap between the susceptibility genes for schizophrenia and bipolar disorder than previously suspected. In this review we summarize the major findings of the past decade and suggest areas of future research.

On the analysis of copy-number variations in genome-wide association studies: a translation of the family-based association test

2008 ◽  
Vol 32 (3) ◽  
pp. 273-284 ◽  
Author(s):  
Iuliana Ionita-Laza ◽  
George H. Perry ◽  
Benjamin A. Raby ◽  
Barbara Klanderman ◽  
Charles Lee ◽  
...  
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Copy Number Variations ◽  
Association Test ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
The Family ◽  
Family Based

PSVIII-10 Genome-wide CNV analysis unravels a deletion associated with parasite resistance in Florida native sheep

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 243-244
Author(s):  
Brittany N Diehl ◽  
Andres A Pech-Cervantes ◽  
Thomas H Terrill ◽  
Ibukun M Ogunade ◽  
Owen Rae ◽  
...  
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Chromosome 21 ◽  
Trend Test ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Parasite Resistance ◽  
Association Testing ◽  
Genome Wide ◽  
Native Sheep

Abstract Florida Native sheep is an indigenous breed from Florida and expresses superior parasite resistance. Previous candidate and genome wide association studies with Florida Native sheep have identified single nucleotide polymorphisms with additive and non-additive effects associated with parasite resistance. However, the role of other potential DNA variants, such as copy number variants (CNVs), controlling this complex trait have not been evaluated. The objective of the present study was to investigate the importance of CNVs on resistance to natural Haemonchus contortus infections in Florida Native sheep. A total of 200 sheep were evaluated in the present study. Phenotypic records included fecal egg count (FEC, eggs/gram), FAMACHA score, and packed cell volume (PCV, %). Sheep were genotyped using the GGP Ovine 50K SNP chip. The copy number analysis was used to identify CNVs using the univariate method. A total of 170 animals with CNVs and phenotypic data were used for the association testing. Association tests were carried out using single linear regression and Principal Component Analysis (PCA) correction to identify CNVs associated with FEC, FAMACHA, and PCV. To confirm our results, a second association testing using the correlation-trend test with PCA correction was performed. Significant CNVs were detected when their adjusted p-value was < 0.05 after FDR correction. A deletion CNV in chromosome 21 was associated with FEC. This DNA variant was located in intron 2 of RAB3IL gene and overlapped a QTL associated with changes in eosinophil number. Our study demonstrated for the first time that CNVs could be potentially involved with parasite resistance in this heritage sheep breed.

scholarly journals Current knowledge in hypertension genetics: mosaic theory, candidate genes and genome-wide association studies

2020 ◽  
Vol 26 (5) ◽  
pp. 490-500
Author(s):  
A. O. Konradi
Keyword(s):  
Candidate Genes ◽  
High Performance ◽  
New Technologies ◽  
Current Knowledge ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Modern Approach ◽  
Genome Wide

The article reviews monogenic forms of hypertension, data on the role of heredity of essential hypertension and candidate genes, as well as genome-wide association studies. Modern approach for the role of genetics is driven by implementation of new technologies and their productivity. High performance speed of new technologies like genome-wide association studies provide data for better knowledge of genetic markers of hypertension. The major goal nowadays for research is to reveal molecular pathways of blood pressure regulation, which can help to move from populational to individual level of understanding of pathogenesis and treatment targets.

Genome-Wide Association Studies (GWAS) for Traits Related to Fodder Quality and Biofuel in Sorghum: Progress and Prospects

2021 ◽  
Vol 28 ◽  
Author(s):  
Vinutha Kanuganahalli Somegowda ◽  
Laavanya Rayaprolu ◽  
Abhishek Rathore ◽  
Santosh Pandurang Deshpande ◽  
Rajeev Gupta
Keyword(s):  
Genetic Architecture ◽  
Association Studies ◽  
Current Status ◽  
Genome Wide Association Studies ◽  
Potential Candidate ◽  
Crop Species ◽  
Fodder Quality ◽  
Genome Wide ◽  
Genomic Regions ◽  
Model Crop

: The main focus of this review is to discuss the current status of the use of GWAS for fodder quality and biofuel owing to its similarity of traits. Sorghum is a potential multipurpose crop, popularly cultivated for various uses as food, feed fodder, and biomass for ethanol. Production of a huge quantity of biomass and genetic variation for complex sugars are the main motivation not only to use sorghum as fodder for livestock nutritionists but also a potential candidate for biofuel generation. Few studies have been reported on the knowledge transfer that can be used from the development of biofuel technologies to complement improved fodder quality and vice versa. With recent advances in genotyping technologies, GWAS became one of the primary tools used to identify the genes/genomic regions associated with the phenotype. These modern tools and technologies accelerate the genomic assisted breeding process to enhance the rate of genetic gains. Hence, this mini-review focuses on GWAS studies on genetic architecture and dissection of traits underpinning fodder quality and biofuel traits and their limited comparison with other related model crop species.

scholarly journals Genetics of COPD

2020 ◽  
Vol 82 (1) ◽  
pp. 413-431 ◽  
Author(s):  
Edwin K. Silverman
Keyword(s):  
Association Studies ◽  
Chronic Obstructive ◽  
Genome Wide Association Studies ◽  
Obstructive Pulmonary Disease ◽  
Functional Variants ◽  
Genome Wide ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Genomic Regions

Although chronic obstructive pulmonary disease (COPD) risk is strongly influenced by cigarette smoking, genetic factors are also important determinants of COPD. In addition to Mendelian syndromes such as alpha-1 antitrypsin deficiency, many genomic regions that influence COPD susceptibility have been identified in genome-wide association studies. Similarly, multiple genomic regions associated with COPD-related phenotypes, such as quantitative emphysema measures, have been found. Identifying the functional variants and key genes within these association regions remains a major challenge. However, newly identified COPD susceptibility genes are already providing novel insights into COPD pathogenesis. Network-based approaches that leverage these genetic discoveries have the potential to assist in decoding the complex genetic architecture of COPD.

scholarly journals Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update

2020 ◽  
Vol 9 (4) ◽  
pp. 1096
Author(s):  
Jessica Gambardella ◽  
Angela Lombardi ◽  
Marco Bruno Morelli ◽  
John Ferrara ◽  
Gaetano Santulli
Keyword(s):  
Human Disease ◽  
Calcium Release ◽  
Current Knowledge ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Genome Wide ◽  
Inositol 1,4,5 Trisphosphate ◽  
Human Disorders

Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.

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