A genome-wide survey of copy number variations reveals an asymmetric evolution of duplicated genes in rice

Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-nucleotide polymorphisms in several genomic regions have been found to be associated with AF. However, these loci do not contribute to all the genetic risks of AF or AF related thromboembolic risks, suggesting that there are other genetic factors or variants not yet discovered. In the human genome, copy number variations (CNVs) could also contribute to disease susceptibility. In the present study, we sought to identify CNVs determining the AF-related thromboembolic risk. Using a genome-wide approach in 109 patients with AF and thromboembolic stroke and 14,666 controls from the Taiwanese general population (Taiwan Biobank), we first identified deletions in chromosomal regions 1p36.32-1p36.33, 5p15.33, 8q24.3 and 19p13.3 and amplifications in 14q11.2 that were significantly associated with AF-related stroke in the Taiwanese population. In these regions, 148 genes were involved, including several microRNAs and long non-recoding RNAs. Using a pathway analysis, we found deletions in GNB1, PRKCZ, and GNG7 genes related to the alpha-adrenergic receptor signaling pathway that play a major role in determining the risk of an AF-related stroke. In conclusion, CNVs may be genetic predictors of a risk of a thromboembolic stroke for patients with AF, possibly pointing to an impaired alpha-adrenergic signaling pathway in the mechanism of AF-related thromboembolism.

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A genome-wide association study of copy number variations with umbilical hernia in swine

Animal Genetics ◽

10.1111/age.12402 ◽

2016 ◽

Vol 47 (3) ◽

pp. 298-305 ◽

Cited By ~ 14

Author(s):

Yi Long ◽

Ying Su ◽

Huashui Ai ◽

Zhiyan Zhang ◽

Bin Yang ◽

...

Keyword(s):

Association Study ◽

Copy Number ◽

Umbilical Hernia ◽

Genome Wide Association Study ◽

Copy Number Variations ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome

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Comparative analyses of copy number variations between Bos taurus and Bos indicus

BMC Genomics ◽

10.1186/s12864-020-07097-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Yan Hu ◽

Han Xia ◽

Mingxun Li ◽

Chang Xu ◽

Xiaowei Ye ◽

...

Keyword(s):

Copy Number ◽

Muscle Development ◽

Reference Genome ◽

Bos Taurus ◽

Bos Indicus ◽

Copy Number Variations ◽

Genome Wide ◽

A Genome ◽

Detection Strategies ◽

Specific Sequences

Abstract Background Bos taurus and Bos indicus are two main sub-species of cattle. However, the differential copy number variations (CNVs) between them are not yet well studied. Results Based on the new high-quality cattle reference genome ARS-UCD1.2, we identified 13,234 non-redundant CNV regions (CNVRs) from 73 animals of 10 cattle breeds (4 Bos taurus and 6 Bos indicus), by integrating three detection strategies. While 6990 CNVRs (52.82%) were shared by Bos taurus and Bos indicus, large CNV differences were discovered between them and these differences could be used to successfully separate animals into two subspecies. We found that 2212 and 538 genes uniquely overlapped with either indicine-specific CNVRs and or taurine-specific CNVRs, respectively. Based on FST, we detected 16 candidate lineage-differential CNV segments (top 0.1%) under selection, which overlapped with eight genes (CTNNA1, ENSBTAG00000004415, PKN2, BMPER, PDE1C, DNAJC18, MUSK, and PLCXD3). Moreover, we obtained 1.74 Mbp indicine-specific sequences, which could only be mapped on the Bos indicus reference genome UOA_Brahman_1. We found these sequences and their associated genes were related to heat resistance, lipid and ATP metabolic process, and muscle development under selection. We further analyzed and validated the top significant lineage-differential CNV. This CNV overlapped genes related to muscle cell differentiation, which might be generated from a retropseudogene of CTH but was deleted along Bos indicus lineage. Conclusions This study presents a genome wide CNV comparison between Bos taurus and Bos indicus. It supplied essential genome diversity information for understanding of adaptation and phenotype differences between the Bos taurus and Bos indicus populations.

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Genome-wide copy number variations in a large cohort of bantu African children

BMC Medical Genomics ◽

10.1186/s12920-021-00978-z ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Feyza Yilmaz ◽

Megan Null ◽

David Astling ◽

Hung-Chun Yu ◽

Joanne Cole ◽

...

Keyword(s):

Copy Number ◽

Developmental Disorders ◽

African Ancestry ◽

22Q11.2 Deletion Syndrome ◽

Copy Number Variations ◽

Genomic Variation ◽

Deletion Syndrome ◽

Genome Wide ◽

A Genome ◽

Genomic Regions

Abstract Background Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. Methods We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. Results We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. Conclusions These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.

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Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study

Frontiers in Physiology ◽

10.3389/fphys.2021.637306 ◽

2021 ◽

Vol 12 ◽

Author(s):

Norliana Ghazali ◽

Normastura Abd Rahman ◽

Azlina Ahmad ◽

Sarina Sulong ◽

Thirumulu Ponnuraj Kannan

Keyword(s):

Copy Number Variation ◽

Cleft Palate ◽

Copy Number ◽

Cleft Lip ◽

Genome Wide Association Study ◽

Quantitative Polymerase Chain Reaction ◽

Copy Number Variations ◽

Genome Wide ◽

A Genome ◽

Number Variation

Nonsyndromic cleft lip and or without cleft palate (NSCL/P) with the hypodontia is a common developmental abnormality in humans and animals. This study identified the genetic aberration involved in both NSCL/P and hypodontia pathogenesis. A cross-sectional study using genome-wide study copy number variation-targeted CytoScan 750K array carried out on salivary samples from 61 NSCL/P and 20 noncleft with and without hypodontia Malay subjects aged 7–13 years old. Copy number variations (CNVs) of SKI and fragile histidine triad (FHIT) were identified in NSCL/P and noncleft children using quantitative polymerase chain reaction (qPCR) as a validation analysis. Copy number calculated (CNC) for each gene determined with Applied Biosystems CopyCaller Software v2.0. The six significant CNVs included gains (12q14.3, 15q26.3, 1p36.32, and 1p36.33) and losses (3p14.2 and 4q13.2) in NSCL/P with hypodontia patients compared with the NSCL/P only. The genes located in these regions encoded LEMD3, IGF1R, TP73, SKI, FHIT, and UGT2β15. There were a significant gain and loss of both SKI and FHIT copy number in NSCL/P with hypodontia compared with the noncleft group (p < 0.05). The results supported that CNVs significantly furnish to the development of NSCL/P with hypodontia.

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A Genome Wide Copy Number Variations Analysis in Autism Spectrum Disorder (Asd) and Intellectual Disability (Id) in Italian Families

Journal of Genetic Syndromes & Gene Therapy ◽

10.4172/2157-7412.1000307 ◽

2016 ◽

Vol 7 (5) ◽

Cited By ~ 1

Author(s):

Mucciolo Mafalda ◽

Chiara Di Marco ◽

Roberto Canitano ◽

Sabrina Buoni ◽

Elisa Frullanti ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Intellectual Disability ◽

Copy Number ◽

Autism Spectrum ◽

Copy Number Variations ◽

Spectrum Disorder ◽

Genome Wide ◽

A Genome

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Mapping of genome-wide copy number variations in the Iranian indigenous cattle using a dense SNP data set

Animal Production Science ◽

10.1071/an16384 ◽

2018 ◽

Vol 58 (7) ◽

pp. 1192 ◽

Cited By ~ 3

Author(s):

K. Karimi ◽

A. Esmailizadeh ◽

D. D. Wu ◽

C. Gondro

Keyword(s):

Copy Number ◽

Copy Number Variations ◽

Indigenous Cattle ◽

Data Set ◽

Single Nucleotide ◽

Snp Data ◽

Genome Wide ◽

A Genome ◽

Wide Range ◽

Environmental Responses

The objective of this study was to present the first map of the copy number variations (CNVs) in Iranian indigenous cattle based on a high-density single nucleotide polymorphism (SNP) dataset. A total of 90 individuals were genotyped using the Illumina BovineHD BeadChip containing 777 962 SNPs. The QuantiSNP algorithm was used to perform a genome-wide CNV detection across autosomal genome. After merging the overlapping CNV, a total of 221 CNV regions were identified encompassing 36.4 Mb or 1.44% of the bovine autosomal genome. The length of the CNV regions ranged from 3.5 to 2252.8 Kb with an average of 163.8 Kb. These regions included 147 loss (66.52%) and 74 gain (33.48%) events containing a total of 637 annotated Ensembl genes. Gene ontology analysis revealed that most of genes in the CNV regions were involved in environmental responses, disease susceptibility and immune system functions. Furthermore, 543 of these genes corresponded to the human orthologous genes, which involved in a wide range of biological functions. Altogether, 73% of the 221 CNV regions overlapped either completely or partially with those previously reported in other cattle studies. Moreover, novel CNV regions involved several quantitative trait loci (QTL)-related to adaptative traits of Iranian indigenous cattle. These results provided a basis to conduct future studies on association between CNV regions and phenotypic variations in the Iranian indigenous cattle.

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