scholarly journals PSVII-37 Late-Breaking Abstract: CNV analysis of indigenous sheep reveals genes linked to disease resistance and adaptation

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 339-339
Author(s):  
Annelin Molotsi
Keyword(s):  
Candidate Genes ◽  
Copy Number ◽  
Structural Changes ◽  
Gene Annotation ◽  
Smallholder Farmers ◽  
Copy Number Variations ◽  
Ovis Aries ◽  
Matrix Composition ◽  
Low Input ◽  
Gene Group

Abstract Smallholder farmers often make use of low-input systems, suggesting that robust and adaptable individuals are needed in these systems that have good production and reproduction in these low-input systems. One of the reasons certain individuals may be more adaptable or have higher production outputs could be due to the presence of advantageous mutations or genetic structural variants. Genetic variants, namely copy number variations (CNVs), are structural changes to the DNA and are larger than a single nucleotide. In this study, 47 sheep were investigated for the presence of CNVs. A total of 206 CNVs passed quality control. These CNVs were compared to the NCBI RefSeq Ovis aries: Oar_v4.0 to identify candidate genes located within or overlapping the copy number variations identified. Gene annotation analysis was carried out on the identified candidate genes. Gene annotation assigned the candidate genes to two gene groups. The first gene group were protein coding genes responsible for interferons that are the natural defences individuals have against viral and bacterial infection. The second gene group was found to be responsible for a variety of biological functions including transport, metabolic precursors, neurogenesis, signalling as well as bone and cartilage matrix composition along with a number of other important functions. This indicates that CNVs could have various effects on important biological process which could possibly influence an individual’s survival or even production and reproduction. This highlights the need for CNV studies to determine the influence of these CNVs and how they can be utilised in breeding programmes to improve adaptation and production outputs.

scholarly journals Copy Number Variation of Immune-Related Genes and Their Association with Iodine in Adults with Autoimmune Thyroid Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Xing Jin ◽  
Yunfeng Guan ◽  
Hongmei Shen ◽  
Yi Pang ◽  
Lixiang Liu ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Copy Number ◽  
Urinary Iodine ◽  
Copy Number Variations ◽  
Thyroid Diseases ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Iodine Level ◽  
Environmental Trigger ◽  
Immune Related Genes

Background. Autoimmune thyroid diseases (AITD) are complex conditions that are caused by an interaction between genetic susceptibility and environmental triggers. Iodine is already known to be an environmental trigger for AITD, but genes associated with susceptibility need to be further assessed. Therefore, the aims of this study were to assess the association between copy number variations (CNVs) and AITD, to identify genes related with susceptibility to AITD, and to investigate the interaction between iodine status and CNVs in the occurrence of AITD. Methods. Blood samples from 15 patients with AITD and 15 controls were assessed by chromosome microarray to identify candidate genes. The copy number of candidate genes and urinary iodine level was determined in adults from areas of different iodine statuses including 158 patients and 181 controls. Results. The immune-related genes, SIRPB1 and TMEM91, were selected as candidate genes. The distribution of SIRPB1 CNV in AITD patients and controls was significantly different and was considered a risk factor for AITD. There was no significant association between urinary iodine level and candidate gene CNVs. Conclusion. SIRPB1 CNV and an excess of iodine were risk factors for AITD, but an association with the occurrence of AITD was not found.

scholarly journals Copy Number Variations in Candidate Genes in Neovascular Age-Related Macular Degeneration

2011 ◽  
Vol 52 (6) ◽  
pp. 3129 ◽  
Author(s):  
Melissa M. Liu ◽  
Elvira Agrón ◽  
Emily Chew ◽  
Catherine Meyerle ◽  
Frederick L. Ferris ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Candidate Genes ◽  
Copy Number ◽  
Copy Number Variations ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals From rare Copy Number Variations to biological processes in ADHD

2019 ◽  
Author(s):  
Benjamin Harich ◽  
Monique van der Voet ◽  
Marieke Klein ◽  
Pavel Čížek ◽  
Michaela Fenckova ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Protein Interactions ◽  
Genetic Variants ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Copy Number Variations ◽  
Model Organisms ◽  
Common Genetic Variants ◽  
Number Variation

AbstractAimAttention-deficit/hyperactivity disorder (ADHD) is a highly heritable psychiatric disorder. The objective of this study was to define ADHD-associated candidate genes, and their associated molecular modules and biological themes, based on the analysis of rare genetic variants.MethodsWe combined data from 11 published copy number variation (CNV) studies in 6176 individuals with ADHD and 25026 controls and prioritized genes by applying an integrative strategy based on criteria including recurrence in ADHD individuals, absence in controls, complete coverage in copy number gains, and presence in the minimal region common to overlapping CNVs, as well as on protein-protein interactions and information from cross-species genotype-phenotype annotation.ResultsWe localized 2241 eligible genes in the 1532 reported CNVs, of which we classified 432 as high-priority ADHD candidate genes. The high-priority ADHD candidate genes were significantly co-expressed in the brain. A network of 66 genes was supported by ADHD-relevant phenotypes in the cross-species database. In addition, four significantly interconnected protein modules were found among the high-priority ADHD genes. A total of 26 genes were observed across all applied bioinformatic methods. Look-up in the latest genome-wide association study for ADHD showed that among those 26, POLR3C and RBFOX1 were also supported by common genetic variants.ConclusionsIntegration of a stringent filtering procedure in CNV studies with suitable bioinformatics approaches can identify ADHD candidate genes at increased levels of credibility. Our pipeline provides additional insight in the molecular mechanisms underlying ADHD and allows prioritization of genes for functional validation in validated model organisms.

scholarly journals Functional and population genetic features of copy number variations in two dairy cattle populations

2020 ◽  
Author(s):  
Young-Lim Lee ◽  
Mirte Bosse ◽  
Erik Mullaart ◽  
Martien A. M. Groenen ◽  
Roel F. Veerkamp ◽  
...  
Keyword(s):  
Population Genetics ◽  
Linkage Disequilibrium ◽  
Dairy Cattle ◽  
Candidate Genes ◽  
Population Differentiation ◽  
Copy Number ◽  
Copy Number Variations ◽  
Functional Impact ◽  
Wide Range ◽  
Differentiation Index

Abstract Background Copy Number Variations (CNVs) are gain or loss of DNA segments that are known to play a role in shaping a wide range of phenotypes. In this study, we used two dairy cattle populations, Holstein Friesian and Jersey, to discover CNVs using the Illumina BovineHD Genotyping BeadChip aligned to the ARS-UCD1.2 assembly. The discovered CNVs were investigated for their functional impact and their population genetics features. Results We discovered 14,272 autosomal CNVs, which were aggregated into 1,755 CNV regions (CNVR) from 451 animals. These CNVRs together cover 2.8% of the bovine autosomes. The assessment of the functional impact of CNVRs showed that rare CNVRs (MAF < 0.01) are more likely to overlap with genes, than common CNVRs (MAF ≥ 0.05). The Population differentiation index (Fst) based on CNVRs revealed multiple highly diverged CNVRs between the two breeds. Some of these CNVRs overlapped with candidate genes such as MGAM and ADAMTS17 genes , which are related to starch digestion and body size, respectively. Lastly, linkage disequilibrium (LD) between CNVRs and BovineHD BeadChip SNPs was generally low, close to 0, although common deletions (MAF ≥ 0.05) showed slightly higher LD ( r 2 =~0.1 at 10kb distance) than the rest. Nevertheless, this LD is still lower than SNP-SNP LD ( r 2 =~0.5 at 10kb distance). Conclusions Our analyses showed that CNVRs detected using BovineHD BeadChip arrays are likely to be functional. This finding indicates that CNVs can potentially disrupt the function of genes and thus might alter phenotypes. Also, the population differentiation index revealed two candidate genes, MGAM and ADAMTS17 , which hint at adaptive evolution between the two populations. Lastly, low CNVR-SNP LD implies that genetic variation from CNVs might not be fully captured in routine animal genetic evaluation, which relies solely on SNP markers. Keywords : Copy number variations, Bos taurus , Linkage disequilibrium, population genetics

scholarly journals Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways

2012 ◽  
Vol 21 (15) ◽  
pp. 3513-3523 ◽  
Author(s):  
Anthony J. Griswold ◽  
Deqiong Ma ◽  
Holly N. Cukier ◽  
Laura D. Nations ◽  
Mike A. Schmidt ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Candidate Genes ◽  
Copy Number ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Spectrum Disorder

scholarly journals Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 141
Author(s):  
Yan-Ran Sheng ◽  
Shun-Yu Hou ◽  
Wen-Ting Hu ◽  
Chun-Yan Wei ◽  
Yu-Kai Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Candidate Genes ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Single Nucleotide Polymorphism Array ◽  
Age Groups ◽  
Snp Array ◽  
Copy Number Variations ◽  
Functional Enrichment

It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.

scholarly journals Isolated GH deficiency: mutation screening and copy number analysis of HMGA2 and CDK6 genes

2011 ◽  
Vol 165 (4) ◽  
pp. 537-544 ◽  
Author(s):  
Darya Gorbenko Del Blanco ◽  
Laura C G de Graaff ◽  
Dirk Posthouwer ◽  
Theo J Visser ◽  
Anita C S Hokken-Koelega
Keyword(s):  
Candidate Genes ◽  
Copy Number ◽  
Gh Deficiency ◽  
Association Studies ◽  
Normal Population ◽  
Mutation Screening ◽  
Copy Number Variations ◽  
Published Data ◽  
Growth Disorders ◽  
Genome Wide Association Studies

ObjectiveIn most patients, the genetic cause of isolated GH deficiency (IGHD) is unknown. By identifying several genes associated with height variability within the normal population, three separate genome-wide association studies provided new candidate genes for human growth disorders. We selected two of them for genetic screening of our IGHD population.AimWe aimed to determine whether high-mobility group A2 (HMGA2) and cyclin-dependent protein kinase 6 (CDK6) are involved in the pathogenicity of IGHD.MethodsWe directly sequenced coding regions and exon–intron boundaries of the genesHMGA2andCDK6in 105 Caucasian IGHD patients from the Dutch HYPOPIT study. In addition, we developed a new probe set of multiplex ligation-dependent probe amplification for both genes in order to detect copy number variations.ResultsIn one patient with classical IGHD phenotype, we identified a new heterozygous 20 bp deletion in the intronic region ofHMGA2(c.250-29_-9del), which was absent in the databases and healthy controls. Together, with recently published data concerning the 12q14 microdeletion syndrome, where patients with anHMGA2haploinsufficiency had proportionate short stature, this study provides further support of the important role for HMGA2 in growth. InCDK6, we found only known polymorphisms.ConclusionsThis study provides the first report of a deletion in theHMGA2gene that might be related to IGHD. We suggest that this gene is investigated as a second screening in patients with a classical IGHD phenotype in which mutations in classical candidate genes have been excluded.

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