scholarly journals Comparative Enhancer Map of Cattle Muscle Genome Annotated by ATAC-Seq

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiukai Cao ◽  
Jie Cheng ◽  
Yongzhen Huang ◽  
Xianyong Lan ◽  
Chuzhao Lei ◽  
...  
Keyword(s):  
Muscle Development ◽  
Genome Wide Association Study ◽  
Average Daily Gain ◽  
Regulatory Elements ◽  
Luciferase Reporter ◽  
Gene Promoters ◽  
Functional Elements ◽  
Enhancer Activity ◽  
Genome Wide ◽  
Mouse Embryo Development

Annotating regulatory elements could benefit the interpretation of the molecular mechanism of genome-wide association study (GWAS) hits. In this work, we performed transposase-accessible chromatin with sequencing (ATAC-seq) to annotate the cattle muscle genome's functional elements. A total of 10,023 and 11,360 peaks were revealed in muscle genomes of adult and embryo cattle, respectively. The two peak sets produced 8,850 differentially accessible regions (DARs), including 2,515 promoters and 4,319 putative enhancers. These functional elements were associated with the cell cycle, muscle development, and lipid metabolism. A total of 15 putative enhancers were selected for a dual-luciferase reporter assay, and 12 of them showed enhancer activity in cattle myoblasts. Interestingly, the GeneHancer database has annotated the interactions of eight active enhancers with gene promoters, such as embryo-specific peak1053 (log2FC = 1.81, embryo/adult, E/A) with ligand-dependent nuclear receptor corepressor-like protein (LCORL) and embryo-specific peak4218 (log2FC = 1.81) with FERM domain-containing 8 (FRMD8). A total of 295 GWAS loci from the animal QTL database were mapped to 183 putative enhancers, including rs109554838 (associated with cattle body weight and average daily gain) to peak1053 and rs110294629 (associated with beef shear force and tenderness score) to peak4218. Notably, peak4218 has been found to be involved in mouse embryo development. Deleting peak4218 clearly reduced luciferase activity (P = 3.30E-04). Our comparative enhancer map is expected to benefit the area of beef cattle breeding.

Periodontitis Risk Variants at SIGLEC5 Impair ERG and MAFB Binding

2021 ◽  
pp. 002203452110499
Author(s):  
R. Mueller ◽  
A. Chopra ◽  
H. Dommisch ◽  
A.S. Schaefer
Keyword(s):  
Association Study ◽  
Target Gene ◽  
Genome Wide Association Study ◽  
Biological Effects ◽  
Regulatory Elements ◽  
Genome Wide Association ◽  
Luciferase Reporter ◽  
Genome Wide ◽  
A Genome ◽  
Allele Specific

Periodontitis is a common complex inflammatory disease of the oral cavity. It is characterized by inflammation of gingival tissues and alveolar bone loss. Recently, a genome-wide association study and 2 genome-wide association study meta-analyses found 2 associated regions (haplotype blocks) at the inhibitory immune receptor gene SIGLEC5 to increase the risk for periodontitis. The aims of the current study were the identification of the putative causal variants underlying these associations, characterization of their molecular biological effects, and validation of SIGLEC5 as the target gene. We mapped the associated single-nucleotide polymorphisms to DNA elements with predictive features of regulatory functions and screened the associated alleles for transcription factor (TF) binding sites. Antibody electrophoretic mobility shift assays (EMSAs) with allele-specific probes were used to identify TF binding and to quantify allele-specific effects on binding affinities. Luciferase reporter assays were used to quantify the effect directions and allele-specific strength of the associated regulatory elements. We used CRISPR-dCas9 gene activation to validate SIGLEC5 as a target of the association. EMSA in peripheral blood mononuclear cells showed that E-26 transformation–specific TF-related gene (ERG) binds at rs11084095, with almost complete loss of binding at the minor A-allele. Allele-specific reporter genes showed enhancer function of the DNA sequence at rs11084095, which was abrogated in the background of the A-allele. EMSA in B lymphocytes showed that TF MAF bZIP (MAFB) binds at the common G-allele of rs4284742, whereas the minor A-allele reduced TF binding by 69%, corresponding to 9-fold reduction of luciferase reporter gene activity by the A-allele. Using CRISPR-dCas9, we showed that the enhancer at rs4284742 strongly activated SIGLEC5 expression, validating this gene as the target gene of the association. We conclude that rs11084095 and rs4284742 are putatively causal for the genome-wide significant associations with periodontitis at SIGLEC5 that impair ERG and MAFB binding, respectively.

scholarly journals Weighted Single-Step Genome-Wide Association Study for Growth Traits in Chinese Simmental Beef Cattle

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 189 ◽  
Author(s):  
Zhanwei Zhuang ◽  
Lingyang Xu ◽  
Jie Yang ◽  
Huijiang Gao ◽  
Lupei Zhang ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Association Study ◽  
Muscle Development ◽  
Genome Wide Association Study ◽  
Growth Traits ◽  
Average Daily Gain ◽  
Single Step ◽  
Genome Wide Association ◽  
Meat Production ◽  
Genome Wide

Improving the genetic process of growth traits is one of the major goals in the beef cattle industry, as it can increase meat production and reduce the cost of raising animals. Although several quantitative trait loci affecting growth traits in beef cattle have been identified, the genetic architecture of these economically important traits remains elusive. This study aims to map single nucleotide polymorphisms (SNPs) and genes associated with birth weight (BW), yearling weight (YW), average daily gain from birth to yearling (BYADG), and body weight at the age of 18 months (18MW) in a Chinese Simmental beef cattle population using a weighted, single-step, genome-wide association study (wssGWAS). Phenotypic and pedigree data from 6022 animals and genotypes from 744 animals (596,297 SNPs) were used for an association analysis. The results showed that 66 genomic windows explained 1.01–20.15% of the genetic variance for the four examined traits, together with the genes near the top SNP within each window. Furthermore, the identified genomic windows (>1%) explained 50.56%, 57.71%, 61.78%, and 37.82% of the genetic variances for BW, YW, BYADG, and 18MW, respectively. Genes with potential functions in muscle development and regulation of cell growth were highlighted as candidates for growth traits in Simmental cattle (SQOR and TBCB for BW, MYH10 for YW, RLF for BYADG, and ARHGAP31 for 18MW). Moreover, we found 40 SNPs that had not previously been identified as being associated with growth traits in cattle. These findings will further advance our understanding of the genetic basis for growth traits and will be useful for the molecular breeding of BW, YW, BYADG, and 18MW in the context of genomic selection in beef cattle.

scholarly journals Genome-Wide Identification and Analysis of the APETALA2 (AP2) Transcription Factor in Dendrobium officinale

2021 ◽  
Vol 22 (10) ◽  
pp. 5221
Author(s):  
Danqi Zeng ◽  
Jaime A. Teixeira da Silva ◽  
Mingze Zhang ◽  
Zhenming Yu ◽  
Can Si ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Flower Development ◽  
Regulatory Elements ◽  
Negative Control ◽  
Dendrobium Officinale ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Luciferase Reporter Gene ◽  
Genome Wide ◽  
Ap2 Transcription Factor

The APETALA2 (AP2) transcription factors (TFs) play crucial roles in regulating development in plants. However, a comprehensive analysis of the AP2 family members in a valuable Chinese herbal orchid, Dendrobium officinale, or in other orchids, is limited. In this study, the 14 DoAP2 TFs that were identified from the D. officinale genome and named DoAP2-1 to DoAP2-14 were divided into three clades: euAP2, euANT, and basalANT. The promoters of all DoAP2 genes contained cis-regulatory elements related to plant development and also responsive to plant hormones and stress. qRT-PCR analysis showed the abundant expression of DoAP2-2, DoAP2-5, DoAP2-7, DoAP2-8 and DoAP2-12 genes in protocorm-like bodies (PLBs), while DoAP2-3, DoAP2-4, DoAP2-6, DoAP2-9, DoAP2-10 and DoAP2-11 expression was strong in plantlets. In addition, the expression of some DoAP2 genes was down-regulated during flower development. These results suggest that DoAP2 genes may play roles in plant regeneration and flower development in D. officinale. Four DoAP2 genes (DoAP2-1 from euAP2, DoAP2-2 from euANT, and DoAP2-6 and DoAP2-11 from basal ANT) were selected for further analyses. The transcriptional activation of DoAP2-1, DoAP2-2, DoAP2-6 and DoAP2-11 proteins, which were localized in the nucleus of Arabidopsis thaliana mesophyll protoplasts, was further analyzed by a dual-luciferase reporter gene system in Nicotiana benthamiana leaves. Our data showed that pBD-DoAP2-1, pBD-DoAP2-2, pBD-DoAP2-6 and pBD-DoAP2-11 significantly repressed the expression of the LUC reporter compared with the negative control (pBD), suggesting that these DoAP2 proteins may act as transcriptional repressors in the nucleus of plant cells. Our findings on AP2 genes in D. officinale shed light on the function of AP2 genes in this orchid and other plant species.

scholarly journals Genome-wide association for heifer reproduction and calf performance traits in beef cattle

Genome ◽  
2015 ◽  
Vol 58 (12) ◽  
pp. 549-557 ◽  
Author(s):  
Everestus C. Akanno ◽  
Graham Plastow ◽  
Carolyn Fitzsimmons ◽  
Stephen P. Miller ◽  
Vern Baron ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Genome Wide Association Study ◽  
Average Daily Gain ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Research Centre ◽  
Genome Wide ◽  
A Genome ◽  
Starting Point ◽  
And Performance

The aim of this study was to identify SNP markers that associate with variation in beef heifer reproduction and performance of their calves. A genome-wide association study was performed by means of the generalized quasi-likelihood score (GQLS) method using heifer genotypes from the BovineSNP50 BeadChip and estimated breeding values for pre-breeding body weight (PBW), pregnancy rate (PR), calving difficulty (CD), age at first calving (AFC), calf birth weight (BWT), calf weaning weight (WWT), and calf pre-weaning average daily gain (ADG). Data consisted of 785 replacement heifers from three Canadian research herds, namely Brandon Research Centre, Brandon, Manitoba, University of Alberta Roy Berg Kinsella Ranch, Kinsella, Alberta, and Lacombe Research Centre, Lacombe, Alberta. After applying a false discovery rate correction at a 5% significance level, a total of 4, 3, 3, 9, 6, 2, and 1 SNPs were significantly associated with PBW, PR, CD, AFC, BWT, WWT, and ADG, respectively. These SNPs were located on chromosomes 1, 5–7, 9, 13–16, 19–21, 24, 25, and 27–29. Chromosomes 1, 5, and 24 had SNPs with pleiotropic effects. New significant SNPs that impact functional traits were detected, many of which have not been previously reported. The results of this study support quantitative genetic studies related to the inheritance of these traits, and provides new knowledge regarding beef cattle quantitative trait loci effects. The identification of these SNPs provides a starting point to identify genes affecting heifer reproduction traits and performance of their calves (BWT, WWT, and ADG). They also contribute to a better understanding of the biology underlying these traits and will be potentially useful in marker- and genome-assisted selection and management.

A novel regulatory element between the human FGA and FGG genes

2012 ◽  
Vol 108 (09) ◽  
pp. 427-434 ◽  
Author(s):  
Richard J. Fish ◽  
Marguerite Neerman-Arbez
Keyword(s):  
Gene Cluster ◽  
Fluorescent Protein ◽  
Regulatory Element ◽  
Luciferase Reporter ◽  
Transgenic Zebrafish ◽  
Regulatory Sequences ◽  
Gene Promoters ◽  
Cvd Risk ◽  
Enhancer Activity

SummaryHigh circulating fibrinogen levels correlate with cardiovascular disease (CVD) risk. Fibrinogen levels vary between people and also change in response to physiological and environmental stimuli. A modest proportion of the variation in fibrinogen levels can be explained by genotype, inferring that variation in genomic sequences that regulate the fibri-nogen genes (FGA, FGB and FGG) may affect hepatic fibrinogen production and perhaps CVD risk. We previously identified a conserved liver enhancer in the fibrinogen gene cluster (CNC12), between FGB and FGA. Genome-wide Chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated that transcription factors which bind fibrinogen gene promoters also interact with CNC12, as well as two potential fibrinogen enhancers (PFE), between FGA and FGG. Here we show that one of the PFE sequences has potent hepatocyte enhancer activity. Using a luciferase reporter gene system, we found that PFE2 enhances minimal promoter- and FGA promoter-driven gene expression in hepatoma cells, regardless of its orientation with respect to the promoters. A region within PFE2 bears a short series of conserved nucleotides which maintain enhancer activity without flanking sequence. We also demonstrate that PFE2 is a liver enhancer in vivo, driving enhanced green fluorescent protein expression in transgenic zebrafish larval livers. Our study shows that combining public domain ChIP-seq data with in vitro and in vivo functional tests can identify novel fibrinogen gene cluster regulatory sequences. Variation in such elements could affect fibrinogen production and influence CVD risk.

scholarly journals Comprehensive Genomic Discovery of Non-Coding Transcriptional Enhancers in the African Malaria Vector Anopheles coluzzii

2022 ◽  
Vol 12 ◽  
Author(s):  
Inge Holm ◽  
Luisa Nardini ◽  
Adrien Pain ◽  
Emmanuel Bischoff ◽  
Cameron E. Anderson ◽  
...  
Keyword(s):  
Malaria Vector ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Insect Vector ◽  
Anopheles Coluzzii ◽  
Gene Promoters ◽  
Transcriptional Enhancers ◽  
Genome Wide ◽  
A Genome

Almost all regulation of gene expression in eukaryotic genomes is mediated by the action of distant non-coding transcriptional enhancers upon proximal gene promoters. Enhancer locations cannot be accurately predicted bioinformatically because of the absence of a defined sequence code, and thus functional assays are required for their direct detection. Here we used a massively parallel reporter assay, Self-Transcribing Active Regulatory Region sequencing (STARR-seq), to generate the first comprehensive genome-wide map of enhancers in Anopheles coluzzii, a major African malaria vector in the Gambiae species complex. The screen was carried out by transfecting reporter libraries created from the genomic DNA of 60 wild A. coluzzii from Burkina Faso into A. coluzzii 4a3A cells, in order to functionally query enhancer activity of the natural population within the homologous cellular context. We report a catalog of 3,288 active genomic enhancers that were significant across three biological replicates, 74% of them located in intergenic and intronic regions. The STARR-seq enhancer screen is chromatin-free and thus detects inherent activity of a comprehensive catalog of enhancers that may be restricted in vivo to specific cell types or developmental stages. Testing of a validation panel of enhancer candidates using manual luciferase assays confirmed enhancer function in 26 of 28 (93%) of the candidates over a wide dynamic range of activity from two to at least 16-fold activity above baseline. The enhancers occupy only 0.7% of the genome, and display distinct composition features. The enhancer compartment is significantly enriched for 15 transcription factor binding site signatures, and displays divergence for specific dinucleotide repeats, as compared to matched non-enhancer genomic controls. The genome-wide catalog of A. coluzzii enhancers is publicly available in a simple searchable graphic format. This enhancer catalogue will be valuable in linking genetic and phenotypic variation, in identifying regulatory elements that could be employed in vector manipulation, and in better targeting of chromosome editing to minimize extraneous regulation influences on the introduced sequences.Importance: Understanding the role of the non-coding regulatory genome in complex disease phenotypes is essential, but even in well-characterized model organisms, identification of regulatory regions within the vast non-coding genome remains a challenge. We used a large-scale assay to generate a genome wide map of transcriptional enhancers. Such a catalogue for the important malaria vector, Anopheles coluzzii, will be an important research tool as the role of non-coding regulatory variation in differential susceptibility to malaria infection is explored and as a public resource for research on this important insect vector of disease.

scholarly journals Genomic characterization of the adolescent idiopathic scoliosis associated transcriptome and regulome

2020 ◽  
Author(s):  
Nadja Makki ◽  
Jingjing Zhao ◽  
Zhaoyang Liu ◽  
Walter L. Eckalbar ◽  
Aki Ushiki ◽  
...  
Keyword(s):  
Adolescent Idiopathic Scoliosis ◽  
Connective Tissue ◽  
Idiopathic Scoliosis ◽  
Association Studies ◽  
Regulatory Elements ◽  
Intervertebral Discs ◽  
Genome Wide Association Studies ◽  
Specific Expression ◽  
Enhancer Activity ◽  
Genome Wide

AbstractAdolescent idiopathic scoliosis (AIS), a sideways curvature of the spine, is the most common pediatric musculoskeletal disorder, affecting ∼3% of the population worldwide. However, its genetic bases and tissues of origin remain largely unknown. Several genome-wide association studies (GWAS) have implicated nucleotide variants in noncoding sequences that control genes with important roles in cartilage, muscle, bone, connective tissue and intervertebral discs (IVDs) as drivers of AIS susceptibility. Here, we set out to define the expression of AIS-associated genes and active regulatory elements by performing RNA-seq and ChIP-seq against H3K27ac in these tissues in mouse and human. Our study highlights genetic pathways involving AIS-associated loci that regulate chondrogenesis, IVD development and connective tissue maintenance and homeostasis. In addition, we identify thousands of putative AIS-associated regulatory elements which may orchestrate tissue-specific expression in musculoskeletal tissues of the spine. Quantification of enhancer activity of several candidate regulatory elements from our study identifies three functional enhancers carrying AIS-associated GWAS SNPs at the ADGRG6 and BNC2 loci. Our findings provide a novel genome-wide catalog of AIS-relevant genes and regulatory elements and aid in the identification of novel targets for AIS causality and treatment.

Genome-wide association study for feedlot average daily gain in Nellore cattle (Bos indicus )

2014 ◽  
Vol 131 (3) ◽  
pp. 210-216 ◽  
Author(s):  
M.H.A. Santana ◽  
Y.T. Utsunomiya ◽  
H.H.R. Neves ◽  
R.C. Gomes ◽  
J.F. Garcia ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Average Daily Gain ◽  
Bos Indicus ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Nellore Cattle ◽  
Daily Gain

scholarly journals Genome-Wide Association Study of Body Weight Traits in Chinese Fine-Wool Sheep

Animals ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 170 ◽  
Author(s):  
Zengkui Lu ◽  
Yaojing Yue ◽  
Chao Yuan ◽  
Jianbin Liu ◽  
Zhiqiang Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Muscle Development ◽  
Genome Wide Association Study ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Economic Trait ◽  
Significance Levels ◽  
Genomic Regions ◽  
Selection Of

Body weight is an important economic trait for sheep and it is vital for their successful production and breeding. Therefore, identifying the genomic regions and biological pathways that contribute to understanding variability in body weight traits is significant for selection purposes. In this study, the genome-wide associations of birth, weaning, yearling, and adult weights of 460 fine-wool sheep were determined using resequencing technology. The results showed that 113 single nucleotide polymorphisms (SNPs) reached the genome-wide significance levels for the four body weight traits and 30 genes were annotated effectively, including AADACL3, VGF, NPC1, and SERPINA12. The genes annotated by these SNPs significantly enriched 78 gene ontology terms and 25 signaling pathways, and were found to mainly participate in skeletal muscle development and lipid metabolism. These genes can be used as candidate genes for body weight in sheep, and provide useful information for the production and genomic selection of Chinese fine-wool sheep.

Detection of candidate genes for growth and carcass traits using genome-wide association strategy in Chinese Simmental beef cattle

2018 ◽  
Vol 58 (2) ◽  
pp. 224 ◽  
Author(s):  
Wengang Zhang ◽  
Lingyang Xu ◽  
Huijiang Gao ◽  
Yang Wu ◽  
Xue Gao ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Candidate Genes ◽  
Genome Wide Association Study ◽  
Average Daily Gain ◽  
Carcass Traits ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Economic Traits ◽  
Cattle Industry ◽  
Genome Wide

In Chinese beef cattle industry, there are more than 60 million livestock, nearly half of which are Chinese Simmental beef cattle or Simmental crossbreds. Over the past decades, numerous quantitative trait loci for economic traits in cattle have been identified, while few studies for growth and carcass traits have been reported in Simmental beef cattle. In the present study, we conducted genome-wide association study based on BovineHD BeadChip and identified 41, 15, 3, 22 and 16 single-nucleotide polymorphisms significantly associated with average daily gain, liveweight before slaughter, carcass weight, dressing percentage and pure meat percentage respectively. In total, 18 candidate genes were found for growth and carcass traits, and four haplotype blocks for growth and carcass traits were discovered. These findings will facilitate detection of major genes and genetic variants involved in growth and carcass traits of beef cattle in further studies.

Sign in / Sign up

Export Citation Format

Share Document