31 Gametic Incompatibility: Improving the Success of Mate Allocation in Dairy Cattle

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 16-17
Author(s):  
Audrey A A Martin ◽  
Samir Id-Lahoucine ◽  
Dan Tulpan ◽  
Stephen J Leblanc ◽  
Angela Cánovas ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
System Development ◽  
Enrichment Analysis ◽  
Mendelian Inheritance ◽  
Nervous System Development ◽  
Transmission Ratio Distortion ◽  
Reproductive Capacity ◽  
Pathway Enrichment Analysis ◽  
Inbreeding Coefficients ◽  
Offspring Genotype

Abstract In the dairy industry, mate allocation is mainly based on the parents’ breeding values and inbreeding coefficients aiming to achieve the producer’s breeding goal. With artificial insemination, the portfolio of sires to choose from is large and the quality of the semen doses is standardized. However, not all sire-dam matings are equally likely to produce a successful pregnancy. Among other reproduction issues, the success of a mating could vary due to the incompatibility of gametes coming from the sire and the dam and could influence the fertilization’s success, additionally to the reproductive capacity of the parents. Considering the gametic incompatibility of the potential parents could be a novel option to improve mating plans. Under the hypothesis that gametic incompatibility has a significant effect on reproduction and reduces the odds of fertilization and pregnancy, this study aimed to determine the genetic background of gametic incompatibility. Transmission ratio distortion (TRD), which detects deviations from Mendelian inheritance expectations, is commonly used to identify deleterious mutations. We adapted the TRD model by including an interaction effect between the gametes leading to the offspring genotype to detect regions with TRD effects and gametic incompatibility. Our dataset contained 436,651 genotyped (50K SNP) Canadian Holstein cattle from 283,817 parents-offspring trios. A total of 482 regions with TRD containing 671 positional genes were found. The functional analysis detected biological pathways associated with uterus development, embryonic skeletal system development, and nervous system development. Additionally, gene ontology terms from the topology-based pathway enrichment analysis were mostly related to the steroid hormones signalling pathway. Although difficult, genes specific to gametic incompatibility could be differentiated from genes underlying other reproduction processes by refining the genetic regions with TRD. With further investigation, we will provide new information to improve mate allocation for the dairy cattle industry.

scholarly journals Molecular and Comparative Genetics of Mental Retardation

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 835-881 ◽  
Author(s):  
Jennifer K Inlow ◽  
Linda L Restifo
Keyword(s):  
Mental Retardation ◽  
Homo Sapiens ◽  
System Development ◽  
Laboratory Data ◽  
Fruit Fly ◽  
Mendelian Inheritance ◽  
Nervous System Development ◽  
Skewed Distribution ◽  
Therapeutic Drug ◽  
Cellular Mechanisms

Abstract Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of >1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the ∼700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR.

scholarly journals Decoding molecular markers and transcriptional circuitry of naive and primed states of human pluripotency

2020 ◽  
Author(s):  
Arindam Ghosh ◽  
Anup Som
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
System Development ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
List Type ◽  
Metabolic Processes ◽  
Primed State

ABSTRACTPluripotent stem cells (PSCs) have been observed to occur in two distinct states — naive and primed. Both naive and primed state PSCs can give rise to tissues of all the three germ layers in vitro but differ in their potential to generate germline chimera in vivo. Understanding the molecular mechanisms that govern these two states of pluripotency in human can open up a plethora of opportunities for studying early embryonic development and in biomedical applications. In this work, we use weighted gene co-expression network (WGCN) approach to identify the key molecular makers and their interactions that define the two distinct pluripotency states. Signed-hybrid WGCN was reconstructed from transcriptomic data (RNA-seq) of naive and primed state pluripotent samples. Our analysis revealed two sets of genes that are involved in establishment and maintenance of naive (4791 genes) and primed (5066 genes) states. The naive state genes were found to be enriched for biological processes and pathways related to metabolic processes while primed state genes were associated with system development. Further, we identified the top 10% genes by intra-modular connectivity as hubs and the hub transcription factors for each group, thus providing a three-tier list of genes associated with naive and primed states of pluripotency in human.HIGHLIGHTSWeighted gene co-expression network analysis (WGCNA) identified 4791 and 5066 genes to be involved in naive and primed states of human pluripotency respectively.Functional and pathway enrichment analysis revealed the naive genes were mostly related to metabolic processes and primed genes to system development.The top 10% genes based on intra-modular connectivity from each group were defined as hubs.Identified 52 and 33 transcription factors among the naive and primed module hubs respectively.The transcription factors might play a switch on-off mechanism in induction of the two pluripotent states.

scholarly journals A Network Pharmacology Technique to Investigate the Synergistic Mechanisms of Salvia miltiorrhiza and Radix puerariae in Treatment of Cardio-Cerebral Vascular Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yang Ma ◽  
Wenjun Wang ◽  
Jiani Yang ◽  
Sha Zhang ◽  
Zhe Li ◽  
...  
Keyword(s):  
Drug Targets ◽  
Salvia Miltiorrhiza ◽  
Vascular Diseases ◽  
Enrichment Analysis ◽  
Mendelian Inheritance ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Ingredients ◽  
Radix Puerariae ◽  
Cerebral Vascular

Objective. This study is aimed to analyze the active ingredients, drug targets, and related pathways in the combination of Salvia miltiorrhiza (SM) and Radix puerariae (RP) in the treatment of cardio-cerebral vascular diseases (CCVDs). Method. The ingredients and targets of SM and RP were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the disease targets were obtained from Therapeutic Target Database (TTD), National Center for Biotechnology Information (NCBI), and Online Mendelian Inheritance in Man (OMIM) Database. The synergistic mechanisms of the SM and RP were evaluated by gene ontology (GO) enrichment analyses and Kyoto encyclopedia of genes and genomes (KEGG) path enrichment analyses. Result. A total of 61 active ingredients and 58 common targets were identified in this study. KEGG pathway enrichment analysis results showed that SM- and RP-regulated pathways were mainly inflammatory processes, immunosuppression, and cardiovascular systems. The component-target-pathway network indicated that SM and RP exert a synergistic mechanism for CCVDs through PTGS2 target in PI3k-Akt, TNF, and Jak-STAT signaling pathways. Conclusion. In summary, this study clarified the synergistic mechanisms of SM and RP, which can provide a better understanding of effect in the treatment of CCVDs.

scholarly journals Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Ndst Gene Function

2020 ◽  
Vol 8 (3) ◽  
pp. 13
Author(s):  
Lars Lewejohann ◽  
Srinivas R. Pallerla ◽  
Rebecca S. Schreiber ◽  
Joanna Gerula ◽  
Kay Grobe
Keyword(s):  
Purkinje Cell ◽  
Heparan Sulfate ◽  
Gene Function ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Reproductive Capacity ◽  
Cell Protein ◽  
Brain Physiology ◽  
Mutant Female

Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 (Ndst1) during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of Ndst function in adult brain physiology is less explored. Therefore, we generated mice bearing a Purkinje-cell-specific deletion in Ndst1 gene function by using Cre/loxP technology under the control of the Purkinje cell protein 2 (Pcp2/L7) promotor, which results in HS undersulfation. We observed that mutant mice did not show overt changes in the density or organization of Purkinje cells in the adult cerebellum, and behavioral tests also demonstrated normal cerebellar function. This suggested that postnatal Purkinje cell development and homeostasis are independent of Ndst1 function, or that impaired HS sulfation upon deletion of Ndst1 function may be compensated for by other Purkinje cell-expressed Ndst isoforms. To test the latter possibility, we additionally deleted the second Purkinje-cell expressed Ndst family member, Ndst2. This selectively abolished reproductive capacity of compound mutant female, but not male, mice, suggesting that ovulation, gestation, or female reproductive behavior specifically depends on Ndst-dependent HS sulfation in cells types that express Cre under Pcp2/L7 promotor control.

scholarly journals The proteomic architecture of schizophrenia iPSC-derived cerebral organoids reveals alterations in GWAS and neuronal development factors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Notaras ◽  
Aiman Lodhi ◽  
Haoyun Fang ◽  
David Greening ◽  
Dilek Colak
Keyword(s):  
High Throughput ◽  
Molecular Mechanisms ◽  
System Development ◽  
Early Adulthood ◽  
Enrichment Analysis ◽  
Nervous System Development ◽  
Model Systems ◽  
Proteomic Profiling ◽  
Human Brain Tissue ◽  
Brain Disorder

AbstractSchizophrenia (Scz) is a brain disorder that has a typical onset in early adulthood but otherwise maintains unknown disease origins. Unfortunately, little progress has been made in understanding the molecular mechanisms underlying neurodevelopment of Scz due to ethical and technical limitations in accessing developing human brain tissue. To overcome this challenge, we have previously utilized patient-derived Induced Pluripotent Stem Cells (iPSCs) to generate self-developing, self-maturating, and self-organizing 3D brain-like tissue known as cerebral organoids. As a continuation of this prior work, here we provide an architectural map of the developing Scz organoid proteome. Utilizing iPSCs from n = 25 human donors (n = 8 healthy Ctrl donors, and n = 17 Scz patients), we generated 3D cerebral organoids, employed 16-plex isobaric sample-barcoding chemistry, and simultaneously subjected samples to comprehensive high-throughput liquid-chromatography/mass-spectrometry (LC/MS) quantitative proteomics. Of 3,705 proteins identified by high-throughput proteomic profiling, we identified that just ~2.62% of the organoid global proteomic landscape was differentially regulated in Scz organoids. In sum, just 43 proteins were up-regulated and 54 were down-regulated in Scz patient-derived organoids. Notably, a range of neuronal factors were depleted in Scz organoids (e.g., MAP2, TUBB3, SV2A, GAP43, CRABP1, NCAM1 etc.). Based on global enrichment analysis, alterations in key pathways that regulate nervous system development (e.g., axonogenesis, axon development, axon guidance, morphogenesis pathways regulating neuronal differentiation, as well as substantia nigra development) were perturbed in Scz patient-derived organoids. We also identified prominent alterations in two novel GWAS factors, Pleiotrophin (PTN) and Podocalyxin (PODXL), in Scz organoids. In sum, this work serves as both a report and a resource that researchers can leverage to compare, contrast, or orthogonally validate Scz factors and pathways identified in observational clinical studies and other model systems.

scholarly journals The Proteomic Architecture of Schizophrenia Cerebral Organoids Reveals Alterations in GWAS and Neuronal Development Factors

2021 ◽  
Author(s):  
Michael Notaras ◽  
Aiman Lodhi ◽  
Haoyun Fang ◽  
David Greening ◽  
Dilek Colak
Keyword(s):  
High Throughput ◽  
Molecular Mechanisms ◽  
System Development ◽  
Early Adulthood ◽  
Enrichment Analysis ◽  
Nervous System Development ◽  
Model Systems ◽  
Proteomic Profiling ◽  
Human Brain Tissue ◽  
Brain Disorder

Schizophrenia (Scz) is a brain disorder that has a typical onset in early adulthood but otherwise maintains unknown disease origins. Unfortunately, little progress has been made in understanding the molecular mechanisms underlying neurodevelopment of Scz due to ethical and technical limitations in accessing developing human brain tissue. To overcome this challenge, we have previously utilized patient-derived Induced Pluripotent Stem Cells (iPSCs) to generate self-developing, self-maturating, and self-organizing 3D brain-like tissue known as cerebral organoids. As a continuation of this prior work [1], here we provide a molecular architectural map of the developing Scz organoid proteome. Utilizing iPSCs from n = 25 human donors (n = 8 healthy Ctrl donors, and n = 17 Scz patients), we generated 3D human cerebral organoids, employed 16-plex isobaric sample-barcoding chemistry, and simultaneously subjected samples to comprehensive high-throughput liquid-chromatography/mass-spectrometry (LC/MS) quantitative proteomics. Of 3,705 proteins identified by high-throughput proteomic profiling, we identified that just ~2.62% of the organoid global proteomic landscape was differentially regulated in Scz organoids. In sum, just 43 proteins were up-regulated and 54 were down-regulated in Scz patient-derived organoids. Notably, a range of neuronal factors were depleted in Scz organoids (e.g., MAP2, TUBB3, SV2A, GAP43, CRABP1, NCAM1 etc.). Based on global enrichment analysis, alterations in key pathways that regulate nervous system development (e.g., axonogenesis, axon development, axon guidance, morphogenesis pathways regulating neuronal differentiation, as well as substantia nigra development) were perturbed in Scz patient-derived organoids. We also identified prominent alterations in two novel GWAS factors, Pleiotrophin (PTN) and Podocalyxin (PODXL), in Scz organoids. In sum, this work serves as both a report and a resource whereby researchers can leverage human-derived neurodevelopmental data from Scz patients, which can be used to mine, compare, contrast, or orthogonally validate novel factors and pathways related to Scz risk identified in datasets from observational clinical studies and other model systems.

scholarly journals RNA sequencing data integration reveals an miRNA interactome of osteoarthritis cartilage

2018 ◽  
Vol 78 (2) ◽  
pp. 270-277 ◽  
Author(s):  
Rodrigo Coutinho de Almeida ◽  
Yolande F M Ramos ◽  
Ahmed Mahfouz ◽  
Wouter den Hollander ◽  
Nico Lakenberg ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Messenger Rna ◽  
Enrichment Analysis ◽  
Integrated Approach ◽  
Nervous System Development ◽  
Regulatory Mechanisms ◽  
Pathway Enrichment Analysis ◽  
Sequencing Data ◽  
Pathway Enrichment ◽  
Mrna Targets

ObjectiveTo uncover the microRNA (miRNA) interactome of the osteoarthritis (OA) pathophysiological process in the cartilage.MethodsWe performed RNA sequencing in 130 samples (n=35 and n=30 pairs for messenger RNA (mRNA) and miRNA, respectively) on macroscopically preserved and lesioned OA cartilage from the same patient and performed differential expression (DE) analysis of miRNA and mRNAs. To build an OA-specific miRNA interactome, a prioritisation scheme was applied based on inverse Pearson’s correlations and inverse DE of miRNAs and mRNAs. Subsequently, these were filtered by those present in predicted (TargetScan/microT-CDS) and/or experimentally validated (miRTarBase/TarBase) public databases. Pathway enrichment analysis was applied to elucidate OA-related pathways likely mediated by miRNA regulatory mechanisms.ResultsWe found 142 miRNAs and 2387 mRNAs to be differentially expressed between lesioned and preserved OA articular cartilage. After applying prioritisation towards likely miRNA-mRNA targets, a regulatory network of 62 miRNAs targeting 238 mRNAs was created. Subsequent pathway enrichment analysis of these mRNAs (or genes) elucidated that genes within the ‘nervous system development’ are likely mediated by miRNA regulatory mechanisms (familywise error=8.4×10−5). Herein NTF3 encodes neurotrophin-3, which controls survival and differentiation of neurons and which is closely related to the nerve growth factor.ConclusionsBy an integrated approach of miRNA and mRNA sequencing data of OA cartilage, an OA miRNA interactome and related pathways were elucidated. Our functional data demonstrated interacting levels at which miRNA affects expression of genes in the cartilage and exemplified the complexity of functionally validating a network of genes that may be targeted by multiple miRNAs.

scholarly journals Investigation of the Mechanisms of Chuankezhi Injection in the Treatment of Asthma Based on the Network Pharmacology Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hao Zhu ◽  
Yuhuan Shi ◽  
Shanshan Jiang ◽  
Xiuxiu Jiao ◽  
Hui Zhu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Enrichment Analysis ◽  
Mendelian Inheritance ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
China National Knowledge Infrastructure ◽  
Overlapping Gene ◽  
Gene Symbols

Background. Chuankezhi injection (CKZI) was an effective traditional Chinese medicine (TCM) injection in adjuvant bronchial asthma therapy. In this report, we used a network pharmacology method to reveal the mechanisms of CKZI for the treatment of asthma. Methods. The candidate compounds in CKZI were determined by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and China National Knowledge Infrastructure website (CNKI). The targets of candidate compounds were searched in the TCMSP, DrugBank 5.0, and SwissTargetPrediction. The disease targets were screened from the Online Mendelian Inheritance in Man (OMIM) and GeneCards. The overlapping gene symbols between candidate compounds and disease were filtered via a Venn diagram and were considered as potential targets. A protein-protein interaction (PPI) network and disease-related candidate compound-target-pathway (DC-T-P) network were visualized by Cytoscape 3.6.1. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by metascape to determine the pathways related to asthma. Results. A total of 70 overlapping gene symbols were recognized as potential targets. Cytokines (IL6, TNF, and IL1B) and chemokines (CXCL8 and CCL2) could be recognized as hub genes. Asthma-related candidate compounds were mainly flavonoids, such as quercetin, luteolin, and kaempferol. The cytokine-mediated signaling pathway, cytokine receptor binding, and membrane craft were the most significant biological process (BP), molecular function (MF), and cellular component (CC) of GO function results, respectively. The relevant pathways of CKZI against asthma mainly include IL-17, NF-kappa B, HIF-1, calcium, and PI3K-Akt signaling pathways. Conclusion. Our research provided a theoretical basis for further investigating the mechanisms of CKZI in the treatment of asthma.

scholarly journals Intergenerational neurocognitive effects of intrauterine hyperglycemia on male offspring

2020 ◽  
Author(s):  
Kexin Zou ◽  
Jun Ren ◽  
Junyu Zhang ◽  
Chengliang Zhou ◽  
Sisi Luo ◽  
...  
Keyword(s):  
Germ Line ◽  
System Development ◽  
Enrichment Analysis ◽  
Transcriptome Profiling ◽  
Nervous System Development ◽  
Male Offspring ◽  
Gene Set Enrichment Analysis ◽  
Epigenetic Mechanism ◽  
Molecular Defects ◽  
Major Player

Abstract Background Studies on human and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, researches have focused on the neurodevelopment consequences of the first filial (F1) offspring. We hypothesize that the intrauterine hyperglycemia exposure will alter epigenetic reprogramming in F1 sperm, and carry risks of passing on molecular defects to the second filial (F2). Results We found that intrauterine hyperglycemia exposure resulted in memory impairment in both F1 and F2 males from the F1-GDM male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes were enriched in learning, memory, cognition, neurotransmission, synaptic plasticity, and postsynaptic specialization. Again, enrichment curves computed by Gene set enrichment analysis (GSEA) of F1 hippocampi were highly consistent with F2. Interestingly, combined analysis of F1 sperm methylome and gene expression of F2 hippocampi screened out several hypermethylation-low expression genes which are associated with abnormal central nervous system development (particularly synapse development and homeostasis), such as Camk2b, Dlgap1, Wnt5a, Tubb2b and so on. Conclusions These findings implicate that the male germ line is a major player in transgenerational phenotypic transmission. Taken together, our results for the first time suggest that intrauterine hyperglycemia leads to transgenerational cognitive impairment, and, sperm methylome is a potential epigenetic mechanism for the effects of GDM.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

Sign in / Sign up

Export Citation Format

Share Document