When Bigger Is Better: 3D RNA Profiling of the Developing Head in the Catshark Scyliorhinus canicula

We report the adaptation of RNA tomography, a technique allowing spatially resolved, genome-wide expression profiling, to a species occupying a key phylogenetic position in gnathostomes, the catshark Scyliorhinus canicula. We focused analysis on head explants at an embryonic stage, shortly following neural tube closure and of interest for a number of developmental processes, including early brain patterning, placode specification or the establishment of epithalamic asymmetry. As described in the zebrafish, we have sequenced RNAs extracted from serial sections along transverse, horizontal and sagittal planes, mapped the data onto a gene reference taking advantage of the high continuity genome recently released in the catshark, and projected read counts onto a digital model of the head obtained by confocal microscopy. This results in the generation of a genome-wide 3D atlas, containing expression data for most protein-coding genes in a digital model of the embryonic head. The digital profiles obtained for candidate forebrain regional markers along antero-posterior, dorso-ventral and left-right axes reproduce those obtained by in situ hybridization (ISH), with expected relative organizations. We also use spatial autocorrelation and correlation as measures to analyze these data and show that they provide adequate statistical tools to extract novel expression information from the model. These data and tools allow exhaustive searches of genes exhibiting any predefined expression characteristic, such a restriction to a territory of interest, thus providing a reference for comparative analyses across gnathostomes. This methodology appears best suited to species endowed with large embryo or organ sizes and opens novel perspectives to a wide range of evo-devo model organisms, traditionally counter-selected on size criterion.

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A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genes ◽

10.3390/genes12050643 ◽

2021 ◽

Vol 12 (5) ◽

pp. 643

Author(s):

Thibaud Kuca ◽

Brandy M. Marron ◽

Joana G. P. Jacinto ◽

Julia M. Paris ◽

Christian Gerspach ◽

...

Keyword(s):

Genome Wide Association Study ◽

Homozygosity Mapping ◽

Mendelian Inheritance ◽

Large Animal Model ◽

Large Animal ◽

Loss Of Function ◽

Protein Coding ◽

Positional Candidate ◽

Genome Wide ◽

A Genome

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).

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The Genetics and Genomics of Asthma

Annual Review of Genomics and Human Genetics ◽

10.1146/annurev-genom-083117-021651 ◽

2018 ◽

Vol 19 (1) ◽

pp. 223-246 ◽

Cited By ~ 14

Author(s):

Saffron A.G. Willis-Owen ◽

William O.C. Cookson ◽

Miriam F. Moffatt

Keyword(s):

Sequence Variation ◽

Human Microbiome ◽

Technological Advances ◽

Genome Wide ◽

A Genome ◽

Wide Range ◽

Health And Disease ◽

Wide Scale ◽

Genetics And Genomics ◽

The Individual

Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis—assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale—have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.

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From conservation genetics to conservation genomics: a genome-wide assessment of blue whales ( Balaenoptera musculus ) in Australian feeding aggregations

Royal Society Open Science ◽

10.1098/rsos.170925 ◽

2018 ◽

Vol 5 (1) ◽

pp. 170925 ◽

Cited By ~ 10

Author(s):

Catherine R. M. Attard ◽

Luciano B. Beheregaray ◽

Jonathan Sandoval-Castillo ◽

K. Curt S. Jenner ◽

Peter C. Gill ◽

...

Keyword(s):

Population Structure ◽

Adaptive Divergence ◽

Balaenoptera Musculus ◽

Blue Whale ◽

Conservation Genomics ◽

Next Generation Sequencing Technology ◽

Genome Wide ◽

A Genome ◽

Wide Range ◽

Blue Whales

Genetic datasets of tens of markers have been superseded through next-generation sequencing technology with genome-wide datasets of thousands of markers. Genomic datasets improve our power to detect low population structure and identify adaptive divergence. The increased population-level knowledge can inform the conservation management of endangered species, such as the blue whale ( Balaenoptera musculus ). In Australia, there are two known feeding aggregations of the pygmy blue whale ( B. m. brevicauda ) which have shown no evidence of genetic structure based on a small dataset of 10 microsatellites and mtDNA. Here, we develop and implement a high-resolution dataset of 8294 genome-wide filtered single nucleotide polymorphisms, the first of its kind for blue whales. We use these data to assess whether the Australian feeding aggregations constitute one population and to test for the first time whether there is adaptive divergence between the feeding aggregations. We found no evidence of neutral population structure and negligible evidence of adaptive divergence. We propose that individuals likely travel widely between feeding areas and to breeding areas, which would require them to be adapted to a wide range of environmental conditions. This has important implications for their conservation as this blue whale population is likely vulnerable to a range of anthropogenic threats both off Australia and elsewhere.

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A porcine brain-wide RNA editing landscape

10.21203/rs.3.rs-110949/v1 ◽

2020 ◽

Author(s):

Jinrong Huang ◽

Lin Lin ◽

Zhanying Dong ◽

Ling Yang ◽

Tianyu Zheng ◽

...

Keyword(s):

Rna Editing ◽

Repetitive Sequences ◽

Brain Regions ◽

Mammalian Brain ◽

Protein Coding ◽

Porcine Brain ◽

Coding Regions ◽

Pig Brain ◽

Genome Wide ◽

A Genome

Abstract Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is an essential post-transcriptional modiﬁcation. Although hundreds of thousands of RNA editing sites have been reported in mammals, brain-wide analysis of the RNA editing in the mammalian brain remains rare. Here, a genome-wide RNA editing investigation is performed in 119 samples, representing 30 anatomically defined subregions in the pig brain. We identify a total of 682,037 A-to-I RNA editing sites of which 97% are not identified before. Within the pig brain, cerebellum and olfactory bulb are regions with most edited transcripts. The editing level of sites residing in protein-coding regions are similar across brain regions, whereas region-distinct editing is observed in repetitive sequences. Highly edited conserved recoding events in pig and human brain are found in neurotransmitter receptors, demonstrating the evolutionary importance of RNA editing in neurotransmission functions. The porcine brain-wide RNA landscape provides a rich resource to better understand the evolutionally importance of post-transcriptional RNA editing.

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Genome-wide identification of SSR markers in the Brassica A genome and their utility in breeding

Canadian Journal of Plant Science ◽

10.1139/cjps-2015-0250 ◽

2016 ◽

Vol 96 (5) ◽

pp. 808-818 ◽

Cited By ~ 4

Author(s):

Neil Hobson ◽

Habibur Rahman

Keyword(s):

Genetic Diversity ◽

Ssr Markers ◽

Low Cost ◽

Pak Choi ◽

Genome Wide ◽

A Genome ◽

Wide Range ◽

Genetic Pools ◽

High Level ◽

Simple Sequence

Simple sequence repeat (SSR) markers can be applied to genotyping projects at low cost with inexpensive equipment. The objective of this study was to develop SSR markers from the publically-available genome sequence of Brassica rapa and provide the physical position of these markers on the chromosomes for use in breeding and research. To assess the utility of these new markers, a subset of 60 markers were used to genotype 43 accessions of B. rapa. Fifty-five markers from the 10 chromosome scaffolds produced a total of 730 amplicons, which were then used to perform a phylogenetic analysis of the accessions, illustrating their utility in distinguishing between a wide range of germplasm. In agreement with similar studies of genetic diversity, our markers separated accessions into distinct genetic pools including Chinese cabbage, Chinese winter oilseed, European winter oilseed, Canadian spring oilseed, pak-choi, turnip, and yellow sarson. The results further illustrate the presence of a high level of genetic diversity in B. rapa, and demonstrate the potential of these SSR markers for use in breeding and research.

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The maternal environment interacts with genetic variation in regulating seed dormancy in Arabidopsis thaliana

10.1101/117879 ◽

2017 ◽

Author(s):

Envel Kerdaffrec ◽

Magnus Nordborg

Keyword(s):

Arabidopsis Thaliana ◽

Association Study ◽

Seed Dormancy ◽

Genome Wide Association Study ◽

Seed Maturation ◽

Genome Wide Association ◽

Maternal Environment ◽

Genome Wide ◽

A Genome ◽

Wide Range

AbstractSeed dormancy is a complex adaptive trait that controls the timing of seed germination, one of the major fitness components in many plant species. Despite being highly heritable, seed dormancy is extremely plastic and influenced by a wide range of environmental cues. Here, using a set of 92 Arabidopsis thaliana lines from Sweden, we investigate the effect of seed maturation temperature on dormancy variation at the population level. The response to temperature differs dramatically between lines, demonstrating that genotype and the maternal environment interact in controlling the trait. By performing a genome-wide association study (GWAS), we identified several candidate genes that could account for this plasticity, two of which are involved in the photoinduction of germination. Altogether, our results provide insight into both the molecular mechanisms and the evolution of dormancy plasticity, and can serve to improve our understanding of environmentally dependent life-history transitions.HighlightThe effect of low seed-maturation temperatures on seed dormancy is highly variable in Arabidopsis thaliana accessions from Sweden, denoting strong genotype-environment interactions, and a genome-wide association study identified compelling candidates that could account for this plasticity.

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Genome-wide Association Study of Anxiety and Stress-related Disorders in the iPSYCH Cohort

10.1101/263855 ◽

2018 ◽

Cited By ~ 9

Author(s):

Sandra M. Meier ◽

Kalevi Trontti ◽

Thomas Damm Als ◽

Mikaela Laine ◽

Marianne Giørtz Pedersen ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Common Mental Disorders ◽

Twin Studies ◽

Genome Wide Association ◽

Sensitivity Analyses ◽

Association Analyses ◽

Genome Wide ◽

A Genome ◽

Wide Range

AbstractAnxiety and stress-related disorders (ASRD) are among the most common mental disorders with the majority of patients suffering from additional disorders. Family and twin studies indicate that genetic and environmental factors are underlying their etiology. As ASRD are likely to configure various expressions of abnormalities in the basic stress-response system, we conducted a genome-wide association study including 12,655 cases with various anxiety and stress-related diagnoses and 19,225 controls. Standard association analyses were performed supplemented by a framework of sensitivity analyses. Variants in PDE4B showed consistent association with ASRD across a wide range of our analyses. In mice models, alternations in PDE4B expression were observed in those mice displaying anxious behavior after exposure to chronic stress. We also showed that 28% of the variance in ASRD was accounted for by common variants and that the genetic signature of ASRD overlapped with psychiatric traits, educational outcomes, obesity-related phenotypes, smoking, and reproductive success.

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Host cell factors important for BHV-1 cell entry revealed by genome-wide CRISPR knockout screen

10.1101/2020.06.18.160523 ◽

2020 ◽

Author(s):

Wenfang Spring Tan ◽

Enguang Rong ◽

Inga Dry ◽

Simon Lillico ◽

Andy Law ◽

...

Keyword(s):

Host Cell ◽

Viral Entry ◽

Surface Proteins ◽

Chain Elongation ◽

Related Factors ◽

Protein Coding ◽

Cog Complex ◽

Genome Wide ◽

A Genome ◽

Mdbk Cells

AbstractIn order to identify host factors that impact Bovine Herpes Virus Type 1 (BHV-1) infection we previously applied a genome wide CRISPR knockout screen with a library covering all bovine protein coding genes. We compiled a list of both pro-viral and anti-viral proteins involved in BHV-1 replication; here we provide further analysis of those that are potentially involved in viral entry into the host cell. These entry related factors include the cell surface proteins PVR and PVRL2, a group of enzymes directly or indirectly associated with the biosynthesis of Heparan Sulfate Proteoglycans (HSPG), and proteins that reside in the Golgi apparatus engaging in intra-Golgi trafficking. For the first time, we provide evidence that PVRL2 serves a receptor for BHV-1, mediating more efficient entry than the previously identified PVR. By knocking out two enzymes that catalyze HSPG chain elongation, HST2ST1 and GLCE, we demonstrated the significance of HSPG in BHV-1 entry. Another intriguing cluster of genes, COG1, COG2 and COG4-7 encodes for six subunits of the conserved oligomeric Golgi (COG) complex. MDBK cells lacking COG6 were less infectable by BHV-1 but release newly produced virions more efficiently as evidenced by fewer but bigger plaques compared to control cells, suggesting impaired HSPG biosynthesis. To facilitate candidate validation, we devised a one-step multiplex CRISPR interference (CRISPRi) system named CRISPR3i that enables quick and simultaneous deployment of three CRISPRs for efficient gene inactivation. Using CRISPR3i, we verified an additional 23 candidates, with many implicated in cellular entry.

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Genome-wide sexually antagonistic variants reveal longstanding constraints on sexual dimorphism in the fruitfly

10.1101/117176 ◽

2017 ◽

Cited By ~ 1

Author(s):

Filip Ruzicka ◽

Mark S. Hill ◽

Tanya M. Pennell ◽

Ilona Flis ◽

Fiona C. Ingleby ◽

...

Keyword(s):

Sexual Dimorphism ◽

Evolutionary Dynamics ◽

Genome Wide Association Study ◽

Balancing Selection ◽

Sexual Antagonism ◽

Protein Coding ◽

Genome Wide ◽

Genomic Location ◽

Classic Theory ◽

A Genome

The evolution of sexual dimorphism is constrained by a shared genome, leading to ‘sexual antagonism’ where different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal D. melanogaster fly lines to perform a genome-wide association study of sexual antagonism. We identify ~230 chromosomal clusters of candidate antagonistic SNPs. In contradiction to classic theory, we find no clear evidence that the X chromosome is a hotspot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range, indicating widespread and evolutionarily persistent (>10,000 years) genomic constraints. Based on our results, we propose that antagonistic variation accumulates due to constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation.

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Genome-wide Small Rna Profiling Reveals Tiller Development in Tall Fescue (Festuca Arundinacea Schreb.)

10.21203/rs.3.rs-27724/v1 ◽

2020 ◽

Author(s):

Tao Hu ◽

Tao Wang ◽

Huiying Li ◽

Misganaw Wassie ◽

Liang Chen

Keyword(s):

Production Rate ◽

Small Rna ◽

Tall Fescue ◽

Festuca Arundinacea ◽

Target Genes ◽

Cool Season ◽

Rna Profiling ◽

Mirna Genes ◽

Genome Wide ◽

A Genome

Abstract Background: Tall fescue (Festuca arundinacea Schreb.) is a major cool-season forage and turfgrass species. The low tiller density and size dramatically limits its turf performance and forage yield. MicroRNAs (miRNA)-genes modules play critical roles in tiller development in plants. In this study, a genome-wide small RNA profiling was carried out in two tall fescue genotypes contrasting for tillering production (‘Ch-3’, high tiller production rate and ‘Ch-5’, low tiller production rate) andtwo types of tissue samples at different tillering development stage (Pre-tillering, grass before tillering; Tillering, grass after tillering). ‘Ch-3’, ‘Ch-5’, Pre-tillering, and Tillering samples were analyzed using high-throughput RNA sequencing.Results: A total of 222 million high-quality clean reads were generated and 208 miRNAs were discovered, including 148 known miRNAs belonging to 70 families and 60 novel ones. Furthermore, 18 miRNAs were involved in tall fescue tiller development process. Among them, 14 miRNAs displayed increased abundance in both Ch-3 and Tillering plants compared with that in Ch-5 and Pre-tillering plants and were positive with tillering, while another four miRNAs were negative with tiller development. Out ofthe three miRNAs osa-miR156a, zma-miR528a-3p and osa-miR444b.2, the rest of 15 miRNAs were newfound controllers mediating tiller development in plants. Based on our previous full-length transcriptome analysis in tall fescue, 2 8927 potential target genes were discoveredfor all identified miRNAs. Most of the 212 target genes of the 18 miRNAs were dominantly enriched into “ubiquitin-mediated proteolysis”, “phagosome”, “fatty acid biosynthesis”, “oxidative phosphorylation”, and “biosynthesis of unsaturated fatty acids” KEGG pathways.Conclusions: This is the first genome-wide miRNA profiles analysis to identifyregulators involved in tiller development in cool-season turfgrass. Tillering related 18 miRNAs and their 212 target genes provide novel information for the understanding of the molecular mechanisms of miRNA-genes mediated tiller development in cool-season turfgrass.

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