scholarly journals A genome-wide genetic screen uncovers novel determinants of human pigmentation

2021 ◽  
Author(s):  
Vivek K Bajpai ◽  
Tomek Swigut ◽  
Jaaved Mohammed ◽  
Josh Tycko ◽  
Sahin Naqvi ◽  
...  
Keyword(s):  
Cell Biology ◽  
Skin Color ◽  
Color Variation ◽  
Potential Contribution ◽  
Posttranscriptional Gene Regulation ◽  
Novel Approach ◽  
Genome Wide ◽  
A Genome ◽  
Endosomal Transport ◽  
Functionally Diverse

The skin color is one of the most diverse human traits and is determined by the quantity, type and distribution of melanin. Here, we leverage light scattering properties of melanin to conduct a genome-wide CRISPR-Cas9 screen for novel regulators of melanogenesis. We identify functionally diverse genes converging on melanosome biogenesis, endosomal transport and transcriptional/posttranscriptional gene regulation, most of which represent novel associations with pigmentation. A survey of transcriptomes from diversely pigmented individuals reveals that the majority of genes discovered in our screen are upregulated in dark skin melanocytes, in agreement with their melanin-promoting function and potential contribution to skin color variation. This association is further buttressed by the significant skin color heritability enrichment in the vicinity of these genes. Taken together, our study presents a novel approach to assay pigmentation and uncovers a plethora of melanogenesis regulators, with broad implications for human variation, cell biology and medicine.

scholarly journals A Genome-Wide Association Study Identifies the Skin Color Genes IRF4 , MC1R , ASIP , and BNC2 Influencing Facial Pigmented Spots

2015 ◽  
Vol 135 (7) ◽  
pp. 1735-1742 ◽  
Author(s):  
Leonie C. Jacobs ◽  
Merel A. Hamer ◽  
David A. Gunn ◽  
Joris Deelen ◽  
Jaspal S. Lall ◽  
...  
Keyword(s):  
Association Study ◽  
Skin Color ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color

2019 ◽  
Author(s):  
Hanna Helgeland ◽  
Marte Sodeland ◽  
Nina Zoric ◽  
Jacob Seilø Torgersen ◽  
Fabian Grammes ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Beta Carotene ◽  
Color Variation ◽  
Flesh Color ◽  
Functional Studies ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Mrna And Protein Expression

AbstractRed coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL-region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, several functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

scholarly journals PRMT5 promotes cancer cell migration and invasion through the E2F pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wojciech Barczak ◽  
Li Jin ◽  
Simon Mark Carr ◽  
Shonagh Munro ◽  
Samuel Ward ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Cell Biology ◽  
Arginine Methylation ◽  
Migration And Invasion ◽  
Genome Wide ◽  
A Genome ◽  
Important Pathway ◽  
Major Target

Abstract The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.

scholarly journals Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hanna Helgeland ◽  
Marte Sodeland ◽  
Nina Zoric ◽  
Jacob Seilø Torgersen ◽  
Fabian Grammes ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Beta Carotene ◽  
Color Variation ◽  
Flesh Color ◽  
Functional Studies ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Mrna And Protein Expression

AbstractRed coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL- region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

scholarly journals Genetics of skin color variation in Europeans: genome-wide association studies with functional follow-up

2015 ◽  
Vol 134 (8) ◽  
pp. 823-835 ◽  
Author(s):  
Fan Liu ◽  
Mijke Visser ◽  
David L. Duffy ◽  
Pirro G. Hysi ◽  
Leonie C. Jacobs ◽  
...  
Keyword(s):  
Skin Color ◽  
Association Studies ◽  
Color Variation ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

Skin Color Correction for Tissue Spectroscopy: Demonstration of a Novel Approach with Tissue-Mimicking Phantoms

2005 ◽  
Vol 59 (2) ◽  
pp. 237-244 ◽  
Author(s):  
Olusola O. Soyemi ◽  
Michelle R. Landry ◽  
Ye Yang ◽  
Patrick O. Idwasi ◽  
Babs R. Soller
Keyword(s):  
Skin Color ◽  
Near Infrared ◽  
Skin Pigmentation ◽  
Nir Spectroscopy ◽  
Bottom Layer ◽  
Correction Method ◽  
Color Variation ◽  
Absorption Properties ◽  
Novel Approach ◽  
Components Analysis

The application of partial least squares (PLS) regression to visible–near-infrared (VIS-NIR) spectroscopy for modeling important blood and tissue parameters is generally complicated by the variation in skin pigmentation (melanin) across the human population. An orthogonal correction method for removing the influence of skin pigmentation has been demonstrated in diffuse reflectance spectra from two-layer tissue-mimicking phantoms. The absorption properties of the phantoms were defined by lyophilized human hemoglobin (bottom layer) and synthetic melanin (top layer). Tissue-like scattering was simulated in both layers with intralipid™. The approach uses principal components analysis (PCA) loading vectors from a separate set of phantom spectra that encode the unwanted melanin variation to remove the effect of melanin from the test phantoms. The preprocessing of phantom spectra using this orthogonal correction method resulted in PLS models with reduced complexity and enhanced prediction performance. Preliminary results from a separate study that evaluates the feasibility of defining skin color variation in an experiment with a single human subject are also presented.

scholarly journals A genome-wide RNAi screen reveals multiple regulators of caspase activation

2007 ◽  
Vol 179 (4) ◽  
pp. 619-626 ◽  
Author(s):  
Caroline H. Yi ◽  
Dodzie K. Sogah ◽  
Michael Boyce ◽  
Alexei Degterev ◽  
Dana E. Christofferson ◽  
...  
Keyword(s):  
Cell Death ◽  
Mammalian Cells ◽  
Caspase Activation ◽  
Functional Conservation ◽  
Cellular Processes ◽  
Regulatory Circuits ◽  
Genome Wide ◽  
A Genome ◽  
Dependent Cell ◽  
Functionally Diverse

Apoptosis is an evolutionally conserved cellular suicide mechanism that can be activated in response to a variety of stressful stimuli. Increasing evidence suggests that apoptotic regulation relies on specialized cell death signaling pathways and also integrates diverse signals from additional regulatory circuits, including those of cellular homeostasis. We present a genome-wide RNA interference screen to systematically identify regulators of apoptosis induced by DNA damage in Drosophila melanogaster cells. We identify 47 double- stranded RNA that target a functionally diverse set of genes, including several with a known function in promoting cell death. Further characterization uncovers 10 genes that influence caspase activation upon the removal of Drosophila inhibitor of apoptosis 1. This set includes the Drosophila initiator caspase Dronc and, surprisingly, several metabolic regulators, a candidate tumor suppressor, Charlatan, and an N-acetyltransferase, ARD1. Importantly, several of these genes show functional conservation in regulating apoptosis in mammalian cells. Our data suggest a previously unappreciated fundamental connection between various cellular processes and caspase-dependent cell death.

scholarly journals SNPs and GVHD prediction: where to next?

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5066-5068 ◽  
Author(s):  
Anne M. Dickinson
Keyword(s):  
Genome Wide Association Study ◽  
Snp Array ◽  
Candidate Snps ◽  
Cell Transplant ◽  
Nucleotide Polymorphisms ◽  
Hematopoietic Stem ◽  
Novel Approach ◽  
Genome Wide ◽  
Impute Data ◽  
A Genome

The article by Chien at al in this issue of Blood uses a novel approach to assess the role of single nucleotide polymorphisms (SNPs) in acute graft-versus-host disease (GVHD). Using a genome-wide association study (GWAS) employing an Affymetrix GeneChip Genome-Wide Human 500 000 SNP array, they screened 1298 allogeneic hematopoietic stem cell transplant donors and recipients and tested whether the results from 40 previously reported candidate SNPs could be replicated. They also used a novel approach to impute data using IMPUTE software (http://nathgen.stats-ox.ac.uk/impute/impute.html) where the genotyping data were not available.1

scholarly journals Quantitative interactions: the disease outcome of Botrytis cinerea across the plant kingdom

2021 ◽  
Author(s):  
Celine Caseys ◽  
Gongjun Shi ◽  
Nicole Soltis ◽  
Raoni Gwinner ◽  
Jason Corwin ◽  
...  
Keyword(s):  
Botrytis Cinerea ◽  
Host Specificity ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
Disease Outcome ◽  
Plant Kingdom ◽  
Pathogen Virulence ◽  
Genome Wide ◽  
A Genome ◽  
Functionally Diverse

Abstract Botrytis cinerea is a fungal pathogen that causes necrotic disease on more than a thousand known hosts widely spread across the plant kingdom. How B. cinerea interacts with such extensive host diversity remains largely unknown. To address this question, we generated an infectivity matrix of 98 strains of B. cinerea on 90 genotypes representing eight host plants. This experimental infectivity matrix revealed that the disease outcome is largely explained by variations in either the host resistance or pathogen virulence. However, the specific interactions between host and pathogen account for 16% of the disease outcome. Furthermore, the disease outcomes cluster among genotypes of a species but are independent of the relatedness between hosts. When analyzing the host specificity and virulence of B. cinerea, generalist strains are predominant. In this fungal necrotroph, specialization may happen by a loss in virulence on most hosts rather than an increase of virulence on a specific host. To uncover the genetic architecture of Botrytis host specificity and virulence, a genome-wide association study (GWAS) was performed and revealed up to 1492 genes of interest. The genetic architecture of these traits is widespread across B. cinerea genome. The complexity of the disease outcome might be explained by hundreds of functionally diverse genes putatively involved in adjusting the infection to diverse hosts.

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