LIVIVO - Search results -

Search results

Result 1 - 10 of total 15

Search options

Article ; Online: Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals.

Jagoda, Evelyn / Marnetto, Davide / Senevirathne, Gayani / Gonzalez, Victoria / Baid, Kaushal / Montinaro, Francesco / Richard, Daniel / Falzarano, Darryl / LeBlanc, Emmanuelle V / Colpitts, Che C / Banerjee, Arinjay / Pagani, Luca / Capellini, Terence D

eLife

2023 Volume 12

Abstract: Individuals infected with ... ...

Abstract	Individuals infected with the
MeSH term(s)	Humans ; Animals ; COVID-19/genetics ; Neanderthals/genetics ; SARS-CoV-2/genetics ; Virus Diseases ; Genetics, Population
Language	English
Publishing date	2023-02-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.71235
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals

Evelyn Jagoda / Davide Marnetto / Gayani Senevirathne / Victoria Gonzalez / Kaushal Baid / Francesco Montinaro / Daniel Richard / Darryl Falzarano / Emmanuelle V LeBlanc / Che C Colpitts / Arinjay Banerjee / Luca Pagani / Terence D Capellini

eLife, Vol

2023 Volume 12

Abstract: Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via ... ...

Abstract	Individuals infected with the SARS-CoV-2 virus present with a wide variety of symptoms ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe response to COVID-19. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the genetic predisposition to severe COVID-19 outcomes. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform a locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify four introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. Using reporter assays in the presence/absence of SARS-CoV-2, we find evidence that these variants respond to viral infection. These variants likely drive the locus’ impact on severity by modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.
Keywords	MPRA ; COVID-19 ; Neandertal introgression ; cis-regulation ; CCR1 ; CCR5 ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Compatibility rules of human enhancer and promoter sequences.

Bergman, Drew T / Jones, Thouis R / Liu, Vincent / Ray, Judhajeet / Jagoda, Evelyn / Siraj, Layla / Kang, Helen Y / Nasser, Joseph / Kane, Michael / Rios, Antonio / Nguyen, Tung H / Grossman, Sharon R / Fulco, Charles P / Lander, Eric S / Engreitz, Jesse M

Nature

2022 Volume 607, Issue 7917, Page(s) 176–184

Abstract: Gene regulation in the human genome is controlled by distal enhancers that activate specific nearby ... ...

Abstract	Gene regulation in the human genome is controlled by distal enhancers that activate specific nearby promoters
MeSH term(s)	Enhancer Elements, Genetic/genetics ; Humans ; Promoter Regions, Genetic/genetics ; RNA/biosynthesis ; RNA/genetics ; Transcription Factors/metabolism
Chemical Substances	Transcription Factors ; RNA (63231-63-0)
Language	English
Publishing date	2022-05-20
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-04877-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Dietary Variation and Evolution of Gene Copy Number among Dog Breeds.

Reiter, Taylor / Jagoda, Evelyn / Capellini, Terence D

PloS one

2016 Volume 11, Issue 2, Page(s) e0148899

Abstract: Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive ... ...

Abstract	Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic α-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Animal Feed ; Animals ; Carbohydrate Metabolism ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Diet ; Dogs/genetics ; Evolution, Molecular ; Gene Dosage ; Mixed Function Oxygenases/genetics ; Pancreatic alpha-Amylases/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing ; Mixed Function Oxygenases (EC 1.-) ; Pancreatic alpha-Amylases (EC 3.2.1.1)
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0148899
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals

Jagoda, Evelyn / Marnetto, Davide / Montinaro, Francesco / Richard, Daniel / Pagani, Luca / Capellini, Terence D

bioRxiv

Abstract: Individuals infected with the SARS-CoV-2 virus present with a wide variety of phenotypes ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via ... ...

Abstract	Individuals infected with the SARS-CoV-2 virus present with a wide variety of phenotypes ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe COVID-19 phenotype. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the severe COVID-19 phenotype. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform an locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify 4 introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. These variants likely drive the locus impact on severity by putatively modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.
Keywords	covid19
Language	English
Publishing date	2021-06-14
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.06.12.448149
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Variation in mouse pelvic morphology maps to locations enriched in Sox9 Class II and Pitx1 regulatory features.

Roseman, Charles C / Capellini, Terence D / Jagoda, Evelyn / Williams, Scott A / Grabowski, Mark / O'Connor, Christine / Polk, John D / Cheverud, James M

Journal of experimental zoology. Part B, Molecular and developmental evolution

2020 Volume 334, Issue 2, Page(s) 100–112

Abstract: Variation in pelvic morphology has a complex genetic basis and its patterning and specification is governed by conserved developmental pathways. Whether the mechanisms underlying the differentiation and specification of the pelvis also produce the ... ...

Abstract	Variation in pelvic morphology has a complex genetic basis and its patterning and specification is governed by conserved developmental pathways. Whether the mechanisms underlying the differentiation and specification of the pelvis also produce the morphological covariation on which natural selection may act, is still an open question in evolutionary developmental biology. We use high-resolution quantitative trait locus (QTL) mapping in the F
MeSH term(s)	Animals ; Biological Evolution ; Gene Expression Regulation, Developmental ; Genomics ; Genotype ; Mice ; Paired Box Transcription Factors/genetics ; Paired Box Transcription Factors/metabolism ; Pelvis/growth & development ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; SOX9 Transcription Factor/genetics ; SOX9 Transcription Factor/metabolism
Chemical Substances	Paired Box Transcription Factors ; SOX9 Transcription Factor ; Sox9 protein, mouse ; homeobox protein PITX1
Language	English
Publishing date	2020-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2103823-5
ISSN	1552-5015 ; 0022-104X ; 1552-5007
ISSN (online)	1552-5015
ISSN	0022-104X ; 1552-5007
DOI	10.1002/jez.b.22926
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Bonn / Germany

Z 2003/701: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Dietary Variation and Evolution of Gene Copy Number among Dog Breeds.

Taylor Reiter / Evelyn Jagoda / Terence D Capellini

PLoS ONE, Vol 11, Iss 2, p e

2016 Volume 0148899

Abstract	Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic α-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells.

Jagoda, Evelyn / Xue, James R / Reilly, Steven K / Dannemann, Michael / Racimo, Fernando / Huerta-Sanchez, Emilia / Sankararaman, Sriram / Kelso, Janet / Pagani, Luca / Sabeti, Pardis C / Capellini, Terence D

Molecular biology and evolution

2021 Volume 39, Issue 1

Abstract: Although some variation introgressed from Neanderthals has undergone selective sweeps, little is known about its functional significance. We used a Massively Parallel Reporter Assay (MPRA) to assay 5,353 high-frequency introgressed variants for their ... ...

Abstract	Although some variation introgressed from Neanderthals has undergone selective sweeps, little is known about its functional significance. We used a Massively Parallel Reporter Assay (MPRA) to assay 5,353 high-frequency introgressed variants for their ability to modulate the gene expression within 170 bp of endogenous sequence. We identified 2,548 variants in active putative cis-regulatory elements (CREs) and 292 expression-modulating variants (emVars). These emVars are predicted to alter the binding motifs of important immune transcription factors, are enriched for associations with neutrophil and white blood cell count, and are associated with the expression of genes that function in innate immune pathways including inflammatory response and antiviral defense. We combined the MPRA data with other data sets to identify strong candidates to be driver variants of positive selection including an emVar that may contribute to protection against severe COVID-19 response. We endogenously deleted two CREs containing expression-modulation variants linked to immune function, rs11624425 and rs80317430, identifying their primary genic targets as ELMSAN1, and PAN2 and STAT2, respectively, three genes differentially expressed during influenza infection. Overall, we present the first database of experimentally identified expression-modulating Neanderthal-introgressed alleles contributing to potential immune response in modern humans.
MeSH term(s)	Animals ; Gene Expression ; Genetic Variation ; Genome, Human ; Humans ; Immunity, Innate/genetics ; Inflammation ; Neanderthals/genetics
Language	English
Publishing date	2021-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msab304
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2137: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height.

Guo, Michael / Liu, Zun / Willen, Jessie / Shaw, Cameron P / Richard, Daniel / Jagoda, Evelyn / Doxey, Andrew C / Hirschhorn, Joel / Capellini, Terence D

eLife

2017 Volume 6

Abstract: GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g. growth plates) are difficult to study. To uncover mechanisms by which height GWAS variants ... ...

Abstract	GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g. growth plates) are difficult to study. To uncover mechanisms by which height GWAS variants function, we performed epigenetic profiling of murine femoral growth plates. The profiled open chromatin regions recapitulate known chondrocyte and skeletal biology, are enriched at height GWAS loci, particularly near differentially expressed growth plate genes, and enriched for binding motifs of transcription factors with roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at
MeSH term(s)	Animals ; Body Height ; Chondrocytes/physiology ; Chromatin/metabolism ; Epigenesis, Genetic ; Genetic Loci ; Genetic Variation ; Growth Plate/cytology ; Humans ; Mice
Chemical Substances	Chromatin
Language	English
Publishing date	2017--05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.29329
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: An encyclopedia of enhancer-gene regulatory interactions in the human genome.

Gschwind, Andreas R / Mualim, Kristy S / Karbalayghareh, Alireza / Sheth, Maya U / Dey, Kushal K / Jagoda, Evelyn / Nurtdinov, Ramil N / Xi, Wang / Tan, Anthony S / Jones, Hank / Ma, X Rosa / Yao, David / Nasser, Joseph / Avsec, Žiga / James, Benjamin T / Shamim, Muhammad S / Durand, Neva C / Rao, Suhas S P / Mahajan, Ragini /

bioRxiv : the preprint server for biology

2023

Abstract: Identifying transcriptional enhancers and their target genes is essential for understanding gene regulation and the impact of human genetic variation on ... ...

Abstract	Identifying transcriptional enhancers and their target genes is essential for understanding gene regulation and the impact of human genetic variation on disease
Language	English
Publishing date	2023-11-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.09.563812
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Inter-library loan at ZB MED