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 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 Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

2017 ◽  
Vol 20 (4) ◽  
pp. 267-270 ◽  
Author(s):  
Hamdi Mbarek ◽  
Yuri Milaneschi ◽  
Jouke-Jan Hottenga ◽  
Lannie Ligthart ◽  
Eco J. C. de Geus ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Genome Wide Association Study ◽  
Major Depressive ◽  
Significance Level ◽  
Functional Studies ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10−8) and gene-based (p = 1.48 × 10−7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

scholarly journals The FAM171A2 gene is a key regulator of progranulin expression and modifies the risk of multiple neurodegenerative diseases

2020 ◽  
Vol 6 (43) ◽  
pp. eabb3063
Author(s):  
Wei Xu ◽  
Si-Da Han ◽  
Can Zhang ◽  
Jie-Qiong Li ◽  
Yan-Jiang Wang ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Genome Wide Association Study ◽  
In Vitro Study ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Pathophysiological Role ◽  
Independent Cohort

Progranulin (PGRN) is a secreted pleiotropic glycoprotein associated with the development of common neurodegenerative diseases. Understanding the pathophysiological role of PGRN may help uncover biological underpinnings. We performed a genome-wide association study to determine the genetic regulators of cerebrospinal fluid (CSF) PGRN levels. Common variants in region of FAM171A2 were associated with lower CSF PGRN levels (rs708384, P = 3.95 × 10−12). This was replicated in another independent cohort. The rs708384 was associated with increased risk of Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia and could modify the expression of the FAM171A2 gene. FAM171A2 was considerably expressed in the vascular endothelium and microglia, which are rich in PGRN. The in vitro study further confirmed that the rs708384 mutation up-regulated the expression of FAM171A2, which caused a decrease in the PGRN level. Collectively, genetic, molecular, and bioinformatic findings suggested that FAM171A2 is a key player in regulating PGRN production.

scholarly journals ESR1, WT1, WNT4, ATM and TERT loci are major contributors to uterine leiomyoma predisposition

2018 ◽  
Author(s):  
Niko Välimäki ◽  
Heli Kuisma ◽  
Annukka Pasanen ◽  
Oskari Heikinheimo ◽  
Jari Sjöberg ◽  
...  
Keyword(s):  
Estrogen Receptor Alpha ◽  
Genome Wide Association Study ◽  
Benign Tumors ◽  
Risk Alleles ◽  
Estrogen Exposure ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Level ◽  
Genomic Risk

ABSTRACTUterine leiomyomas (ULs) are benign tumors that are a major burden to women’s health. A genome-wide association study on 5,417 UL cases and 331,791 controls was performed, followed by replication of the genomic risk in two cohorts. Effects of the identified risk alleles were evaluated in view of molecular and clinical features.Five loci displayed a genome-wide significant association; the previously reported TNRC6B, and four novel loci ESR1 (ERα), WT1, WNT4, and ATM. The sixth hit TERT is also a conceivable target. The combined polygenic risk contributed by these loci was associated with MED12 mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis. While the fundamental role of sex hormones in UL aetiology has been clear, this work reveals a connection to estrogen receptor alpha on genetic level and suggests that determinants of UL growth associated with estrogen exposure have an inherited component.

scholarly journals Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
E. A. Hisey ◽  
H. Hermans ◽  
Z. T. Lounsberry ◽  
F. Avila ◽  
R. A. Grahn ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Wide Association Study ◽  
Secondary Infection ◽  
Whole Genome Sequencing Data ◽  
Incomplete Penetrance ◽  
Whole Genome ◽  
Genome Wide ◽  
A Genome

Abstract Background Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait. Results A genome wide association study (GWAS) was performed using the Axiom 670 k Equine Genotyping array (MNEc670k) utilizing 14 cases and 38 controls phenotyped for distichiasis. An additive single locus mixed linear model (EMMAX) approach identified a 1.83 Mb locus on ECA5 and a 1.34 Mb locus on ECA13 that reached genome-wide significance (pcorrected = 0.016 and 0.032, respectively). Only the locus on ECA13 withstood replication testing (p = 1.6 × 10− 5, cases: n = 5 and controls: n = 37). A 371 kb run of homozygosity (ROH) on ECA13 was found in 13 of the 14 cases, providing evidence for a recessive mode of inheritance. Haplotype analysis (hapQTL) narrowed the region of association on ECA13 to 163 kb. Whole-genome sequencing data from 3 cases and 2 controls identified a 16 kb deletion within the ECA13 associated haplotype (ECA13:g.178714_195130del). Functional annotation data supports a tissue-specific regulatory role of this locus. This deletion was associated with distichiasis, as 18 of the 19 cases were homozygous (p = 4.8 × 10− 13). Genotyping the deletion in 955 horses from 54 different breeds identified the deletion in only 11 non-Friesians, all of which were carriers, suggesting that this could be causal for this Friesian disorder. Conclusions This study identified a 16 kb deletion on ECA13 in an intergenic region that was associated with distichiasis in Friesian horses. Further functional analysis in relevant tissues from cases and controls will help to clarify the precise role of this deletion in normal and abnormal eyelash development and investigate the hypothesis of incomplete penetrance.

scholarly journals Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gita A. Pathak ◽  
Kritika Singh ◽  
Tyne W. Miller-Fleming ◽  
Frank R. Wendt ◽  
Nava Ehsan ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Clinical Symptoms ◽  
Ethnic Studies ◽  
Host Genetics ◽  
Protein Levels ◽  
Genome Wide ◽  
A Genome ◽  
Causal Genes ◽  
Host Inflammatory Response

AbstractDespite rapid progress in characterizing the role of host genetics in SARS-Cov-2 infection, there is limited understanding of genes and pathways that contribute to COVID-19. Here, we integrate a genome-wide association study of COVID-19 hospitalization (7,885 cases and 961,804 controls from COVID-19 Host Genetics Initiative) with mRNA expression, splicing, and protein levels (n = 18,502). We identify 27 genes related to inflammation and coagulation pathways whose genetically predicted expression was associated with COVID-19 hospitalization. We functionally characterize the 27 genes using phenome- and laboratory-wide association scans in Vanderbilt Biobank (n = 85,460) and identified coagulation-related clinical symptoms, immunologic, and blood-cell-related biomarkers. We replicate these findings across trans-ethnic studies and observed consistent effects in individuals of diverse ancestral backgrounds in Vanderbilt Biobank, pan-UK Biobank, and Biobank Japan. Our study highlights and reconfirms putative causal genes impacting COVID-19 severity and symptomology through the host inflammatory response.

scholarly journals Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study

PLoS Genetics ◽  
2020 ◽  
Vol 16 (10) ◽  
pp. e1009065
Author(s):  
Marco Galardini ◽  
Olivier Clermont ◽  
Alexandra Baron ◽  
Bede Busby ◽  
Sara Dion ◽  
...  
Keyword(s):  
Association Study ◽  
Iron Uptake ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Identification of genetic factors influencing metabolic dysregulation and retinal support for MacTel, a retinal disorder

2020 ◽  
Author(s):  
Roberto Bonelli ◽  
Victoria E Jackson ◽  
Aravind Prasad ◽  
Jacob E Munro ◽  
Samaneh Farashi ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Retinal Disease ◽  
Causative Role ◽  
Macular Telangiectasia ◽  
Metabolic Dysregulation ◽  
Genome Wide ◽  
A Genome ◽  
Risk Scoring ◽  
Macular Telangiectasia Type 2

Macular Telangiectasia Type 2 (MacTel) is a rare degenerative retinal disease with complex genetic architecture. We performed a genome-wide association study on 1,067 MacTel patients and 3,799 controls, which identified eight novel genome-wide significant loci (p<5E-8), and confirmed all three previously reported loci. Using MAGMA, eQTL and transcriptome-wide association analysis, we prioritised 48 genes implicated in serine-glycine biosynthesis, metabolite transport, and retinal vasculature and thickness. Mendelian randomization indicated a likely causative role of serine (FDR=3.9E-47) and glycine depletion (FDR=0.006) as well as alanine abundance (FDR=0.009). Polygenic risk scoring achieved an accuracy of 0.74 and was associated in UKBiobank with retinal damage (p=0.009). This represents the largest genetic study on MacTel to date, and further highlights genetically-induced systemic and tissue-specific metabolic dysregulation in MacTel patients, which impinges on retinal health.

scholarly journals Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries

2021 ◽  
Author(s):  
Doris Skoric-Milosavljevic ◽  
Rafik Tadros ◽  
Fernanda M Bosada ◽  
Federico Tessadori ◽  
Jan Hendrik van Weerd ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Regulatory Element ◽  
Susceptibility Locus ◽  
Mouse Heart ◽  
Polygenic Risk Score ◽  
Polygenic Inheritance ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome

Background: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Methods: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). Results: SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.

scholarly journals Defining the genetic control of human blood plasma N-glycome using genome-wide association study

2018 ◽  
Author(s):  
Sodbo Zh. Sharapov ◽  
Yakov A. Tsepilov ◽  
Lucija Klaric ◽  
Massimo Mangino ◽  
Gaurav Thareja ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Association Study ◽  
Genetic Control ◽  
Human Blood ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Human Blood Plasma ◽  
Genome Wide ◽  
A Genome

AbstractGlycosylation is a common post-translational modification of proteins. It is known, that glycans are directly involved in the pathophysiology of every major disease. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here, we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people. We discovered and replicated twelve loci. This allowed us to demonstrate a clear overlap in genetic control between total plasma and IgG glycosylation. Majority of loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3, and MGAT5). We, however, also found loci that are likely to reflect other, more complex, aspects of plasma glycosylation process. Functional genomic annotation suggested the role of DERL3, which potentially highlights the role of glycoprotein degradation pathway, and such transcription factor as IKZF1.

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