Cell junction protein armadillo repeat gene deleted in velo-cardio-facial syndrome is expressed in the skin and colocalizes with autoantibodies of patients affected by a new variant of endemic pemphigus foliaceus in Colombia

Velez, Ana Maria Abreu; Yi, Hong; Howard, Michael S.

doi:10.5826/dpc.0704a02

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…The association between pulse pressure and immune cell- eQTLs was also an unexpected observation. Multiple immune cell- eGenes that colocalized with pulse pressure are involved in immune response and inflammation, including ASAP2 , SH3YL1 , ARVCF, and ATP1B1 60 – 63 , and changes in their expression may affect the mechanisms that trigger the inflammatory response and its effects on blood pressure. To validate enrichments of the spatiotemporal eQTLs and GWAS signals, we determined the tissue context of each eQTL signal using an independent method, multi-variate adaptive shrinkage (mash) 64 , and observed very similar enrichments (see Supplementary Note 2, Supplementary Figs.…”

Section: Resultsmentioning

confidence: 99%

Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease

et al. 2023

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The causal variants and genes underlying thousands of cardiac GWAS signals have yet to be identified. Here, we leverage spatiotemporal information on 966 RNA-seq cardiac samples and perform an expression quantitative trait locus (eQTL) analysis detecting eQTLs considering both eGenes and eIsoforms. We identify 2,578 eQTLs associated with a specific developmental stage-, tissue- and/or cell type. Colocalization between eQTL and GWAS signals of five cardiac traits identified variants with high posterior probabilities for being causal in 210 GWAS loci. Pulse pressure GWAS loci are enriched for colocalization with fetal- and smooth muscle- eQTLs; pulse rate with adult- and cardiac muscle- eQTLs; and atrial fibrillation with cardiac muscle- eQTLs. Fine mapping identifies 79 credible sets with five or fewer SNPs, of which 15 were associated with spatiotemporal eQTLs. Our study shows that many cardiac GWAS variants impact traits and disease in a developmental stage-, tissue- and/or cell type-specific fashion.

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Section: Resultsmentioning

confidence: 99%

Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease

et al. 2023

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“…The association between pulse pressure and immune cell-eQTLs was also an unexpected observation. Multiple immune cell-eGenes that colocalized with pulse pressure are involved in immune response and inflammation, including ASAP2, SH3YL1, ARVCF and ATP1B1 [55][56][57][58] , and changes in their expression may affect the mechanisms that trigger the inflammatory response and its effects on blood pressure. In summary, by integrating context-associated eQTLs with GWAS, we were able to find that the SNPs associated with three of the five cardiac traits are enriched for being functional in specific spatiotemporal contexts, including associations between pulse pressure and fetal-like iPSC-CVPC-eQTLs and between pulse rate and adult-eQTLs.…”

Section: Cardiac Traits Enriched For Eqtls That Function In Specific ...mentioning

confidence: 99%

Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease

D’Antonio

Arthur

Nguyen

et al. 2021

Preprint

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The causal variants and genes underlying thousands of cardiac GWAS signals have yet to be identified. To address this issue, we leveraged spatiotemporal information on 966 RNA-seq cardiac samples and performed an expression quantitative trait locus (eQTL) analysis detecting ~26,000 eQTL signals associated with more than 11,000 eGenes and 7,000 eIsoforms. Approximately 2,500 eQTLs were associated with specific cardiac stages, organs, tissues and/or cell types. Colocalization and fine mapping of eQTL and GWAS signals of five cardiac traits in the UK BioBank identified variants with high posterior probabilities for being causal in 210 GWAS loci. Over 50 of these loci represent novel functionally annotated cardiac GWAS signals. Our study provides a comprehensive resource mapping regulatory variants that function in spatiotemporal context-specific manners to regulate cardiac gene expression, which can be used to functionally annotate genomic loci associated with cardiac traits and disease.

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New complex cell junctions in and around the intervertebral discs discovered using autoantibodies from patients affected by endemic pemphigus foliaceus in El Bagre, Colombia, South America

Abreu Velez,

Hashimoto,

Arango

et al. 2024

Int J Dermatology

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BackgroundTraditionally, the intervertebral disks' (IVD) nucleus pulposus (NP) and annulus fibrosus (AF) are considered to have few cellular components and cell junctions. Patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, experience back pain in the spinal areas of the lower and upper back. Here, we investigate the reactivity of the patient's autoantibodies to structures in and around the IVDs at the cellular level.MethodsWe first administered a questionnaire and performed a medical examination. We then tested for autoreactivity against IVDs by indirect immunofluorescence, confocal microscopy, and reflectance confocal microscopy using bovine and human tissues as antigen sources. We tested 45 sera from patients affected by the disease and 45 control sera from the endemic area matched by age, gender, demographics, and work activity.ResultsMost of the patient sera revealed polyclonal antibodies against newly discovered cell junctions in the NP and AF, including their translamellar cross‐bridges. Additional reactivities were detected against cell junctions in the spinal cord neurons, paraspinal nerves, blood vessels, anterior and posterior longitudinal ligaments, and paraspinal skeletal muscles. The reactivities of the patient's autoantibodies co‐localized with those of commercially available antibodies to desmoplakins I–II, armadillo repeat gene deleted in velo‐cardio‐facial syndrome, plakophilin‐4, and myocardium‐enriched zonula occludens‐1‐associated protein (p < 0.001).ConclusionsWe discovered novel complex cell junctions in the IVDs using patients' autoantibodies. These discoveries open a new chapter in the knowledge of IVD, representing a breakthrough pertinent to many diseases.

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Cell junction protein armadillo repeat gene deleted in velo-cardio-facial syndrome is expressed in the skin and colocalizes with autoantibodies of patients affected by a new variant of endemic pemphigus foliaceus in Colombia

Cited by 3 publications

References 14 publications

Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease

Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease

Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease

New complex cell junctions in and around the intervertebral discs discovered using autoantibodies from patients affected by endemic pemphigus foliaceus in El Bagre, Colombia, South America

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