COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay

Marom, Ronit; Burrage, Lindsay C.; Venditti, Rossella; Clément, Aurélie; Blanco-Sánchez, Bernardo; Jain, Mahim; Scott, Daryl A.; Rosenfeld, Jill A.; Sutton, V. Reid; Shinawi, Marwan; Mirzaa, Ghayda; DeVile, Catherine; Roberts, Rowenna; Calder, Alistair; Allgrove, Jeremy; Grafe, Ingo; Lanza, Denise G.; Li, Xiaohui; Joeng, Kyu Sang; Lee, Yi-Chien; Song, I-Wen; Sliepka, Joseph M.; Batkovskyte, Dominyka; Washington, Megan; Dawson, Brian; Jin, Zixue; Jiang, Mingming; Chen, Shan; Chen, Yuqing; Tran, Alyssa A.; Emrick, Lisa; Murdock, David R.; Hanchard, Neil A.; Zapata, Gladys; Mehta, Nitesh R; Weis, Mary Ann; Scott, Abbey; Tremp, Brenna A.; Phillips, Jennifer B.; Wegner, Jeremy; Taylor-Miller, Tashunka; Gibbs, Richard A.; Jhangiani, Shalini N.; Hicks, John; Stottmann, Rolf W.; Dickinson, Mary E.; Seavitt, John R.; Heaney, Jason D.; Eyre, David W; Westerfield, Monte; Matteis, Maria Antonietta De; Lee, Brendan

doi:10.1016/j.ajhg.2021.08.002

Cited by 25 publications

(22 citation statements)

References 62 publications

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“…Copb2 forms part of a protein complex involved in retrograde vesicle budding from the Golgi apparatus and secretion of macromolecule cargo, such as collagen, which is critical for bone and connective tissue development. Mice and fish developing with deficits in copb2 have delayed bone mineralization and low bone density, as well as defects in type II collagen trafficking and secretion ( 78 ). Zebrafish mutants of copb2 develop mispatterned, kinked notochords with a disorganized perinotochordal basement membrane, which is secreted by notochord sheath cells ( 79 ).…”

Section: Discussionmentioning

confidence: 99%

Leafy and weedy seadragon genomes connect genic and repetitive DNA features to the extravagant biology of syngnathid fishes

Small

Healey

Currey

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Seadragons are a remarkable lineage of teleost fishes in the family Syngnathidae, renowned for having evolved male pregnancy. Comprising three known species, seadragons are widely recognized and admired for their fantastical body forms and coloration, and their specific habitat requirements have made them flagship representatives for marine conservation and natural history interests. Until recently, a gap has been the lack of significant genomic resources for seadragons. We have produced gene-annotated, chromosome-scale genome models for the leafy and weedy seadragon to advance investigations of evolutionary innovation and elaboration of morphological traits in seadragons as well as their pipefish and seahorse relatives. We identified several interesting features specific to seadragon genomes, including divergent noncoding regions near a developmental gene important for integumentary outgrowth, a high genome-wide density of repetitive DNA, and recent expansions of transposable elements and a vesicular trafficking gene family. Surprisingly, comparative analyses leveraging the seadragon genomes and additional syngnathid and outgroup genomes revealed striking, syngnathid-specific losses in the family of fibroblast growth factors (FGFs), which likely involve reorganization of highly conserved gene regulatory networks in ways that have not previously been documented in natural populations. The resources presented here serve as important tools for future evolutionary studies of developmental processes in syngnathids and hold value for conservation of the extravagant seadragons and their relatives.

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Section: Discussionmentioning

confidence: 99%

Leafy and weedy seadragon genomes connect genic and repetitive DNA features to the extravagant biology of syngnathid fishes

Small

Healey

Currey

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…11 Recently, heterozygous COPB2 loss-of-function variants have been associated with developmental delay and osteoporosis. 12 Therefore, the clinical consequences of ARCN1, COPA, and COPB2 variants are distinctively different, despite all encoding components of COPI. These observations raise the possibility that these COPI subunits have noncanonical functions outside of COPI.…”

Section: Disease-causing Variant Spectrum Of Arcn1mentioning

confidence: 99%

Expanding the phenotypic spectrum of ARCN1-related syndrome

Ritter

Gold

Hayashi

et al. 2022

Genetics in Medicine

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“…We identified differential expression of proteins between the HCT and PMF cells, and 2,916 and 2,816 proteins were differentially expressed in HCT and PMF cells, respectively. Notably, the expression of coatomer complex subunit beta 2(COPB2), an essential protein required for Golgi budding and vesicular trafficking [ 33 ], was decreased in both HCT-BR and PMF-BR cells, compared with that in the corresponding PT cells. A pie chart showing the biological process annotations of the proteins in each cell type is shown in Figure 10 .…”

Section: Resultsmentioning

confidence: 99%

Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells

Nittayaboon

Leetanaporn

Sangkhathat

et al. 2022

BioMed Research International

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Colorectal cancer (CRC) is the third most common cancer worldwide. The gut microbiota plays a critical role in homeostasis and carcinogenesis. Butyrate, a short-chain fatty acid produced by the gut microbiota, plays a role in intestinal homeostasis and acts as an anticancer agent by inhibiting growth and inducing apoptosis. However, microbiota studies have revealed an abnormally high abundance of butyrate-producing bacteria in patients with CRC and indicated that it leads to chemoresistance. We characterized butyrate resistance in HCT-116 and PMF-K014 CRC cells after treatment with a maximum butyrate concentration of 3.2 mM. The 50% inhibitory concentration of butyrate was increased in butyrate-resistant (BR) cells compared with that in parental (PT) cells. The mechanism of butyrate resistance was initially investigated by determining the expression of butyrate influx- and drug efflux-related genes. We found the increased expression of influx- and efflux-related genes in BR cells compared with that in PT cells. Proteomic data showed both identical and different proteins in PT and BR cells. Further analysis revealed the crossresistance of HCT-116 cells to metformin and oxaliplatin and that of PMF-K014 cells to 5-fluorouracil. Our findings suggest that the acquisition of butyrate resistance induces the development of chemoresistance in CRC cells, which may play an important role in CRC development, treatment, and metastasis.

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COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay

Cited by 25 publications

References 62 publications

Leafy and weedy seadragon genomes connect genic and repetitive DNA features to the extravagant biology of syngnathid fishes

Leafy and weedy seadragon genomes connect genic and repetitive DNA features to the extravagant biology of syngnathid fishes

Expanding the phenotypic spectrum of ARCN1-related syndrome

Characterization of Butyrate-Resistant Colorectal Cancer Cell Lines and the Cytotoxicity of Anticancer Drugs against These Cells

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