Somatic mosaicism and structural variability of GBP3 gene in atherosclerosis
https://doi.org/10.15372/ATER20190404
Abstract
The goal of the study was to analyze copy number variation (CNV) in the GBP3 gene between white blood cells and atherosclerotic plaques of patients with carotid atherosclerosis. The material was both blood samples and atherosclerotic plaques obtained from the same patients with carotid atherosclerosis (n = 94). Assessment of CNV was performed using digital droplet PCR. As a result, it was shown that among 94 patients with carotid atherosclerosis, the CNV frequency was 44 % in the GBP3 gene in leukocytes. Deletion was detected in 5 (5.3 %) patients, and loss in 36 (38.3 %) patients. The gain was identified in one patient. Somatic mosaicism was found in 12 (13 %) of patients, comparing DNA samples of atherosclerotic plaque tissue and white blood cells from the same patients. Mosaic copy number losses predominantly were detected in white blood cells, in contrast mosaic copy number gains were identified in atherosclerotic plaques. Somatic mosaicism of the GBP3 gene is widespread in atherosclerosis. Different ratio of mosaic clones carrying certain type of CNV in GBP3 gene is presented.
About the Authors
A. A. Sleptsov
1. Shia W.-C., Ku T.H., Tsao Y.M. et al. Genetic copy number variants in myocardial infarction patients with hyperlipidemia // BMC Genomics. 2011. Vol. 12, Suppl 3. P. S23.
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3. Boon-Peng H., Mat Jusoh J.A., Marshall C.R. et al. Rare copy number variants identified suggest the regulating pathways in hypertension-related left ventricular hypertrophy // PLoS One. 2016. Vol. 11, N 3. P. e0148755.
4. Glessner J.T. et al. CNV association of diverse clinical phenotypes from eMERGE reveals novel disease biology underlying cardiovascular disease // Int. J. Cardiol. 2019. doi: DOI10.1016/j.ijcard.2019.07.058
5. Nazarenko M.S., Sleptcov A.A., Lebedev I.N. et al. Genomic structural variations for cardiovascular and metabolic comorbidity // Sci. Rep. 2017. Vol. 7. P. 41268.
6. Tretina K., Park E.S., Maminska A., MacMicking J.D. Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease // J. Exp. Med. 2019. Vol. 216, N 3. P. 482–500.
7. Xie G., Myint P.K., Voora D. et al. Genome-wide association study on progression of carotid artery intima media thickness over 10 years in a Chinese cohort // Atherosclerosis. 2015. Vol. 243, N 1. P. 30–37.
8. Goo Y.-H., Son S.H., Yechoor V.K., Paul A. Transcriptional profiling of foam cells reveals induction of guanylate-binding proteins following Western diet acceleration of atherosclerosis in the absence of global changes in inflammation // J. Am. Heart Assoc. Vol. 5, N 4. P. e002663.
9. Forsberg L.A., Gisselsson D., Dumanski J.P. Mosaicism in health and disease clones picking up speed // Nat. Rev. Genet. 2017. Vol. 18, N 2. P. 128–142.
10. Sambrook J., Russell D.W. Molecular cloning. A laboratory manual. 3 vol. N.Y.: Cold Spring Harbor, 2001.
11. Zhou B., Haney M.S., Zhu X. et al. Detection and quantification of mosaic genomic DNA variation in primary somatic tissues using ddPCR: Analysis of mosaic transposable-element insertions, copy-number variants, and single-nucleotide variants // Methods Mol. Biol. 2018. Vol. 1768. P. 173–190.
12. Fujiki K., Shirahige K., Kaur M. et al. Mosaic ratio quantification of isochromosome 12p in PallisterKillian syndrome using droplet digital PCR // Mol. Genet. Genomic Med. 2016. Vol. 4, N 3. P. 257–261.
13. Mills R.E., Walter K., Stewart C. et al. Mapping copy number variation by population-scale genome sequencing // Nature. 2011. Vol. 470, N 7332. P. 59–65.
14. Park H., Kim J.I., Ju Y.S. et al. Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing // Nat. Genet. 2010. Vol. 42, N 5. P. 400–405.
15. Steensma D.P., Bejar R., Jaiswal S. et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes // Blood. 2015. Vol. 126, N 1. P. 9–16.
Russian Federation
Russian Federation
634050, Tomsk, Naberezhnaya reki Ushayky, 10
M. S. Nazarenko
Research Institute of Medical Genetics of Tomsk National Research Medical Center of RAS;
Siberian State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
634050, Tomsk, Naberezhnaya reki Ushayky, 10;
634050, Tomsk, Moskovsky path, 2
A. V. Zaitseva
Siberian State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
634050, Tomsk, Moskovsky path, 2
A. N. Kazantsev
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation
Russian Federation
650002, Kemerovo, Sosnovy blvd., 6
N. N. Burkov
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation
Russian Federation
650002, Kemerovo, Sosnovy blvd., 6
O. L. Barbarash
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation
Russian Federation
650002, Kemerovo, Sosnovy blvd., 6
V. P. Puzyrev
Research Institute of Medical Genetics of Tomsk National Research Medical Center of RAS;
Siberian State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
634050, Tomsk, Naberezhnaya reki Ushayky, 10;
634050, Tomsk, Moskovsky path, 2
References
1. Shia W.-C., Ku T.H., Tsao Y.M. et al. Genetic copy number variants in myocardial infarction patients with hyperlipidemia // BMC Genomics. 2011. Vol. 12, Suppl 3. P. S23.
2. Marques F.Z., Prestes P.R., Pinheiro L.B. et al. Measurement of absolute copy number variation reveals association with essential hypertension // BMC Med. Genomics. 2014. Vol. 7. P. 44.
3. Boon-Peng H., Mat Jusoh J.A., Marshall C.R. et al. Rare copy number variants identified suggest the regulating pathways in hypertension-related left ventricular hypertrophy // PLoS One. 2016. Vol. 11, N 3. P. e0148755.
4. Glessner J.T. et al. CNV association of diverse clinical phenotypes from eMERGE reveals novel disease biology underlying cardiovascular disease // Int. J. Cardiol. 2019. doi: DOI10.1016/j.ijcard.2019.07.058
5. Nazarenko M.S., Sleptcov A.A., Lebedev I.N. et al. Genomic structural variations for cardiovascular and metabolic comorbidity // Sci. Rep. 2017. Vol. 7. P. 41268.
6. Tretina K., Park E.S., Maminska A., MacMicking J.D. Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease // J. Exp. Med. 2019. Vol. 216, N 3. P. 482–500.
7. Xie G., Myint P.K., Voora D. et al. Genome-wide association study on progression of carotid artery intima media thickness over 10 years in a Chinese cohort // Atherosclerosis. 2015. Vol. 243, N 1. P. 30–37.
8. Goo Y.-H., Son S.H., Yechoor V.K., Paul A. Transcriptional profiling of foam cells reveals induction of guanylate-binding proteins following Western diet acceleration of atherosclerosis in the absence of global changes in inflammation // J. Am. Heart Assoc. Vol. 5, N 4. P. e002663.
9. Forsberg L.A., Gisselsson D., Dumanski J.P. Mosaicism in health and disease clones picking up speed // Nat. Rev. Genet. 2017. Vol. 18, N 2. P. 128–142.
10. Sambrook J., Russell D.W. Molecular cloning. A laboratory manual. 3 vol. N.Y.: Cold Spring Harbor, 2001.
11. Zhou B., Haney M.S., Zhu X. et al. Detection and quantification of mosaic genomic DNA variation in primary somatic tissues using ddPCR: Analysis of mosaic transposable-element insertions, copy-number variants, and single-nucleotide variants // Methods Mol. Biol. 2018. Vol. 1768. P. 173–190.
12. Fujiki K., Shirahige K., Kaur M. et al. Mosaic ratio quantification of isochromosome 12p in PallisterKillian syndrome using droplet digital PCR // Mol. Genet. Genomic Med. 2016. Vol. 4, N 3. P. 257–261.
13. Mills R.E., Walter K., Stewart C. et al. Mapping copy number variation by population-scale genome sequencing // Nature. 2011. Vol. 470, N 7332. P. 59–65.
14. Park H., Kim J.I., Ju Y.S. et al. Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing // Nat. Genet. 2010. Vol. 42, N 5. P. 400–405.
15. Steensma D.P., Bejar R., Jaiswal S. et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes // Blood. 2015. Vol. 126, N 1. P. 9–16.
Review
For citations:
Sleptsov A.A., Nazarenko M.S., Zaitseva A.V., Kazantsev A.N., Burkov N.N., Barbarash O.L., Puzyrev V.P. Somatic mosaicism and structural variability of GBP3 gene in atherosclerosis. Ateroscleroz. 2019;15(4):46-51. (In Russ.) https://doi.org/10.15372/ATER20190404
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