Anna A. Kashevarova
Anna A. Kashevarova, PhD, researcher in the Laboratory of Cytogenetics, Research Institute of Medical Genetics, Tomsk NRMC.Contact details
e-mail: anna.kashevarova@medgenetics.ruPhone: 8 (3822) 51-31-46
fax: 8 (3822) 51-37-44
Brief Biography
Anna A. Kashevarova graduated from the Medical Biology Faculty of the Siberian State Medical University in 2005. From 2005 to 2007 she trained in Genetics clinical residency in the Research Institute of Medical Genetics. Since 2007, she was a junior researcher, and from 2011 to the present, she works as a researcher at the Laboratory of Cytogenetics. In 2010 she defended her PhD thesis for the specialty of Genetics.
Research Interests
The main scientific studies of A.A. Kashevarova are devoted to the investigation of chromosomal imbalance and genetic variability at different stages of human development. A.A. Kashevarova is the author and co-author of more than 70 publications, including the atlas “Genome Architecture and Chromosomal Diseases. Reciprocal microdeletion and microduplication syndromes” (Tomsk, 2014).
Achievements, awards, and grants
A.A. Kashevarova was the head of several research projects supported by the Federal target programs, the Russian Foundation for Basic Research, and the Russian Science Foundation.
A.A. Kashevarova for the first time showed that in more than half of spontaneous abortions (SA) in the first trimester of pregnancy with an aneuploid karyotype abnormal cells are present in a mosaic state with a normal one. In most cases mosaicism occurs as a result of trisomy rescue. In SA the epimutations of P14ARF and RB1 cell cycle control genes were described for the first time. It has been shown that epimutations of cell cycle control genes can be one of the factors predisposing to the de novo origin of numerical chromosomal abnormalities.
In addition to numerical chromosomal anomalies, A.A. Kashevarova studies copy number variations (CNV), as a pathogenic factor for embryo development as well as one of the common causes of intellectual disability (ID) in children. The search for pathogenic CNVs associated with ID was initiated during the EU Seventh Framework Program project “Improving Diagnoses of Mental Retardation in Children in Central Eastern Europe and Central Asia through Genetic Characterisation and Bioinformatics/Statistics” (CHERISH). As a result, a molecular diagnosis was made for 9% and potentially pathogenic CNVs were detected in 22% of patients (Kashevarova et al., 2013; Kashevarova et al., 2014; Kashevarova et al., 2016). In 2014 the atlas “Genome Architecture and Chromosomal Diseases” (Kashevarova et al., 2014) was issued to meet clinical geneticists and pediatricians with novel chromosomal disorders.
Induced pluripotent stem cells (iPSCs) lines have been created from the fibroblasts with chromosomal mutations. Neurons obtained from these iPSCs can be used as an in vitro model to study the effects of mutations in their genome. A.A. Kashevarova leads the work on normalization of the karyotype of iPSCs, which could potentially form the basis of chromosomal therapy for human diseases.
Due to her scientific achievements A.A. Kashevarova was awarded with a Diploma of the Mayor of Tomsk, a Diploma of the III degree in the competition of young scientists in the framework of the IX scientific conference "Human genetics and pathology: actual problems of modern cytogenetics", a Diploma of the international scientific conference "Chromosome 2012", a Diploma for honest and active work, high scientific achievements in connection with the Day of Russian Science, a title of Laureate of the Tomsk Region Prize in the field of education, science, health, and culture in the nomination "Awards to young scientific and scientific-pedagogical employees, specialists, doctoral and postgraduate students under the age of 35 years inclusively.”
Main Publications
1. Kashevarova A.A., Lebedev I.N., Nazarenko L.P. Genome architecture and chromosomal diseases. Reciprocal microdeletion and microduplication syndromes: atlas / Ed. Acad. RAS, prof. V.P. Puzyrev - Tomsk: Publishing House "Printed Manufactory", 2014. - 56 p.2. Kashevarova AA, Skryabin NA, Nikitina TV, Lopatkina ME, Sazhenova EA, Zhigalina DI, Savchenko RR, Lebedev IN. Ontogenetic pleiotropy of genes involved in CNVs in human spontaneous abortions // Genetika. 2019. V. 55. no. 10. P. 1214-1226
3. Shnaider TA, Pristyazhnyuk IE, Menzorov AG, Matveeva NM, Nikitina TV, Khabarova AA, Skryabin NA, Kashevarova AA, Lopatkina ME, Nazarenko LP, Lebedev IN, Serov OL. Generation of four iPSC lines from two siblings with a microdeletion at the CNTN6 gene and intellectual disability // Stem Cell Res. 2019. doi: 10.1016/j.scr.2019.101591.
4. Gridina MM, Nikitina TV, Pristyazhnyuk IE, Kashevarova AA, Lopatkina ME, Vasilyev SA, Nazarenko LP, Lebedev IN, Serov OL. Generation of the induced pluripotent stem cell line, ICAGi002-A, from unaffected carrier megabase scaled duplication involving the CNTN6 gene // Stem Cell Res. 2019. https://www.sciencedirect.com/science/article/pii/S1873506119301862?via%3Dihub.
5. Khabarova A.A., Pristyazhnyuk I.E., Nikitina T.V., Gayner T.A., Torkhova N.B., Skryabin N.A., Kashevarova A.A., Babushkina N.P., Markova Zh.G., Minzhenkova M.E., Nazarenko L.P., Shilova N.V., Shorina A.R., Lebedev I.N., Serov O.L.. Induced pluripotent stem cell line, ICAGi001-A, derived from human skin fibroblasts of a patient with 2p25.3 deletion and 2p25.3-p23.3 inverted duplication // Stem Cell Res. 2019. https://doi.org/10.1016/j.scr.2018.101377.
6. Nikitina TV, Menzorov AG, Kashevarova AA, Gridina MM, Khabarova AA, Yakovleva YS, Lopatkina ME, Pristyazhnyuk IE, Vasilyev SA, Serov OL, Lebedev IN. Induced pluripotent stem cell line, IMGTi003-A, derived from skin fibroblasts of an intellectually disabled patient with ring chromosome 13 // Stem Cell Res. 2018. doi: 10.1016/j.scr.2018.11.009.
7. Kashevarova A.A., Nazarenko L.P., Skryabin N.A., Nikitina T.V., Vasilyev S.A., Tolmacheva E.N., Lopatkina M.E., Salyukova O.A., Chechetkina N.N., Vorotelyak E.A., Kalabusheva E.P., Fishman V.S., Kzhyshkowska J., Graziano C., Magini P., Romeo G., Lebedev I.N. A mosaic intragenic microduplication of LAMA1 and a constitutional 18p11.32 microduplication in a patient with keratosis pilaris and intellectual disability // Am J Med Genet A. 2018 Nov;176(11):2395-2403. doi: 10.1002/ajmg.a.40478.
8. Kashevarova A.A., Belyaeva E.O., Nikonov A.M., Plotnikova O.V., Skryabin N.A., Nikitina T.V., Vasilyev S.A., Yakovleva Y.S., Babushkina N.P., Tolmacheva E.N., Lopatkina M.E., Savchenko R.R., Nazarenko L.P., Lebedev I.N. Compound phenotype in a girl with r(22), concomitant microdeletion 22q13.32-q13.33 and mosaic monosomy 22 // Mol Cytogenet. 2018 Apr 27;11:26. doi: 10.1186/s13039-018-0375-3.
9. Gridina M.M., Matveeva N.M., Fishman V.S., Menzorov A.G., Kizilova H.A., Beregovoy N.A., Kovrigin I.I., Pristyazhnyuk I.E., Oscorbin I.P., Filipenko M.L., Kashevarova A.A., Skryabin N.A., Nikitina T.V., Sazhenova E.A., Nazarenko L.P., Lebedev I.N., Serov O.L. Allele-specific biased expression of the CNTN6 gene in iPS cell-derived neurons from a patient with intellectual disability and 3p26.3 microduplication involving the CNTN6 gene // Mol Neurobiol. 2018. V. 55 (8). P. 6533-6546. doi: 10.1007/s12035-017-0851-5.
10. Nikitina T.V., Menzorov A.G., Kashevarova A.A., Gridina M.M., Khabarova A.A., Yakovleva Y.S., Lopatkina M.E., Kizilova E.A., Vasilyev S.A., Serov O.L., Lebedev I.N. Generation of two iPSC lines (IMGTi001-A and IMGTi001-B) from human skin fibroblasts with ring chromosome 22 // Stem Cell Res. 2018 Aug;31:244-248. doi: 10.1016/j.scr.2018.08.012.
11. Lebedev I.N., Nazarenko L.P., Skrayabin N.A., Babushkina N.P., Kashevarova A.A. A de novo microtriplication at 4q21.21-q21.22 in a patient with a vascular malignant hemangioma, elongated sigmoid colon, development delay, and absence of speech // American Journal of Medical Genetics. Part A. 2016. V. 170A. № 8. P. 2089-2096. DOI: 10.1002/ajmg.a.37754
12. Nikitina T.V., Sazhenova E.A., Tolmacheva E.N., Sukhanova N.N., Kashevarova A.A., Skryabin N.A., Vasilyev S.A., Nemtseva T.N., Yuriev S.Y., Lebedev I.N. Comparative cytogenetic analysis of spontaneous abortions in recurrent and sporadic pregnancy losses // Biomedicine Hub. 2016. 1:446099. DOI: 10.1159/000446099
13. Kashevarova A.A., Nazarenko L.P., Schultz-Pedersen S., Skryabin N.A., Salyukova O.A., Chechetkina N.N., Tolmacheva E.N., Rudko A.A., Magini P., Graziano C., Romeo G., Joss Sh., Tümer Z., Lebedev I.N. Single gene microdeletions and microduplication of 3p26.3 in three unrelated families: CNTN6 as a new candidate gene for intellectual disability // Molecular Cytogenetics. 2014. 7:97. DOI: 10.1186/s13039-014-0097-0
14. Kashevarova A.A., Nazarenko L.P., Skryabin N.A., Salyukova O.A., Chechetkina N.N., Tolmacheva E.N., Sazhenova E.A., Magini P., Graziano C., Romeo G., Kučinskas V., Lebedev I.N. Array CGH analysis of a cohort of Russian patients with intellectual disability // Gene. 2014. V. 536. № 1. P. 145-150. DOI: 10.1016/j.gene.2013.11.029
15. Rowsey R., Kashevarova A., Murdoch B., Dickenson C., Woodruff T., Cheng E., Hunt P., Hassold T. Germline mosaicism does not explain the maternal age effect on trisomy // American Journal of Medical Genetics. 2013. V. 161A. № 10. P. 2495-2503. DOI: 10.1002/ajmg.a.36120
16. Kashevarova A.A., Lebedev I.N. Genomic Architecture of Human Chromosomal Diseases // Genetika. 2016. V. 52. № 5. P. 447-462.
17. Lopatkina M.E., Kashevarova A.A., Lebedev I.N. Estimation of association of CNTN6 copy number variation with idiopathic intellectual disability // Genetika. 2016. V. 52. № 9. P. 1004-1006
18. Kashevarova A.A., Skryabin N.A., Cheremnykh A.D., Tolmacheva E.N., Sazhenova E.A., Salyukova O.A., Chechetkina N.N., Didenko L.I., Sukhanova N.N., Yakovleva Yu.S., Torkhova N.B., Nazarenko L.P., Magini P., Graziano C., Romeo G., Lebedev I.N. Clinical and genetic analysis of idiopathic intellectual disability based on array comparative genomic hybridization // Zh Nevrol Psikhiatr Im S S Korsakova. 2013. V. 113. № 9. P. 70-74.
19. Tolmacheva E.N., Kashevarova A.A., Skriabin N.A., Lebedev I.N. Epigenetic effects of trisomy 16 in the human placenta // Mol Biol (Mosk). 2013. V. 47. № 3. P. 423-432.
20. Tolmacheva E.N., Kashevarova A.A., Skriabin N.A., Lebedev I.N. DNA methylation profile in human placental tissues // Mol Biol (Mosk). 2011. V. 45. № 3. P. 538-545.
21. Kashevarova A.A., Tolmacheva E.N., Sazhenova E.A., Sukhanova N.N., Lebedev I.N. Methylation profiling of the cell cycle regulating genes in placenta of human embryos with chromosomal mosaicism // Mol Biol (Mosk). 2011. V. 45. № 2. P. 316-324.