medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLCmedgen-184Research ArticleНАУЧНЫЕ ОБЗОРЫREVIEWНеоцентромерыNeocentromeresШиловаН. В.ShilovaN. V.nvsh05@mail.ruФедеральное государственное бюджетное научное учреждение «Медико-генетический научный центр»РоссияFederal State Budgetary Institution «Research Centre for Medical Genetics»Russian Federation201626012017151138Copyright © Шилова Н.В., 20172017Шилова Н.В.Shilova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/184

Центромера - фундаментальная структура, необходимая для поддержания стабильности генома. Центромерные районы хромосом характеризуются наличием альфа-сателлитной ДНК и белков центромерного комплекса, включая центромерный протеин A - CENP-A (centromere protein-A), которые, в свою очередь, определяют сборку кинетохора. Неоцентромеры - это новые, эктопические, сайты формирования функционально активного кинетохора в районах хромосом, не содержащих высокоповторенную ДНК, возникающие вследствие хромосомных перестроек. Феномен репозиции центромеры и сохранения неоцентромер в популяции является важным механизмом в видообразовании. В обзоре обсуждается значимость неоцентромер в цитогенетике целовека и эволюции хромосом.

Centromeres are essential for chromosome inheritance and genome stability. Centromeres are defined by repetitive DNA and centromeric proteins, including the centromeric histone centromere protein A (CENP-A), define the site of centromeric chromatin and kinetochore assembly. Neocentromeres are rare human chromosomal aberrations where a new centromere has formed in a previously non-centromeric location and there are new sites of assembly of functional kinetochores at ectopic loci. Evolutionary new centromeres are important steps in specification that involve centromere repositioning events that become fixed in the population. In this review the importance of neocentromeres to human health and chromosome evolution are discussed.

неоцентромерацентромерамалые сверхчисленные маркерные хромосомы (мСМХ) с неоцентромеройneocentromerecentromereneocentric small supernumerary marker chromosomesReferencesChoo K. The centromere. Oxford University Press, New York, 1997; 304 pp.Choo K. The centromere. Oxford University Press, New York, 1997; 304 pp.Рубцов НБ Хромосомы человека. Наследственные болезни: Национальное руководство. Под ред. Бочкова Н.П., Гинтера Е.К., Пузырева В.П. ГЭОТАР-Медиа. 2012. Глава 2. С. 33-68.Рубцов НБ Хромосомы человека. Наследственные болезни: Национальное руководство. Под ред. Бочкова Н.П., Гинтера Е.К., Пузырева В.П. ГЭОТАР-Медиа. 2012. Глава 2. С. 33-68.Voullaire L, Slater H, Petrovic V, Choo K. A functional marker centromere with no detectable alpha-satellite, satellite III, or CENP-B protein: Activation of a latent centromere? Am J Hum Genet. 1993; 52(6):1153-1163.Voullaire L, Slater H, Petrovic V, Choo K. A functional marker centromere with no detectable alpha-satellite, satellite III, or CENP-B protein: Activation of a latent centromere? Am J Hum Genet. 1993; 52(6):1153-1163.Amor D, Choo K. Neocentromeres: role in human disease, evolution and centromere study. Am J Hum Genet. 2002; 71(4):695-714.Amor D, Choo K. Neocentromeres: role in human disease, evolution and centromere study. Am J Hum Genet. 2002; 71(4):695-714.Cardone M, Alonso A, Pazienza M et al. Independent centromere formation in a capricious, gene-free domain of chromosome13q21 in Old World monkeys and pigs. Genome Biol. 2006; 7(10):R91.Cardone M, Alonso A, Pazienza M et al. Independent centromere formation in a capricious, gene-free domain of chromosome13q21 in Old World monkeys and pigs. Genome Biol. 2006; 7(10):R91.Olzak AM, van Essen D, Pereira AJ et al. Heterochromatin boundaries are hotspots for de novo kinetochore formation. Nature Cell Biology. 2011; 13(7):799-808.Olzak AM, van Essen D, Pereira AJ et al. Heterochromatin boundaries are hotspots for de novo kinetochore formation. Nature Cell Biology. 2011; 13(7):799-808.Craig J, Earle E, Canham P et al. Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns. Hum Mol Genet. 2003a;12(23):3109-3121.Craig J, Earle E, Canham P et al. Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns. Hum Mol Genet. 2003a;12(23):3109-3121.Alonso A, Fritz B, Hasson D et al. Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres. Genome Biol. 2007;8(7):R148.Alonso A, Fritz B, Hasson D et al. Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres. Genome Biol. 2007;8(7):R148.Alonso A, Hasson D, Cheung F, Warburton P. A paucity of heterochromatin at functional human neocentromeres. Epigenetics chromatin, 2010; 3(1):6.doi:10.1186/1756-8935-3-6.Alonso A, Hasson D, Cheung F, Warburton P. A paucity of heterochromatin at functional human neocentromeres. Epigenetics chromatin, 2010; 3(1):6.doi:10.1186/1756-8935-3-6.Steiner N, Clarke L. A novel epigenetic effect can alter centromere formation in fussion yeast. Cell. 1994;79(5):865-874.Steiner N, Clarke L. A novel epigenetic effect can alter centromere formation in fussion yeast. Cell. 1994;79(5):865-874.Maggert K, Karpen G. Acquisition and metastability of centromere identity and function: sequence analysis of a human neocentromere. Genome Res. 2000; 10:725-728.Maggert K, Karpen G. Acquisition and metastability of centromere identity and function: sequence analysis of a human neocentromere. Genome Res. 2000; 10:725-728.Black B, Bassett E. The histone variant CENP-A and centromere specification. Curr Opin Cell Biol. 2008;20(1):91-100.Black B, Bassett E. The histone variant CENP-A and centromere specification. Curr Opin Cell Biol. 2008;20(1):91-100.Van Hooser A, Ouspenski I, Gregson H et al. Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J Cell Sci. 2001;114(Pt19):3529-3542.Van Hooser A, Ouspenski I, Gregson H et al. Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J Cell Sci. 2001;114(Pt19):3529-3542.Heun P, Erhardt S, Blower M et al. Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev Cell. 2006;10(3):303-315.Heun P, Erhardt S, Blower M et al. Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev Cell. 2006;10(3):303-315.Sullivan B, Willard H.F. Stable dicentric X chromosomes with two functional centromeres. Nat Genet. 1998;20(3):227-228.Sullivan B, Willard H.F. Stable dicentric X chromosomes with two functional centromeres. Nat Genet. 1998;20(3):227-228.Nakano M, Okamoto Y, Ohzeki J, Masumoto H. Epigenetic assembly of centromeric chromatin at ectopic alpha-satellite sites on human chromosomes. J Cell Sci. 2003;116(Pt19):4021-4034.Nakano M, Okamoto Y, Ohzeki J, Masumoto H. Epigenetic assembly of centromeric chromatin at ectopic alpha-satellite sites on human chromosomes. J Cell Sci. 2003;116(Pt19):4021-4034.Craig J, Wong L, Lo A et al. Centromeric chromatin pliability and memory at a human neocentromere. EMBO J. 2003b;22(10):2495-2504.Craig J, Wong L, Lo A et al. Centromeric chromatin pliability and memory at a human neocentromere. EMBO J. 2003b;22(10):2495-2504.Wong N, Wong L, Quach J et al. Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation. PLoS Genet. 2006; 2(2):e17.Wong N, Wong L, Quach J et al. Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation. PLoS Genet. 2006; 2(2):e17.Sirvent N, Forus A, Lescaut W et al. Characterization of centromere alterations in liposarcomas. Genes Chromosomes Cancer. 2000; 29(2):117-129.Sirvent N, Forus A, Lescaut W et al. Characterization of centromere alterations in liposarcomas. Genes Chromosomes Cancer. 2000; 29(2):117-129.Italiano A, Attias R, Aurias A et al. Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C. Cancer Genet Cytogenet. 2006;167(2):122-130.Italiano A, Attias R, Aurias A et al. Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C. Cancer Genet Cytogenet. 2006;167(2):122-130.Abeliovich D, Yehuda O, Ben-Neriah S et al. dup(10q) lacking alpha-satellite DNA in bone marrow cells of a patient with acute myeloid leukemia. Cancer Genet Cytogenet. 1996;89(1):1-6.Abeliovich D, Yehuda O, Ben-Neriah S et al. dup(10q) lacking alpha-satellite DNA in bone marrow cells of a patient with acute myeloid leukemia. Cancer Genet Cytogenet. 1996;89(1):1-6.Marshall O, Chueh C, Wong L, Choo K. Neocentromeres: new insights into centromere structure, disease development and karyotype evolution. Am J Hum Genet. 2008;82(2):261-282.Marshall O, Chueh C, Wong L, Choo K. Neocentromeres: new insights into centromere structure, disease development and karyotype evolution. Am J Hum Genet. 2008;82(2):261-282.Ventura M, Mudge J, PalumboV et al. Neocentromeres in 15q24-26 map to duplicons which flanked an ancestral centromere in 15q25. Genome Res. 2003;13(9):2059-2068.Ventura M, Mudge J, PalumboV et al. Neocentromeres in 15q24-26 map to duplicons which flanked an ancestral centromere in 15q25. Genome Res. 2003;13(9):2059-2068.Voullaire L, Saffery R, Earle E et al. Mosaic inv dup(8p) marker chromosome with stable neocentromere suggests neocentromerization is a post-zygotic event. Am J Med Genet. 2001; 102(1):86-94.Voullaire L, Saffery R, Earle E et al. Mosaic inv dup(8p) marker chromosome with stable neocentromere suggests neocentromerization is a post-zygotic event. Am J Med Genet. 2001; 102(1):86-94.Gu W, Zhang F, Lupski J. Mechanisms for human genomic rearrangements. PathoGenetics. 2008 Nov 3; 1(1):4.Gu W, Zhang F, Lupski J. Mechanisms for human genomic rearrangements. PathoGenetics. 2008 Nov 3; 1(1):4.Murmann A, Conrad D, Mashek H. et al. Inverted duplication on acentric markers: mechanism of formation. Hum Mol Genet. 2009;18(12):2241-2256.Murmann A, Conrad D, Mashek H. et al. Inverted duplication on acentric markers: mechanism of formation. Hum Mol Genet. 2009;18(12):2241-2256.Chuang L, Wakui K, Sue W et al. Interstitial deletion 11(p11.12p11.2) and analphoid marker formation results in inherited Potocki-Shaffer syndrome. Am J Med Genet A. 2005;133(2):180-183.Chuang L, Wakui K, Sue W et al. Interstitial deletion 11(p11.12p11.2) and analphoid marker formation results in inherited Potocki-Shaffer syndrome. Am J Med Genet A. 2005;133(2):180-183.Knegt A, Li S, Engelen J et al. Prenatal diagnosis of a karyotypically normal pregnancy in a mother with a supernumerary neocentric 13q21 ->13q22 chromosome and balancing reciprocal deletion. Prenat Diagn. 2003;23(3):215-220.Knegt A, Li S, Engelen J et al. Prenatal diagnosis of a karyotypically normal pregnancy in a mother with a supernumerary neocentric 13q21 ->13q22 chromosome and balancing reciprocal deletion. Prenat Diagn. 2003;23(3):215-220.Dalpra L, Giardino D, Finelli P et al. Cytogenetic and molecular evaluation of 241small supernumerary marker chromosomes: Cooperative study of 19 Italian laboratories. Genet Med. 2005;7(9):620-625.Dalpra L, Giardino D, Finelli P et al. Cytogenetic and molecular evaluation of 241small supernumerary marker chromosomes: Cooperative study of 19 Italian laboratories. Genet Med. 2005;7(9):620-625.Liehr T, Weise A. Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int. J. Mol. Med. 2007; 19:719-731.Liehr T, Weise A. Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int. J. Mol. Med. 2007; 19:719-731.Liehr T. Small supernumerary marker chromosomes (sSMC). http://www.fish.uniklinikum-jena.de/sSMC.html (accessed on December 12, 2011)Liehr T. Small supernumerary marker chromosomes (sSMC). http://www.fish.uniklinikum-jena.de/sSMC.html (accessed on December 12, 2011)Klein E, Rocci M, Jvens-Raeder A et al. Five novel locations of neocentromeres in human: 18q22.1, Xq27.1~27.2, Acro p12, and heterochromatin of unknown origin. Cytogenet Genome Res. 2012;136(3):163-166.Klein E, Rocci M, Jvens-Raeder A et al. Five novel locations of neocentromeres in human: 18q22.1, Xq27.1~27.2, Acro p12, and heterochromatin of unknown origin. Cytogenet Genome Res. 2012;136(3):163-166.Liehr T, Kosyakova N, Weise A et al. First case of neocentromere formation in an otherwise normal chromosome 7. Cytogenet Genome Res. 2010;128(4):189-191.Liehr T, Kosyakova N, Weise A et al. First case of neocentromere formation in an otherwise normal chromosome 7. Cytogenet Genome Res. 2010;128(4):189-191.Warburton P. Chromosomal dynamics of human neocentromere formation. Chromosome Research. 2004;12(6):617-626.Warburton P. Chromosomal dynamics of human neocentromere formation. Chromosome Research. 2004;12(6):617-626.Warburton P, Haaf T, Gosden J et al. Characterization of a chromosome-specific chimpanzee alpha satellite subset: evolutionary relationship to subsets on human chromosomes. Genomics. 1996;33(2):220-228.Warburton P, Haaf T, Gosden J et al. Characterization of a chromosome-specific chimpanzee alpha satellite subset: evolutionary relationship to subsets on human chromosomes. Genomics. 1996;33(2):220-228.Charlesworth D, Sniegowski P, Stephan W. The evolutionary dynamics of repetitive DNA in eukaryotes. Nature. 1994;371 (6494):215-220Charlesworth D, Sniegowski P, Stephan W. The evolutionary dynamics of repetitive DNA in eukaryotes. Nature. 1994;371 (6494):215-220Rocchi M, Archidiacano N, Schempp W et al. Centromere repositioning in mammals. Heredity (Edinb). 2012;108(1):59-67.Rocchi M, Archidiacano N, Schempp W et al. Centromere repositioning in mammals. Heredity (Edinb). 2012;108(1):59-67.Capossi O, Purgato S, D’abbabbo P et al. Evolutionary descent a human neocentromere: a jump back to 17 million years ago. Genome Res. 2009;19(5):778-782.Capossi O, Purgato S, D’abbabbo P et al. Evolutionary descent a human neocentromere: a jump back to 17 million years ago. Genome Res. 2009;19(5):778-782.VenturaV, Antonacci F, Cardone MF et al. Evolutionary formation a new centromeres in macaque. Science. 2007;316(5822):243-246.VenturaV, Antonacci F, Cardone MF et al. Evolutionary formation a new centromeres in macaque. Science. 2007;316(5822):243-246.Amor D, Bentley K, Ryan J et al. Human centromere reposition “in progress”. PNAS. 2004;101(17):6542-6547.Amor D, Bentley K, Ryan J et al. Human centromere reposition “in progress”. PNAS. 2004;101(17):6542-6547.Ventura M, Weigl S, Carbone L et al. Recurrent sites for new centromere seeding. Genome Res. 2004;14(9):1696-1703.Ventura M, Weigl S, Carbone L et al. Recurrent sites for new centromere seeding. Genome Res. 2004;14(9):1696-1703.Burrack LS, Berman J. Neocentromeres and epigenetically inherited features of centromeres. Chromosome Res. 2012; 20(5):607-619.Burrack LS, Berman J. Neocentromeres and epigenetically inherited features of centromeres. Chromosome Res. 2012; 20(5):607-619.Scott KC, Sullivan BA. Neocentromeres: a place for everything and everything in its place. Trands in Genetics. 2014; 30(2):66-74/.Scott KC, Sullivan BA. Neocentromeres: a place for everything and everything in its place. Trands in Genetics. 2014; 30(2):66-74/.Saffery R, Choo K. Strategies for engineering human chromosomes with therapeutic potential. J Gene Med. 2002;4(1):5-13.Saffery R, Choo K. Strategies for engineering human chromosomes with therapeutic potential. J Gene Med. 2002;4(1):5-13.

The authors declare that there are no conflicts of interest present.