From Big Medical Encyclopedia

CYTOGENETICS (Greek kytos a receptacle, here — a cell + geneti-kos relating to an origin) — the section of genetics devoted to studying of cellular bases of heredity and variability of organisms.

Material units of heredity of eukaryotic organisms — molecules DNA (see. Deoxyribonucleic acid) is localized preferential in structures of a cellular kernel — chromosomes (see). Therefore C. studies a structure and functioning of chromosomes during the ensuring process of inheritance with them (see N the expert of le to a grub nnost) and changes of properties and signs (see Variability). Cellular patterns of heredity, uniform for all types of eukaryotic organisms, also the cytogenetics of plants, cytogenetics of animals make the general Ts. Sushchestvuyet's keeping, since the end of the 50th of 20 century the cytogenetics of the person intensively develops. The general C. it can be also subdivided on the studied level (microscopic, submicroscopic, molecular) the organizations of hereditary structures.

C. as the science arose at the end of

19 — the beginning of 20 century on the knowledge base about patterns of inheritance of characters during the crossings of organisms and about morphology and behavior in cellular divisions of the main nuclear structures — chromosomes. From 60th

20 century process of association classical began C. and molecular genetics (see) therefore appeared molecular C.

History C. conditionally is divided into three periods. First period (end

of 19 century and the first two decades 20 century) includes origin and justification of the chromosomal theory of the heredity (see) making the main maintenance of C. Fundamental laws of heredity were formulated by G. Mendel (see Mendel laws) in 1865 and confirmed in 1900 by Korrens (To. Correns), E. Tscliermak and X. de Fris. In the last quarter of 19 century the major discoveries in studying of chromosomes were made. So, it was open that chromosomes are an obligatory component of a kernel of cells of plants (I. D. Chistyakov, 1874) p animals (P. I. Peremezhko, 1879; V. Flemming, 1879) that number p

a form of chromosomes for each species of plants or animals are constant [Rabl (To. Rabi), 1885; Boverp (Th. Boveri), 1887], Strasburger (E. Strasburger, 1875), Wang - Benede - number (E. van Beneden, 1883), O. Geert Whig (1884) and V. I. By Belyaev it was established that a set of chromosomes in somatic cells double, prp formation of mature sex cells decreasing to unary and recovered to double at fertilization. The first ideas of participation of cells (see the Cell), in particular their kernels, in transfer of heritage expressed Gertvig and Strasburger in 1884 and were developed and proved by Wilson (E. V. Wilson) in 1896. For the first time existence of possible communication between hereditary factors and chromosomes was assumed by Ru (W. Roux, 1883),

A. Veysman and Korrens (1900 — 1902). Comparison of manifestation of signs during the crossing of organisms with behavior of chromosomes in a gametogenesis and at fertilization led W. S. Sutton and Boveri in 1903 — 1904 to the first experimentally reasonable formulation of the chromosomal theory of heredity. Chromosomes were considered as carriers of hereditary factors, on later terminology — genes (see the Gene), and splitting, separation and new association of genes in generations of organisms found an explanation in separation, free discrepancy and a new combination of parent chromosomes. The chromosomal theory of heredity received final confirmation after were established communication of the specific genes defining

a sex (see) organism, with special — sexual — chromosomes; the linked inheritance of characters as a result of existence of genes in the form of several groups which are physically connected with each other, so-called linkage groups, to-rye correspond to chromosomes; at last, the cases of inheritance of not linked genes which received an explanation after establishment of existence of exchanges of sites of homologous chromosomes in meiosis (see). Thanks to works of researchers of school of T. Morgan the provision on the linear strictly fixed arrangement of genes in chromosomes was proved and the principle of drawing up genetic maps of chromosomes is developed (see. The chromosome map) on the frequency of the recombination (see) the genes which are in them occurring thanks to conjugation of chromosomes (see) and krossingove-RU-

the Second period of development of C. (since the end of the second decade on the 60th 20 century) it is possible to characterize as the period of a research of material bases of heredity it is preferential on microscopic (light microscopy) and submicroscopic (submicroscopy) levels. Intensively developed in this period C. plants, animals and the person modern sections of the general

Ts. V S. G. Navashin's works, G. A. Levitsky were also created, L. N. Delon, etc. importance of a research of morphology of mitotic chromosomes was proved (see the Mitosis), in particular identity of a structure of couples of chromosomes is established and by that it is reasonable morfol. principle of identity of chromosomes. As a result of numerous observations the universal two-humeral structure of chromosomes was open (see). From 30th

20 century the morphology and function of so-called heterochromatinic and other specialized regions of chromosomes (the nucleolar organizer, a kinetochore) is intensively studied. Use of a submicroscopy made possible studying of ultrastructure of a metaphase chromosome, in particular packagings of huge molecules DNA, and interfazny chromatin (see). Also electronic microscopic examination of transformations of chromosomes gained distribution in meiosis svetooptichesky; structural bases of a crossing-over were so open (see Conjugation of chromosomes). In the 50th 20 century on earlier opened polytene chromosomes and chromosomes like lamp brushes began to investigate a structure of individual sites of chromosomes in the course of a transcription (see). There was a so-called functional morphology of chromosomes. Thanks to development by Taylor (J. N of Taylor) a method of an autoradiography (see) chromosomes in C. the separate direction — the studying of a reproduction of chromosomes (see) including questions of transfer of patterns of matrix synthesis of DNA from molecular level on a chromosome as cytologic structure, chronology of a reproduction of different chromosomes of set and certain sites on length of individual chromosomes, etc. was created. The genetic mapping of chromosomes begun by Morgan and his pupils remains to one of the main directions of researches in C., the purpose to-rogo is creation of genetic maps of chromosomes of representatives specific biol. types.

The research of influence of x-ray emission on chromosomes laid the foundation for studying of mutagens (see) and a chromosomal mutagenesis (see). Classification of restructurings of chromosomes was developed, their features at different types of organisms are established and under different conditions of influence of radiation, and also origins of such mutations and their genetic effects. In the solution of these problems the essential contribution was made by the Soviet scientists V. V. Sakharov, M. E. Lobashev, I. A. Rapoport, N. P. Dubinin, H. N. Sokolov, B. N. Sidorov, V. V. Hvostova, etc. Domestic researchers M. S. Navashin, G. A. Levit-sky, G. D. Karpechenko, A. N. Lutkov, etc. in the 20th 20 century first-ever began studying of genomic variability of organisms, i.e. changes of chromosome number in set or numbers of the whole unary full ranges — polyploidies (see Chromosomal complement). Works of these scientists laid the foundation for a research of a role of genomic variability in natural speciation and artificial creation of new forms and plant varieties and breeds of animals. Cytogenetic studying of initial parent forms helped with creation and selection of valuable polyploid forms of cultivated plants numerous hozyaystvenno. The researches based on experimental doubling of chromosomal complements in sex cells of hybrids of different types of plants helped to overcome infertility of such hybrids and led to creation of new types, forms and grades of cultivated plants by method of the distant hybridization (see).

Works of S. G. Navashin and his pupils of G. A. Levitsky, L. N. Delon and M. S. Navashina on thin morphology of chromosomes of plants promoted development of one more direction in C. — kariosistemati-k and to clarification of a role of transformations of chromosomes (change of their number, form and ploidy) V EVOLYUTSION

of NOMAS formation biol. types (see Phylogenesis). The Soviet cytogenetics of school of S. G. Navashin and N. K. Koltsov from 20th 20 century began extensive researches of chromosomes of systematic units of plants and animals. In the next years these researches were continued by Whyte (M. J. D. White), R. Matt hey, etc. Within this direction C. studies also individual variability of chromosomes at individuals of one look (see. Chromosomal polymorphism).

The third period in the history of C., begun since the end of the 60th of 20 century, it is characterized by the fact that studying of the problems put earlier in all sections C. it is more and more transferred to molecular level. It is possible to call this period molekulyarnotsitogenetichesky. The received data are generalized in comparison to the data obtained earlier. A herald of molecular approach to clarification of structure of a chromosome and its functions was N. K. Koltsov, to-ry in 1927 — 1928 offered a hypothesis of a molecular structure and a reproduction of a chromosome. According to this hypothesis a basis of a chromosome the elaborate linear macromolecule capable to self-reproduction avtokatalitichesko-go makes in the way constructions of the copy on an initial molecular matrix. Experimental studying of the chemical nature of hereditary material began in the 30th 20 century with cytochemical definition of the main biol. macromolecules in a cellular kernel: proteins (see), DNA and RNA (see. Nucleic acids). In the 40th 20 century by means of photometry (see) and the AI spectrophotometer (see) keeping in cellular structures of DNA and RNA was quantitatively studied. Development of biochemistry (see) and physical chemistry nucleinic to - t and proteins led to studying of chemical structure of chromosomes and cellular kernels by methods of physical chemistry (see), analytical and preparative biochemistry, results to-rykh are stated in A. N. Belozersky, A.S. Spirin, G. P. Georgiev, I. B. Zbarsky, E. Chargaff's works, A. E. Mir-sky, D. Davidson, Levene (Ph. A. Th. Levene), Astberi (W. T. Astbury), etc.

With discovery of spatial structure of molecule DNA F. Shout and J. Watson, and then and the chemical nature of a genetic code (see) there was a modern molecular genetics from a takikhma important for C. methodical approaches, as fractionation and fragmentation of the general DNA of a genome and DNA of individual chromosomes or sites of an interfazny kernel by means of the managed denaturation — a renatura-tion of DNA, an uljtratsentrifugirovaniye (see) in a gradient of density of solutions of salts and processings by nucleases (see); cloning and reproduction of fragments of DNA in bacterial cells, definition of primary nucleotide sequence in fragments of molecule DNA; hybridization of nucleic acids in solutions, on filters and in tsitol. drugs of chromosomes. All this provided association of methods of molecular genetics with traditional methods of studying of the structurally functional organization of chromosomes. As a result begin to receive an explanation at molecular level such functions of chromosomes as a transcription (see), replication (see), a recombination at a crossing-over, mechanisms of reorganizations of chromosomes and a reparation of damages of DNA (see the Reparation of genetic damages), the nature of mitotic condensation — dekondensation of chromosomes and other phenomena. Along with classic methods of genetic mapping since the beginning of the 80th of 20 century began to be applied (first of all in C. person) methods of direct molecular mapping of individual chromosomes and their sites. At the same time existence of considerable mezhin-dividualny polymorphism of people on the nucleotide sequences of segments of DNA identical on localization in a homologous chromosome became clear. Comparative study of the unique and repeating nucleotide sequences of DNA at sibling species of organisms is an essential contribution molecular C. in a kariosistematika and in an explanation of mechanisms of evolution of genomes biol. types.

The direct relation to theoretical and applied medicine has C. the person, edge especially intensively began to develop in the third period of history C. Since the end

of 19 century, since separate attempts to see chromosomes in cells of the person, searches of methodical approaches to morfol began. to a research of chromosomes of the person. The most essential contribution to development of C. the person was brought by works of the Soviet cytogeneticists A. G. Andres, P. I. Zhivago, G. K. Hrushchova, M. S. Navashin, etc., to-rye in the 30th 20 century the first applied to receiving drugs of chromosomes quickly cultivated culture of leukocytes and impact on cells hypotonic solution; they for the first time described a structure of 10 largest chromosomes of the person, made attempts of the analysis of a condition of chromosomes in tumor and leukemic (blast) cells, and also in an oogenesis. These researches were conducted by hl. obr. in Medicogenetic in-those of A. M. Gorky, functioning in the USSR in 1932 — 1937. After final definition of total number of chromosomes in cells of the person (46 instead of 48) and establishments of their morphological features formation of C. person as section C. ended. As a result of development of a technique of the analysis of drugs of the integral cultivated cells divided from each other after a stop of their division in metaphase of a mitosis by means of colchicine and processing hypotonic solution began studying of morphology of mitotic and meiotic chromosomes for the purpose of identification of individual chromosomes of set and their certain sites, and also a research of polymorphism and a reproduction of chromosomes and a chromosomal mutagenesis. In 1959 it was established that an etiology of Down (see Down a disease), Shereshevsky's syndromes — Turner (see Turner a syndrome) and Klaynfeltera (see Klaynfelter a syndrome) is a deviation of chromosome number from normal.

In the late sixties were developed 20 century new methods of studying of thin morphology (linear differentiation of structure) of mitotic chromosomes, molekulyarnogenetichesky methods of a research of chromosomes (molecular mapping), methods of genetics of somatic cells (see) — use of hybrids of somatic cells for allocation of individual chromosomes. It provided further development of researches on structural and functional morphology of individual chromosomes and their certain sites, genetic and molecular mapping of chromosomes, studying of evolution of chromosomes of the person, etc.

After discovery of so-called chromosomal diseases (see) began to develop intensively clinical C., engaged in studying of a role of chromosomes in an etiology and a pathogeny of inborn malformations, disturbances of sexual development, malignant

niya of a novoobrazov, etc.

Special value for medicine has the section C. the person, devoted to clarification of value of individual chromosomes and their certain sites in emergence of disturbances of development in the person in ontogenesis. In the course of development of this direction C. the significant influence of change of ploidy of a zygote, chromosome number or their structure on pre-natal mortality, the birth of children with multiple malformations, disturbance of sexual development and infertility was established. The chromosomal analysis became a component of inspection of the majority addressing in medikogenetichesky consultations (see) and medical institutions concerning infertility, usual not incubation of pregnancy, a delay of sexual development, the birth of children with malformations and mental retardation. Suspicion of chromosomal diseases is the main indication for carrying out prenatal diagnosis.

One of the most intensively developing sections C. the cytogenetics of tumors is. She studies character and a role of disturbances of a karyotype (see) at emergence and development of tumors (see) and leukoses (see). Ancestor Ts. tumors consider Boveri the who the first suggested that the changes of chromosomal complement of somatic cells resulting from anomalies of a mitosis are the reason of cancer. In the purposeful studying of chromosomes in tumor cells begun in 20 — the 30th there are 20 century, the big role was played as idesei Boveri, and further progress of C. and experimental oncology.

Development of C. tumors it is connected with improvement of methods of receiving chromosomal drugs. The possibility of identification of each chromosome allowed to catch both numerical, and structural changes in separate chromosomes and their sites, i.e. to create conditions for the detailed analysis of changes of a karyotype at different malignant new growths. Still in 50 — the 60th 20 century certain consistent patterns of kario-typical variability in populations of the cultivated cells of tumors and leukemic cells and its difference from changes of a karyotype were determined at chromosomal diseases of the person. Karioti-pichesky heterogeneity of cell population is characteristic of tumors. Degree of manifestation of this heterogeneity varies both within tumors of the same localization, and between tumors different gistol. types and localizations whereas at chromosomal diseases all cells, except for cases of mosaicism (see), have an identical karyotype. During growth and a progression of tumors (see) their chromosomal characteristic quite often changes, and at chromosomal diseases of evolution of a karyotype, as a rule, do not observe.

The genetic heterogeneity and variability of neoplastic populations which are the cornerstone of a phenomenon of a tumoral progression cause ability of cells, fittest to unfavorable conditions of the environment, to survival. So, emergence of resistance of a tumor to radiation or medicinal therapy is connected with the selection survival and reproduction kle-


current, resistant to these influences.

In 1960 the first specific change of a karyotype was revealed at hron. a myeloleukemia of the person — the shortened chromosome from group G. This chromosome was called Philadelphian (Ph) according to the name of the city where it was for the first time described. It was established later that the Ph-chromosome is available for 90 — 95% of patients hron. a myeloleukemia that allowed to use results of the cytogenetic analysis for specification of the diagnosis of this disease.

Progress in development of C. tumors came after emergence of methods of differential coloring of chromosomes. For several years specific chromosomal changes in cells of nek-ry tumors of the person and a lab were open. animals. Mostly it is translocations (see), sometimes shortage or redundancy of number of certain chromosomes. Though, according to different data, chromosome mutations are found at hemoblastoses and tumors in unequal percent of cases, they are specific to certain forms of malignant new growths. So, e.g., the translocation between chromosomes of the 15 and 17 couples meets only at an acute promiyelotsitarny leukosis whereas the translocation between chromosomes of the 4 and 11 couples is found only in patients with an acute lymphoblastoid leukosis (fig. 1).

The translocation between chromosomes of the 8 and 21 couples is characteristic of an acute myeloleukemia. In cells of a lymphoma of Berkitt irrespective of presence or absence of Epstayn's virus at it — Burra is observed a translocation between chromosomes of the 8 and 14 couples. At unilateral retinoblastomas the specific marker — an isochromosome 6 r, i.e. the chromosome consisting of the connected short shoulders (fig. 2) is found. It is present at cells of a retinoblastoma along with two normal homologs of the 6th couple. At chalk -

Fig. 1. A karyotype of a leukemic cell at an acute lymphoblastoid leukosis:

the translocation, specific to this leukosis, is visible: transfer of the site of a long limb of the 4th couple (4q —) on a long limb of the 11th couple (liq +).

kokletochny cancer of a lung specific deletion of a certain site of a short limb of the 3rd couple is described. Number of new growths, at to-rykh are revealed specific anomalies of a karyotype, every year increases.

Fig. 2. Change of a karyotype characteristic of a retinoblastoma:

an isochromosome 6r, consisting of the connected short limbs of the 6th couple (on the right), and two normal homologs of this chromosome (at the left). Above and below — chromosomes from cells of different tumors.

Along with specific changes not casually often come to light at separate forms of tumors different mutations of nek-ry chromosomes. So, e.g., lack of one of gonosomes is quite often observed in leukemic cells at an acute myeloleukemia, and in cells at a number of leukoses and tumors participation of a chromosome of the 1st couple in different reorganizations of a karyotype is noted.

Though over the last 10 years in C. tumors there are achievements big, than for all previous years of its development, in essence, the detailed picture of changes of a karyotype at various leukoses and tumors only begins to appear. However the obtained data it is enough that not only to speak about a nonrandom role of chromosome mutations in a carcinogenesis, but also to begin to use results of the cytogenetic analysis for specification of the diagnosis and the forecast of malignant new growths. It already becomes concerning the hemoblastoses of the person representing cytogenetically the most studied group of malignant new growths.

In 1983 it was established that activation of cellular oncogenes as a result of their hit at chromosomal translocations to the area of actively functioning DNA can play, apparently, a part in proliferation and a malignancy of cells. In this field of theoretical oncology cross and mutually virologic, molecular and genetic and cytogenetic researches supplement each other.

Problems C. are developed generally in research establishments where researches on genetics (see) and cytology are conducted (see). In the USSR of such institutions are among Ying t the general genetics of Academy of Sciences of the USSR, Ying t a pier -

lyarny biology of Academy of Sciences of the USSR, Ying t of a tologiya and geneticists of the Siberian division of Academy of Sciences of the USSR, Ying t of cytology of 1 USSR, Ying t of developmental biology of L of the USSR and nek-ry others, and also felts of biology and genetics of high fur boots, ditsinsky and >selskokhozyaystven-x in-t of the country. Problems C. doveka and medical C. zanima-\I preferential Ying t medicine of genetics of the USSR Academy of Medical Sciences, and also to-rye other AMN institutions [WEDNESDAY, M3 of the USSR and the ministries (a ravookhraneniye allied respub-to. C. it is taught as a part of Retiki's course or biology with bases ^етики on biol. faculties of gt, in medical and сельскохо-^ственных in-ta. Heads and razde-z on C. are available in all otechest-yany and translated managements to the 7th genetics or cytology. In the USSR Cang a number of monographs on the general and £тной to cytogenetics, including «Osno-) cytogenetics of the person» under c. A. A. Prokofjeva-Belgovskoy] 169), «Chromosomes of the person (probna of the linear organization)» of A. F.) harova (1977), «Chromosomes чело-^а. The atlas» A. F. Zakharova (see: 15, additional materials) et al.;» 82).

The main periodic the edition on C. Ge — a *gika magazines of Academy of Sciences of the USSR, «Cytology and >1etika» are AN of USSR, «Cytology») 1 USSR. Abroad articles on C. Experimental Cell ^search», «Human Genetics», «Journal ^Medical Genetics», «American Jour-j of Medical Genetics» ride in «Canadian Journal of jnetics and Cytology», «Chromoso-t», «Clinical Genetics», «Cytogenetics id Cell Genetics», «.

Zliogr.: The East To. and Sumner 3. emosoma of an eukaryotic cell, lane zgl., M., 1981; In and l with about N E. B. Klet-l her role in development and heredity. with English, t. 1 — 2, M. — JI., 1936 — 1940; x and r about in A. F. Chromosomes of the person, 1977; 3 and x and r about in A. F. and d the river Hro-omy of the person, the Atlas, M., 1982; Kohn-antinov A. B. Cytogenetics, claim, 1971; Kuznetsoval.E. and. Chromosomal disturbances in cells of an inoblastoma, Vopr. onkol., t. 28, No. 5, 17, 1982; Tumoral growth as a problem of a logiya of development, under the editorship of V. I. Gel-; yn, page 115, M., 1979; Pogosyants

E. New in cytogenetics of cancer, Geneti-t. 17, No. 12, page 2087, 1981; Prigo-[N of an E. JI., etc. Clinical znache-! chromosomal changes at acute goats, Probl. gematol. and modulation, mole. 27, No. 11, page 10, 1982; P r about to about f-a-Belgovskayaa. A. Dostizhe-[cytogenetics in 50 years in the USSR, the Gene-and, No. 10, page 86, 1967; The Management according to 'Ologiya, under the editorship of A.S. Troshin, t., 2, M. — L., 1965 — 1966; Svensson Merzt. and to Young. Cytogenetics. with English, M., 1969; Chromosomal abnor-lities and their clinical significance in te lymphoblastic leukemia, Cancer Res., 43, p. 868, 1983; Comparative mamma-i cytogenetics, ed. by K. Benirschke, a. o., 1969; HsuT. C,

Human and mmalian cytogenetics, An historical spective, N. Y., 1979;

Mitelman i. L e v a n G. Clustering of aberrations specific chromosomes in human neoplasms, 'editas (Lund), v. 95, p, 79, 1981;

R i e-ger R., M i with h an e H s A. Green M. M. Glossary of genetics and cytogenetics, Classical and molecular, Jena, 1976; Rowley J. D. Human oncogene locations and chromosome aberrations, Nature (Lond.), v. 301, p. 290, 1983; Sandberg A. A. The chromosomes in human cancer and leukemia, N. Y., a. o., 1980; Swanson C. P. Cytology and cytogenetics, L., 1958; Therman E. Human chromosomes, N. Y. a. o., 1980.

Periodicals — Genetics, M., since 1965; Cytology, JL, since 1959; Cytology and genetics, Kiev, since 1967; American Journal of Medical Genetics, N. Y., since 1977; Canadian Journal of Genetics and Cytology, Ottawa, since 1959; Chromosoma, B. — Wien, since 1939; Clinical Genetics, Copenhagen, since 1970; Cytogenetics, Basel, since 1962; Experimental Cell Research, N. Y., since 1950; Human Genetics, Amsterdam, since 1962; Journal of Medical Genetics, L., since 1964.

A. F. Zakharov; E. E. Pogoyeyants (cytogenetics of tumors).