[In situ hybridization in human genome mapping]. / Gibridizatsiia in situ v reshenii problemy kartirovaniia genoma cheloveka.

The methodological possibilities of non-radioactive in situ hybridization of nucleic acids and its application for an immediate localization of genes and chromosomes are discussed. The advantages of a non-isotope probe labeling versus a use of radioactive substances are emphasized. Various types of compounds used as a label are distinguished. The principles of use of the above labels and the ways to improve the method in terms of increasing its sensitivity are considered. Some results obtained while using non-radioactive labelled probes are reported. It is shown promising to use this method for molecular-genetic analysis of DNA polymorphism in human genome.

[Study of polymorphism in human rRNA gene clusters. Population and familial analysis of basic types of RFLP]. / Issledovanie polimorfizma v predelakh klaster genov rRNK cheloveka. populiatsionnyi i semeinyi analiz osnovnykh tipov PDRF.

The frequency and average amount of copy number per genome were defined for standard and a number of new variants of BamHI 5'-NTS RFLP from populations of Moscow, Riga and individuals with Down syndrome. It was demonstrated that the populations studied differ neither in population frequency nor in the average amount of copy number of the variants. New variants were detected in the EcoRI 3'-NTS RFLP system and their amplification, as well as discordance among MZ twins. Possible target for methylation in the HindII site of 3' end of 28S rRNA gene was revealed. Analysis of data obtained demonstrated inefficiency of using the RFLP systems in systematic mapping of NOR-chromosomes. Our data also suggested a possible role of amplification of one copy repeated unit rRNA genes in their evolution.

[Study of polymorphism in human rRNA gene clusters]. / Issledovanie polimorfizma v predelakh klastera genov rRNK cheloveka.

Human ribosomal DNA (rDNA) probe specific for the 3' end of the 28S rRNA gene was used for detecting standard restriction fragments' length polymorphism (RFLPs) in the non-transcribed spacer. The conditions for hybridization of rDNA probe which eliminate cross hybridization of parts of 28S rRNA gene were developed. A test for detecting incompletely restricted DNA was also developed which may be used in experiments for detecting new RFLPs. It was found that a set of standard RFLPs was identical in various human tissues for one individual. Frequency of standard RFLPs in the non-transcribed spacer of human rRNA gene clusters was calculated.

[Genetico-demographic patterns of the prevalence of various forms of endogenous psychoses]. / Genetiko-demograficheskie zakonomernosti rasprostraneniia razlichnykh form éndogennykh psikhozov.

Prevalence rates (PRs) for EFP (schizophrenic, schizoaffective and affective psychoses), with allowance for proband sex and age-of-onset data were studied in a subdivided population from the North-East of the European Region of the USSR. The population includes three subpopulations: a small old religious semi-isolate of Russians ("Rs"), aboriginal Komi people ("Ks")--an ethnic community of Ugro-Finnish lineage, and a mixed group of migrants ("Ms") from various regions of the USSR. The latter is mainly an urban population, while the "Rs" and "Ks" are, on the whole, rural populations. The total PR for EFP was found to be 0.97% for the "Rs", 0.63% for the "Ks" and 0.35% for the "Ms", whereas PRs-0.85-1.15% in other parts of the USSR, mainly for "panmixed" populations in large towns. The lower PRs for EFP in the "Ms" is caused by a backmigration flow involving certain groups of patients; consequently, the mean liability for "Ms" offsprings (as a whole) should also be lower. On the other hand, the lower PRs for EFP in the "Ks" is caused by underpresentation of clinically mild cases of the mental disease (mainly, pseudoneurotic schizophrenia), especially among female patients, probably due to that the so affected persons are sufficiently adapted to the cultural traditions of this rural population. It was shown that in the "Rs" the total PR for "nuclear" and paranoid schizophrenia is 0.68% versus 0.25% in a "panmixed" population. The increase is most likely caused by the high inbreeding level in the "Rs" semi-isolate, and if this is correct, we may suppose that at least one or two recessive genes are involved in the liability to the most heavy forms of schizophrenia. On the other hand, in the "Ms" (as in other "panmixed" populations) positive assortative mating among hereditary-predisposed persons is a more significant factor influencing family transmission of EFP, since the correlation between probands and their spouses is rpp = 0.31 (p less than 0.001) in the "Ms", as compared to rpp = 0.19 (p less than 0.1) in the "Rs". Thus, our general conclusion is that neither the place of inhabitance nor the life mode are the causal factors for EFP, but rather some genetic factors, more accurately, certain sets of specific genes.

[A method of analyzing the chromosome localization of repetitive nucleotide sequences by using hybridization in situ]. / K metodike analiza khromosomnoi lokalizatsii povtoriaiushchikhsia nukleotidnykh posledovatel'nostei s pomoshch'iu gibridizatsii in situ.

To increase precision in the quantitative analysis of chromosomal distribution of repeated DNA sequences detected by in situ hybridization, a number of factors important in studies of the molecular basis of chromosome polymorphism should be considered. While analysing results of hybridization, one should only use the number of grains over the sites of their regular localization, instead of those over the whole chromosome. It is also evident that to decrease variability conditioned by differences in the labelling degree of separate cells, the relative numbers of labelled grains over chromosomes should be used in the analysis and not the absolute ones. Data from those cells ought to be only included in the analysis, in which the labelling degree is sufficient to show all localization sites of the repeated sequences studied, i.e. cells should be used with comparatively constant relative numbers of labelled grains over all their regular localization sites.

[Genetic analysis of predisposition to cancer of the stomach]. / Geneticheskii analiz predraspolozheniia k raku zheludka.

The results of a complex family and population epidemiologic study of gastric cancer pointed to inheritance as an important factor of the incidence of this disease. However, there may be different combinations of genetic factors, on the one hand, and genetic and environmental ones, on the other, versus age and sex. This should be considered in conducting screening for families at genetic risk for stomach cancer and taking measures aimed at eliminating carcinogenic factors which increase the likelihood of familial cancer incidence. Such considerations should contribute to a certain degree to early diagnosis and prevention of the disease.

[Clinico-genetical studies of colonic cancer. III. Primary multiple malignant neoplasms]. / Kliniko-geneticheskie issledovaniia raka tolstoi kishki. Soobshchenie III, Pervichno-mnozhestvennye zlokachestvennye novoobrazovaniia (PMZN).

The results of clinico-genealogic analysis of 46 patients with primary-multiple malignant neoplasms are given (among them 16 patients with primary-multiple malignant neoplasms of colon cancer and 30 patients with one or more neoplasms in combination with different malignant tumors of other organs). The values of segregation rates obtained for primary-multiple malignant neoplasms are lower than theoretically expected for simple monogeneous types of inheritance. The relation analysis of primary-multiple malignant neoplasms and colon cancer revealed that these tumors are likely to appear among relatives of probands under the influence of the same genetic system of determination. Risk of the colon cancer development for relatives of the patients with primary-multiple malignant neoplasms is higher than for relatives of the patients with colon cancer.

[Clinico-genetical studies of colonic cancer. II. Genetic analysis of predisposition to colonic cancer]. / Kliniko-geneticheskie issledovaniia raka tolstoi kishki. Soobshchenie II. Geneticheskii analiz predraspolozheniia k raku tolstoi kishki.

The structure of subjection to different clinical forms of colon cancer and to the morbidity as a whole approximates better the quasi-continued phenotypical model within which the contribution of genetic factors reaches 68-84%, that of incidental medium factors being 16-32%. Genetic study of heterogeneity of colon cancer clinical forms revealed that their pathogenetic community was quite high. However, the origin of colon cancer depends strongly on genetic factors (83.7 +/- 7.3%), in comparison with rectal cancer (67.9 +/- 7.1%). The analysis of colon cancer interrelation with other malignant neoplasms (including specific ones for women--breast and uterus cancer) revealed that the development of another malignant neoplasms was the result of the influence of partially common genes (20-50%) which predetermined the development of colon cancer and other malignant neoplasms. According to the data obtained in this study, the tables of repeated risk have been worked out which may be used for medico-genetic consultation.

[Clinico-genetical analysis of colonic cancer. I. Occurrence, frequency in families and segregation analysis]. / Kliniko-geneticheskoe issledovanie raka tolstoi kishki. Soobshchenie I. Rasprostranennost', semeinoe nakoplenie i segregatsionnyi analiz.

The data on clinico-genealogic studies of colon cancer are presented. 694 families were examined with 432 probands having rectal and 262 colonic carcinoma among them. Clear family accumulation of colon cancer (2.4 +/- 0.35%) as well as other malignant tumors (6.8 +/- 0.6%) (p less than 0.01) was shown among the relatives of the first degree of relation. The values of segregation rates obtained for clinical forms of colon cancer were lower than theoretically expected for simple monogenic types of inheritance. The analysis of incomplete penetration of genotypes showed that, though formally the inheritance of colon cancer and its clinico-anatomical forms may be described by quasi-dominant types of inheritance, the penetration values are very low: from 4.3 to 13.3% for homozygotes and from 2.1 to 6.6% for heterozygotes. It shows that the supposition about the monogenic types of the colon cancer inheritance is doubtful and suggests that the colon cancer is to be regarded on the basis of the multifactorial model.

[Cloned fragment of human alphoid DNA--a molecular marker of the pericentromeric region of chromosome 18]. / Klonirovannyi fragment al'foidnoi DNK cheloveka--molekuliarnyi marker pritsentromernogo raiona 18-i khromosomy.

From the library of cloned fragments of human DNA we have isolated two recombinant plasmids containing alphoid DNA sequences pBRHS13, pBRHS65. Both cloned sequences hybridized in situ predominantly to pericentromeric regions of chromosome 18 and with less intensity to pericentromeric regions of chromosomes 2, 9, 20, and were characterized by populational copy number polymorphism in homologous chromosomes. These sequences may appear very useful in the diagnostics and cytogenetic analysis of chromosomal aberrations and in studies of polymorphisms of heterochromatic regions of human chromosomes.

[Molecular approaches to the systematic mapping of the human genome]. / Molekuliarnye podkhody k sistematicheskomu kartirovaniiu genoma cheloveka.

A review of current progress in human gene mapping methods is presented. The advantages and restrictions of several mapping methods are discussed. The main bulk of the review is concerned with perspectives of using special collection of "molecular-genetic markers" (MGM). These are cloned nucleotide sequences which allow to find population (and family) polymorphisms in three structural characteristics of homologous DNA fragments: in length, in regional chromosome location, in the number of local copies. Accordingly, three groups of MGM are analysed: (i) unique genome fragments, (ii) mobile dispersed genes and (iii) clustered DNA repeats. As the authors suggest, the second one has to be the most available tool for recognition of mother and father partners in all chromosome pairs. It is an important step to the progress in mapping not only monogenic traits but polygenic characters too, including multifactorial diseases in man.

[Structural analysis of the Alu-containing DNA fragment with disperse distribution in human chromosomes]. / Strukturnyi analiz Alu-soderzhashchego fragmenta DNK s dispersnym raspredeleniem v khromosomakh cheloveka.

Nucleotide sequencing of two terminal subfragments of a cloned human DNA fragment has been done. The fragment cloned hybridized dispersively along all chromosomes except for Y chromosome and C heterochromatic chromosome regions. Both subfragments sequenced contain Alu repeats, whose structures differ partially from those of accurately determined sequences of human Alu repeats. The results obtained are discussed in respect of possible usage of Alu repeats containing sequences for construction of special polymorphic molecular markers of human chromosomes.

[Risk of schizophrenic spectrum psychoses among the offspring of affected mothers and fathers (comparative epidemiologic study)]. / Risk zabolevaemosti psikhozami shizofrenicheskogo spektra v potomstve bol'nykh materei i ottsov (sravnitel'noe épidemiologicheskoe issledovanie).

Comparative epidemiological study in population of patients with schizophrenia in one of the Moscow regions revealed differential morbidity risk in posterity. Convincing proofs obtained showed sick children with schizophrenia prevalence in sick mothers, but not fathers' posterity. Such a conclusion on the representative populational material was made for the first time. The study showed the specificity of differential morbidity risk in control groups of patients with other disease entities analyzed. Different factors significance in so-called "maternal effect" manifestation are discussed.

[Genetic-correlation analysis of schizophrenic syndromes]. / Genetiko-korreliatsionnyi analiz sindromal'nykh form shizofrenii.

Two hundred and seven families of patients with schizophrenia were examined. Diagnosis of the disease in probands and relatives was made according to the syndromal forms of schizophrenia. The simple, catatonic, hebephrenic and paranoid forms of the disease were distinguished. Current genetic-correlation analysis demonstrated marked genetic correlation between the disease forms. This makes the above-mentioned classification of schizophrenia inadequate for special genetic studies aimed at the definition of factors that determine the development of different clinical forms of the disease.

[Concordance in twins and the component partition of phenotypic variance in schizophrenia]. / Konkordantnost' u bliznetsov i komponentnoe razlozhenie fenotipicheskoi dispersii pri shizofrenii.

The paper deals with a study of the pairwise and proband concordance rates to schizophrenia in 36 monozygotic (MZ) and 87 dizygotic (DZ) twins. Pairwise concordance rate to manifestative forms of schizophrenia was 0.54 and 0.18 for MZ and DZ twins, respectively, but when broader diagnostic criteria were used, the values were 0.73 and 0.27. Proband concordance rate in MZ twins was 0.70. The results of component partition of phenotypic variance show a leading role of a genotypic additive component in the development of schizophrenia (56.1%) and significance of the specific twin paratypic component. A conclusion is made on the leading role of genotypic factors in schizophrenia.

[Table method of the component expansion of phenotypic variance based on correlations between relatives]. / Tablichnyi metod komponentnogo razlozheniia fenotipicheskoi dispersii na osnove korreliatsii mezhdu rodstvennikami.

Tables are proposed which allow to ease and unify calculations of component partitioning of the phenotype variance based on the "least squares methods". Combinations of additive and dominant genetic components and four common environmental ones are considered. To use tables, information is needed about correlations among following types of relatives: 1) MZ and DZ twins, parent-offspring; 2) siblings, parent-offspring, second degree relatives; 3) the first variant and sibling; 4) the third variant and second degree relatives.

[Table method of component partition of phenotypic dispersion for identifying the X chromosome effect based on correlations between relatives]. / Tablichnyi metod komponentnogo ralozheniia fenotipicheskoi dispersii dlia identifikatsii éffekta X-khromosoma na osnove korerliatsii mezhdu rodstvennikami.

The tables are proposed which allow to ease and to unificate component variance partitioning based on the "least squares method" in the case of sex-linked genes effect. This approach is directed to partial solving of tasks when the given correlations do not allow the complete component partition. Variants are considered for additive gonosomic variance identification, for additive and dominant autosomic variances and common environmental components for twins. To use these tables, the existence of correlations among twins or offspring-parent and siblings discriminated by sex is needed.