Genetic determination of rheumatoid arthritis. Distribution of certain Mendelian markers in the light of correspondence of the disease heritability to the model of single autosomal two-allele locus with incomplete penetrance

The study on the nature of distribution of certain mendelian markers aimed at specifying their role in determination of rheumatoid arthritis disease was carried out, based on the material from the Family Data Bank of the Department of Epidemiology and Genetics of the rheumatic diseases in this institute comprising data on 200 families of patients with definite rheumatoid arthritis (RA). Antigens of HLA-system (the loci A, B, DR), ABO blood groups, Rh, MN and P, phenotypes of acid erythrocyte phosphatase and the types of haptoglobin were studied. Based on the data from this and the previous studies, it is established that the steadiest deviations of the RA patients groups from the general population concerned the frequency of HLA A11, B12, B27 and DR4, blood group P and phenotypes of the acid erythrocyte phosphatase. When using additional controls--a group of healthy mothers of women-probands from the families with the type of marriage "healthy x healthy", and analysing some pair combinations of the HLA system antigens, it was demonstrated that the most clearly their role in formation of the disease display the antigens DR4, and in their absence--DR3, and B12, whereas accumulation of A11 and B27 depended on the presence of other antigens of HLA loci--A and B. Taken together, these data may imply that genetic markers under study serve, when in certain combinations, as "modifiers" of the major gene, or, in a general case, of major genes of multifactorial disease affecting its appearance and clinical manifestations.     

Genetic determination of rheumatoid arthritis

The study on the nature of genetic determination of the definite rheumatoid arthritis (RA) and its forms was carried out, based on the material comprising clinical data on 189 probands and their 1st and 2nd degree relatives (713 subjects) which is contained in the computer Family Data Bank at the Department of Epidemiology and Genetics of this institute. The heritability coefficient "in narrow sense" (80%) obtained within the framework of the multifactorial threshold model confirmed once more important role of genetic factors in the appearance of the disease. The study of genetic heterogeneity within the framework of the Ch. Smith's and T. Reich's models failed to reveal any independent genetically RA forms. An assumption of the essential role of the genes localized in the X chromosome, based on diverse susceptibility of sexes, received no conformation. It has been shown that the RA distribution in the population and families may well be described by means of a variant of the single autosomal two-allele locus model with incomplete and differentiated for two sexes penetrance. The model parameters obtained, a particular penetrance of the mutant homozygote in both sexes equalling 100%, and penetrance of the normal homozygote equalling 0 in men and reaching 0 (0.028%) in women testify to a very essential influence of the major gene on determination of RA.     

Use of the integral parameter of dermatoglyphic differences for determining the type of zygosity of twins]

A method is described increasing the reliability of twin zygosity diagnosis in cases when the possibility of using a large number of mendelian markers is restricted. The method is based on the determination of generalized index of dermatoglyphic differences between members of twin pair for 18 characteris of finger and palm dermatoglyphics and on principles of multivariate genetic analysis, which is worked out to determine the degree of heritability of multifactorial character and to study the structure of hereditary predisposition to multifactorial diseases. The efficiency of the method with respect to determinating the type of twin zygosity is approximately equivalent to the efficiency of using 5--6 mendelian marker systems.     

Metabolism of Yarrowia lipolytica Grown on Ethanol under Conditions Promoting the Production of α-Ketoglutaric and Citric Acids: A Comparative Study of the Central Metabolism Enzymes

A comparative study of the enzymes of tricarboxylic acid (TCA) and glyoxylate cycles in the mutant Yarrowia lipolytica strain N1 capable of producing -ketoglutaric acid (KGA) and citric acid showed that almost all enzymes of the TCA cycle are more active under conditions promoting the production of KGA. The only exception was citrate synthase, whose activity was higher in yeast cells producing citric acid. The production of both acids was accompanied by suppression of the glyoxylate cycle enzymes. The activities of malate dehydrogenase, aconitase, NADP-dependent isocitrate dehydrogenase, and fumarase were higher in cells producing KGA than in cells producing citric acid.     

A genetic analysis of endocrine diseases of the thyroid and pancreas

The genetic determination of insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus and thyroid gland diseases (TGD) was carried out using clinical-genealogical data on 229 patients with IDDM, 275 patient with NIDDM, 247 patients with TGD and their relatives. Results of component decomposition showed the role of genetic factors in the determination of these diseases and the existence of interloci interaction in genetic control of IDDM and NIDDM. The genetic independence of these diseases and genetic homogeneity of NIDDM were revealed using models of Ch. Smith and T. Reich.     

Mathematical modeling of citric acid production by repeated batch culture

A mathematical model has been created for the process of citric acid biosynthesis by yeast (mutant strain Yarrowia lipolytica) cultivated by the repeated batch (RB) method on ethanol under conditions of nitrogen limitation. The model accounts for cell growth as a function of nitrogen concentration in the culture liquid; nitrogen uptake by growing cells; citric acid production; pH control in the fermentor by means of NaOH addition; and changes in system volume. The model represents a system of five nonlinear differential equations. Experimental measurements of cell concentration, citric acid concentration, and cultivation broth volume were used with the least squares method to determine the values of eight model parameters. The parameter values obtained were consistent with literature data and general concepts of cell growth and citric acid biosynthesis. The model has been used to predict optimum RB culture conditions.     

Emulsifying activity of yeasts growing on normal alkanes

The ability to emulsify n-hexadecane was compared among ten strains of Candida lipolytica. The cultures were shown to differ in the activity of emulsification. The highest activity was recorded in the phase of growth deceleration. Substances involved in n-alkane emulsification were isolated.     

Characteristics of the growth on rapeseed oil and synthesis of citric and isocitric acids by <Emphasis Type="Italic">Yarrowia lipolytica</Emphasis> yeasts

The native strain Yarrowia lipolytica VKMY-2373 grown in a complete medium exhibited the maximum lipase activity at the concentration of rapesseed oil of at least 5.0 g/l. In the course of yeast growth, no considerable changes were observed in the glycerol concentration, the proportions of the major free fatty acids formed via oil hydrolysis, or the fatty acid composition of oil. Under nitrogen limitation of cell growth, the accumulation of citric acids reached 77.1 g/l with predominance of isocitric acid at pH 6.0, whereas at pH 4.5, almost equal amounts of citric and isocitric acids were produced. Cultivation of the mutant strain Y. lipolytica N 1 at pH 4.5 resulted in the predominant accumulation of citric acid (66.6 g/l) with an insignificant amount of isocitric acid. In the period of intense acid synthesis, high production of lipase was observed.     

Synthesis citric and isocitric acids by Yarrowia lipolytica during yeasts growth on rapeseed oils

The native strain Yarrowia lipolytica VKM Y-2373 grown in a complete medium exhibited the maximum lipase activity at the concentration of rapeseed oil of at least 5.0 g/l. In the course of yeast growth, no considerable changes were observed in the glycerol concentration, the proportions of the major free fatty acids formed via oil hydrolysis, or the fatty acid composition of oil. Under nitrogen limitation of cell growth, the accumulation of citric acids reached 77.1 g/l with predominance of isocitric acid at pH 6.0, whereas at pH 4.5, almost equal amounts of citric and isocitric acids were produced. Cultivation of the mutant strain Y. lipolytica N 1 at pH 4.5 resulted in the predominant accumulation of citric acid (66.6 g/l) with an insignificant amount of isocitric acid. In the period of intense acid synthesis, high production of lipase was observed.     

Ethanol metabolism in the yeasts Yarrowia and Torulopsis (a review)

Results of research into ethanol metabolism in yeast organisms with highly pronounced aerobic metabolism are reviewed. The low activity of NAD-dependent alcohol dehydrogenase (EC 1.1.1.1), observed under the conditions of aerobic yeast growth on ethanol, demonstrates that alternative enzyme systems--alcohol oxidase (EC 1.1.3.13), microsomal ethanol-oxidizing system (including cytochrome P-450), and catalase (EC 1.11.1.6)--may be involved in the alcohol oxidation. The role of these systems in alcohol oxidation and conditions favoring their operation in this processes are analyzed. It is concluded that iron ions are important regulators of ethanol metabolism the microorganisms of this group.