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The C heterochromatin in chromosomes 1, 9, 16, and Y was studied for 12 families of patients with inherited short stature. A comparison of the results of cytogenetic and genealogical analysis has revealed a correlation between the growth retardation in children and the short stature in parents, and the accumulation of the small C segment in chromosomes 1, 9, and 16 in their karyotypes. These data are entirely consistent with our results obtained for the families having children with gene syndromes (Russell-Silver, Dubowitz etc.) and obligate growth retardation. Obviously, there is a type of narrow height in man associated with the presence of a small amount of C heterochromatin. This appears to be an additional proof of a great importance of C heterochromatin in embryonal and postnatal development. Differential diagnostics of such a type of short stature is important for children endocrinology, since the hormonal growth-stimulated therapy does not have a desirable effect on these patients.

In our previous studies we have demonstrated that the degree of the growth retardation shows a positive correlation with the reduction of C heterochromatin in chromosomes 1, 9, and 16 in patients with embryopathies of unknown etiology and in children with trisomy 21. The investigation of C heterochromatin in these chromosomes in patients with obligate growth retardation and gene syndromes with a postulated Mendelian inheritance (Russell-Silver, Dubowitz etc.) has revealed a reduced C heterochromatin amount. No large C segments were seen in all of the 32 patients. Only 2 large C segments were found in 42 parents that were never inherited. The lowest amount of C heterochromatin was found in the most shortish fathers and mothers. The short stature of healthy parents in patients with the above mentioned syndromes is usually regarded as resulting from an incomplete mutant gene expression. The present results, when taken in conjunction with those of our previous study, enable us to suggest another interpretation: (i) the growth retardation in children with gene syndromes and low height of parents may be due to the reduction of C heterochromatin in chromosomes 1, 9, and 16, i.e. the mutant genes are not the only reason of the growth retardation; (ii) the obligatory growth retardation in the above syndromes can be explained by the fact that the expression of corresponding genes is possible only in genomes with a low C heterochromatin amount; (iii) the C heterochromatin in chromosomes 1, 9, and 16 influences on the number of mutant genes expression in man.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been shown elsewhere that in children with growth retardation and gene syndromes (Russell-Silver, Dubowitz etc.), and in healthy children with inherited short stature the total amount of C heterochromatin in chromosomes 1, 9, and 16 was reduced as compared to the control. A correlation between the C heterochromatin reduction and the intrauterine growth retardation was suggested. A study of C heterochromatin in patients with fetal alcohol syndrome has shown that the chromosome sets of all the 11 children examined are identical to those of the above-mentioned patients. This fact may indicate that a small amount of C heterochromatin may play the leading role in realization of the alcohol effect, since this C heterochromatin deficiency makes the early embryogenesis open to injury to external effects. A possible functional role of C heterochromatin in disturbances of the developmental homeostasis are discussed. These disturbances concern the growth retardation and the lack of resistance to the effect of external and internal factors.

Levels of spontaneous and of C-mitomycine and cyclophosphane-induced chromosome aberrations are determined among the persons not subject to professionally industrial hazards. It has been revealed that in all the experimental series the aberration rate in those, who carried extreme polymorphic variants, was much higher compared to those without these variants in their karyotypes. Among the persons with the above extreme versions, the impact of chromosome ruptures is stronger in the vicinity of the structural heterochromatin. Possible causes of the discovered phenomenon are discussed.

To test a hypothesis on potential role of large heterochromatic regions in chromosome nondisjunction polymorphism of C segments of chromosomes 1, 9, and 16 in 70 children with Down's syndrome were examined. The C segment lengths of the above chromosomes were shown not to deviate from the normal. To solve the problem, it seems unreasonable to examine children with Down's syndrome.

Some differences were observed in the mitotic condensation of regions composing human chromosomes 9 and Y: regions 9p, 9h and Y nf are characterized by an intense condensation by the end of the spiralization interval studied (the length of the repair chromosome 3 varying from 5.4 to 2.9 mkm). At the same time, the condensation of regions 9q-h (region 9q without heterochromatic block) is slowing in the initial spiralization interval (the length of chromosome 3 varying from 16.6 to 5.5 mkm). The Yf-block of Y-chromosome is condensing faster than nf-region. The condensation parameters of Q-heterochromatic blocks are most variable while the euchromatic regions are most stable. The dynamics of 9h and of f-block condensation are independent within one karyotype. Based on the data obtained we doubt the correctness of studies on linear dimensions of the constitutive heterochromatin blocks for the evaluation of its quantity in the karyotype. A possible association of differential mitotic condensation with the chromosome segregation disturbances is discussed.

To test a hypothesis on potential role of large heterochromatic regions in chromosome non-disjunction, a comparative analysis of C segment lengths of chromosomes 1, 9, and 16 in fathers and mothers of children with Down's syndrome was carried out. No difference was found between the two groups. The non-disjunction in mothers is known to occur 4 times as frequently as in fathers. This fact does not allow to suppose that the heterochromatic regions may play a certain part in non-disjunction of chromosome 21.