Relationship of the variability of the heterochromatic regions of chromosomes 1, 9, 16, and Y to some anthropometric characteristics in children with embryopathies of unknown etiology and in children with Down syndrome

Summary The relationship between variability of the heterochromatic regions of chromosomes 1, 9, 16, and Y, and anthropometric characteristics (length and mass of body, shoulder diameter) in 70 children with embryopathies of unknown etiology and in 40 children with Down syndrome was studied. The positive statistically significant correlations of the C segment lenghts of chromosomes 1, 9, 16, their sum included, and the above characteristics were found. The correlation coefficients of Y chromosome were not significant. The questions of the functional role of the structural heterochromatin and its influence on the viability and physical development of the organism are discussed.     

Analysis of centromere size in human chromosomes 1, 9, 15, and 16 by electron microscopy.

Human chromosomes were treated with 5-azacytidine and analyzed by whole-mount electron microscopy. This base analogue produces undercondensation of heterochromatin and separation of the centromere from the bulk of pericentromeric heterochromatin in chromosomes 1, 9, 15, and 16, which allows clear delimitation of the centromere regions. A quantitative analysis of centromeres showed that chromosomes 1, 9, and 16 have centromeres of different size. The centromere of chromosome 15 is similar in size to that of chromosome 9 and different from those of chromosomes 1 and 16. No interindividual variation for centromere size was found. A positive correlation between centromere and chromosome size was found for the chromosomes analyzed.     

Heterochromatic regions on chromosomes 1, 9, 16, and Y in children with some disturbances occurring during embryo development

Some reduction of C-segment lengths and their variability on chromosomes 1, 9, 16, and Y was exhibited by children who had had some disturbances at early stages of morphogenesis. The data obtained might suggest a certain activity of the heterochromatic regions during embryo development. Based on this data one may also suppose that reduction of the amount of heterochromatin might affect the normal morphogenetic processes.     

The quantitative analysis of polymorphism on human chromosomes 1, 9, 16 and Y

Summary The generalized characteristic of the C-segment lengths on chromosomes 1, 9, 16, and Y is suggested for a study of population heterogeneity. For this purpose, the concept of the distance D is introduced, taking into account the individual C-segment lengths, the mean lengths and standard deviations of C-segment lengths in a group of subjects, as well as the coefficients of correlation of the C-segment lengths on the said chromosomes.It is demonstrated that distance D may be employed to study the relevance of the given subject to the group studied, the relation to the mean characteristics within the group, and selection of subjects' pairs with almost identical C-segment lengths on respective chromosomes.In the study of such problems as zygosity of twins, family analysis, etc., along with the absolute C-segment lengths, it is recommended to employ the relative C-segment lengths on chromosomes 1, 9, 16, and Y, calculated as a part of the sum total of their absolute lengths.     

The quantitative analysis of polymorphism on human chromosomes 1, 9, 16, and Y

This study was made to establish a stable quantitative characteristic of C segments on chromosomes 1, 9, 16, and Y in an individual karyotype that was reproducible in successive experiments. The C segment of these chromosomes were measured in successive cultures of cells from three males and the C segments of chromosomes 1, 9, and 16 in cells from three pairs of female monozygotic twins were measured. The results show that the absolute lengths of C segments tend to vary considerably with the cell samples analyzed, while the relative length, i.e., the length of a single C segment as a percentage of the total length of all C segments of the chromosomes being studied, is more stable and can be used for individual characteristics.     

Heterochromatic regions and the nondisjunction of human chromosome 21. I. Polymorphism of the C-bands of chromosomes 1, 9 and 16 in children with Down's syndrome

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.     

The segregation of C-band polymorphisms on chromosomes 1, 9, and 16.

Eleven normal families with at least four children were studied cytogenetically using the C-band technique to identify polymorphisms in the constitutive heterochromatin of chromosomes 1, 9 and 16. Thirteen individuals showed one or more variants in such chromosomes. The analysis of the segregation ratios in the 35 offspring of these 13 individuals showed that these marker chromosomes generally segregated according to the expected 50:50. However, one of these variants, chromosome no. 9 with an increased heterochromatin block in the secondary constriction, has an apparently preferential segregation, when the findings from this study are combined with those of other authors.     

Polymorphism of human chromosomes 1, 9, 16, Y: Variations,segregation and mosaicism

Summary A study was carried out on C-banded chromosomes 1, 9, 16, Y from an unselected population and from 30 normal families. We found: a) great variability in length and position of the C-bands; b) somatic mosaicism involving C-bands; c) variants in children that were not present in parental patterns. The possible role of crossing-over in generating the last two phenomena is discussed.     

C-band length variability and reproductive wastage

Summary The possible influence of total Y chromosome length and the C-band size variability of chromosomes 1, 9, 16, and Y, on reproductive wastage was investigated. One hundred couples with recurrent reproductive wastage and 106 control couples with at least two healthy children and no miscarriages were cytogenetically studied. Total Y chromosome length was evaluated as the Y/F index and the C-band size was analyzed quantitatively according to the linear measurement method of Baliek et al. (1977). The different degrees of mitotic contraction were corrected on the basis of the linear correlation found between heterochromatin and euchromatin length. Statistical comparison between results of Y chromosome from both samples demonstrated, in the test group, an increase in the mean value of the Y/F index, but the increase of Y C-band length did not reach significance. In addition mean values of C-band length on chromosomes 1, 9, and 16 in couples from the test group and especially those who had had two or more abortions, were lower than those in the controls. Among the latter the frequency of chromosomes included in the category of very large heterochromatin size is higher. However these length differences have been demonstrated only in specific subgroups, and in each one for a different chromosome. Our results indicated that Y chromosome length as well as C-band size variabilities are not directly related to reproductive wastage.     

C-polymorphism of chromosomes 1, 9, 16 and Y in newborn infants of various gestational ages

Comparative evaluation of absolute C-segment lengths of chromosomes 1, 9, 16 and Y in new-born children of different gestational age has revealed no significant differences in their value between individuals with unfinished intrauterine development and those born in time.     

Analysis of the inheritance of heterochromatic regions in human chromosomes 1, 9, 16 and Y

The inheritance of heterochromatic regions of chromosomes 1, 9, 16 and Y was studied in twelve families by means of measuring their C-segments. Maternal and paternal origin of chromosomes 1, 9 and 16 in the child was determined by two methods. The advantages and disadvantages of these methods and possibilities of their application are under discussion.     

Patterns of exchange induced by mitomycin C in C-bands of human chromosomes. I. Relationship to C-band size in chromosomes 1, 9, and 16

Summary Frequencies of exchange were determined in C-bands of chromosomes 1, 9 and 16 in six normal males, and related to relative C-band area. Comparing these different chromosomes, more exchanges occurred on average in 9 than in 1 although their mean C-band sizes were similar. Chromosome 16 exchanges were fewer, both overall and relative to C-band area. Comparing the same chromosome between individuals, there was a positive correlation between relative frequency and band size in both 1-1 and 9-9 exchanges. No clear trend was observed for other exchange events.If homology is required for interchange, if cannot be dependent solely on overall C-band size. Perhaps certain DNA sequences, sensitive to mitomycin C damage, are located in part of each C-band, with less per unit area in chromosome 1 than in 9 and still less in chromosome 16.X- and U-type exchanges between chromosome 9s occurred in near equal frequencies in all individuals. If synapsis of specific, affected sequences is a pre-requisite for interchange, this observation suggests that the affected sequence in chromosome 9 is arranged in both orientations relative to the centromere.     

Equivalence of the total constitutive heterochromatin content by an interchromosomal compensation in the C band sizes of chromosomes 1, 9, 16, and Y in Caucasian and Japanese individuals

A quantitative analysis of C bands by densitometric measurements in chromosomes 1, 9, 16, and Y was conducted in Caucasians and Japanese living in Brazil. Sixty normal unrelated subjects (30 males and 30 females) were studied in each racial group. Caucasians presented C bands of chromosomes 1, 9, and 16 larger than Japanese, but, on average, only the difference for C bands of chromosome 9 was statistically significant. In the Japanese, the C band sizes of chromosomes Y were, on average, significantly larger than in the Caucasians. The mean C band size of chromosome 9 and the sum of the three pairs were significantly larger in Caucasian than in Japanese males. The total values of constitutive heterochromatin, sigma (1qh,9qh,16qh,Yq12), did not show significant difference between Caucasian and Japanese males. The relative C band sizes of chromosomes 1, 9, and 16 were, on average, similar in Caucasians and Japanese. No sex difference was found in both racial groups. As regards the heteromorphism, only the values of C bands of chromosome 9 were, on average, significantly larger in Caucasians than in Japanese. Partial inversions were detected only among the Caucasians.     

An attempt to define 1qh+, 9qh+, and 16qh+

Summary The lengths of the secondary constrictions of chromosomes 1, 9, and 16 vary with the degree of contraction of the chromosomes but these constrictions contract to a lesser degree than the euchromatic portions of the chromosomes. The regression coefficient for the regression of the length of the secondary constriction on the length of the euchromatic part of the chromosomes is shown to be larger for large constrictions. It is furthermore shown that there is a linear correlation between the regression coefficient and the size of the secondary constriction in question. This linear correlation makes it possible to correct the lengths of the secondary constrictions to the lengths expected when contraction is average. The correction method is used in a sample of 30 couples, and on the basis of this sample, the normal limits for the lengths of the secondary constrictions in chromosomes 1, 9, and 16 are defined.     

Quantitative analysis of C bands in chromosomes 1, 9, and 16 of Brazilian Indians and Caucasoids

Summary Densitometric C-band measurements in chromosomes 1, 9, and 16 of 394 Indians and 40 Caucasoids living in Brazil are reported. No significant intratribal variability in the average length of these regions was observed, and the intertribal variation showed no consistent patterns. But the Caucasoids always presented lower means. The relative C-band sizes of these three chromosomes, however, were very similar in Indians and Caucasoids. The indices of heteromorphism displayed analogous results; only in chromosome 16 are they dissimilar in these two ethnic groups. An unexpected sex difference was observed in the C-band sizes of this chromosome, females uniformly presenting higher averages than males. Centromeric heterochromatin appeared in 6% and 9% respectively of the short arms of chromosomes 1 and 9 among the Caucasoids, while among the Indians its prevalence was 2% in both chromosomes.     

Quantitative assessment of human chromosomal polymorphism with regard to paracentromeric heterochromatin

The measurement of C-segment length in chromosomes 1, 9 and 16 of 7 individuals was carried out. The regression analysis was employed to study a change of the C-segment sizes in the process of mitotic chromosome condensation. Typical values of C-segment length for chromosomes 1, 9 and 16 are about 1.4, 1.1 and 0.8mu respectively. Among 7 individuals there was no two which had identical size of C-segments for all three chromosomes studied. In six individuals heteromorphysm of C-segments was revealed. It was found that visually detected heteromorphysm may be expressed quantitatively as ratio length of C-segments in homologous chromosomes.     

Quantitative analysis of C-segments of chromosomes 1, 9, 16 and Y in couples with reproductive disorders

A comparative analysis of structural variability of C-bands on chromosomes 1, 9, 16 and Y was conducted in 50 phenotypically normal adults and 25 couples with repeated spontaneous abortions. Reduction of both the total amount of heterochromatin in the cell and the lengths of these regions on chromosomes 1, 9, and 16 is revealed in the group of pathology. No differences were found in the lengths of C-bands on Y chromosome.     

Heterochromatin is not an adequate explanation for close proximity of interphase chromosomes 1--Y, 9--Y, and 16--Y in human spermatozoa

Analysis of human spermatozoa and lymphocytes using C-banding techniques and in situ hybridization has shown a higher order packaging of the human genome. Chromosomes are not distributed entirely at random within the nucleus. In particular, chromosomes 1, 9, and 16, carrying large blocks of pericentromeric heterochromatin, and the Y chromosome, carrying heterochromatin in Yq12, are in close proximity to each other within the nucleus and are involved in somatic pairing with nonhomologous chromosomes. In order to determine whether the close proximity of these chromosomes in any way is attributable to the distribution of heterochromatin, double in situ hybridization was performed on chromosomes 1--Y, 9--Y, and 16--Y as well as on 1--X, 9--X, and 16--X-with chromosome X as the other gonosome carrying less heterochromatin-in human spermatozoa. Each pair was found to have a nonrandom spatial distribution. However, comparison of the arrangement of chromosomes 1--Y versus 1--X and 9--Y versus 9--X revealed that heterochromatin cannot be the only cause for the tendency of chromosome fusion, because only the results of the chromosome pair 1--Y/1--X could support this proposition. In conclusion, the heterochromatin effect cannot be, in itself, an adequate explanation for chromosome association, implicating as well other mechanisms.     

Centromeric instability of chromosomes 1, 9, and 16 associated with combined immunodeficiency

Summary Instability of the centromeric regions of chromosomes 1, 9, and 16 in cultured lymphocytes of an 8-month-old girl with malabsorption and combined immunodeficiency is reported. Together with the two previous reports on this condition, the present report seems to confirm the specific association of combined immunodeficiency and centromeric instability of chromosomes 1, 9 and 16 with multibranching.