Centromeric heterochromatin instability of chromosomes 1, 9, and 16 in variable immunodeficiency syndrome — a virus-induced phenomenon?

Summary Centromeric instability of chromosomes 1, 9, and 16 has been described in eight patients with variable immunodeficiency. Although the pathogenetic relationship of these cytogenetic abnormalities with the clinical symptoms are unclear, it has nevertheless been proposed that they are a hallmark of this syndrome. Based on the clinical, immunological and cytogenetic data from the literature, a model is presented suggesting that the cytogenetic changes are not causatively involved in the immunodeficiency syndrome, but result from specific virus infections occurring as a consequence of the immunodeficiency in genetically predisposed individuals.     

Multibranched chromosomes 1, 9, and 16 in a patient with combined IgA and IgE deficiency

Summary Instability of the centromeric region of chromosome 1 and multibranched configurations formed by different numbers and combinations of arms of chromosomes 1, 9, and 16 were found in cultured lymphocytes of 12-year-old male with combined IgA and IgE deficiency. No chromosome abnormalities were found in fibroblast cultures from the patient or in blood cultures from his parents.A possible effect on the frequency of the abnormalities of the almost continuous antibiotic treatment received by the patient was found both in vivo and in vitro, but no abnormalities were found in blood cultures from control subjects who received similar treatment. Interphase association of chromosomes 1, 9, and 16 and a high frequency of interchanges among the centromeric regions of these chromosomes due to the presence of a fragile site is assumed to be the cause of the abnormalities.     

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.     

Heterochromatic regions of human chromosomes 1, 9, 16 and Y and the phenotype

The relationship between variability of the heterochromatic regions of chromosomes 1, 9, 16, Y and the anthropometric characteristics (the height, the biacromial diameter and weight) was studied in two groups of children; 70 children had embryopathies of unknown etiology and 40 children had the Down syndrome. The positive statistically significant correlation of the C-segments lengths of chromosomes 1, 9, 16, their sum included, and above characteristics was found. The correlation coefficients of Y-chromosome were non-significant. The problems of functional role of the structural heterochromatin and its influence on viability and physical development of the organism are discussed.     

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.     

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.     

Classification of qh regions in human chromosomes 1, 9, and 16 by C-banding

Summary We present a classification for secondary constriction (qh) regions with C-banding technique in chromosomes 1,9, and 16 by means of comparing them to the short arm of chromosome 16. It is simple and convenient and can be used routinely. It can be incorporated into the modified Paris nomenclature system.     

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.     

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

Summary Comparative analysis of the polymorphism of C segments on chromosomes 1, 9, 16, and Y was conducted in 50 normal boys and 50 normal girls. Quantitative methods revealed that the mean lengths of C segments, their variability, and their distribution on the chromosomes mentioned are quite identical in the two groups. Methodological problems related to the study of chromosome polymorphism are discussed.     

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

Summary A paracentric inversion of chromosome 5 was detected after RHG banding in a subject affected by Klinefelter's syndrome. The inversion was also observed in the patient's mother, and was confirmed by QFQ-and RBA-banding techniques.A second paracentric inversion affecting chromosome 7 was detected in a woman with Turner's syndrome. The same structural anomaly was found in her father and her half-brother.The possible relationship between sex chromosome nondisjunction and paracentric inversion is discussed.Furthermore, the inversion of chromosome 7 reproduces exactly the chromosome 7 of the gorilla, which is presumed to be ancestral to the human 7. This therefore appears to be the first reported case of reverse chromosomal mutation.     

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-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.     

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.     

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.     

Mitomycin C induced structural changes in heterochromatic regions of human chromosomes 1, 9, 16 and Y

Aberrations and variations in the heterochromatic blocks of chromosomes 1, 9, 16 and Y were found under the influence of mitomycin C in cultured lymphocytes of peripheral human blood. Lymphocytes were cultured during 96 hours, mitomycin C in final concentration of 0.3 mkg/ml was present in the culture during the latest 24 hours of culturing. Different changes in the heterochromatic regions of chromosomes were found in approximately 30% of cells: in 6.3% of cells mitotic chiasmata were indicated. In 9.5% of cells isolocus breaks were observed in heterochromatic region of chromosome 1 in segment 1q11. In the latter case this may be a fragile site detected under the influence of mitomycin C on the lymphocytes.     

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.     

Quantitative analysis of C bands in chromosomes 1, 9, 16 and Y in Caucasian and Japanese males

A comparative analysis of the C bands of chromosomes 1, 9, 16 and Y of 27 Caucasian and 27 Japanese males is reported. The mean of the total centromeric heterochromatin of the three pairs (sigma h1, 9, 16) is larger in Caucasian than in Japanese subjects, but Caucasians showed a lower mean of C band size of chromosome Y. Heritability of the C band of the Y chromosome was studied in 26 families.     

Variability of the C-segment sizes of chromosomes 1, 9, 16 and Y in the human chromosome set]

The investigation of chromosome polymorphism by quantitative methods is a rather hard task. The manual method for measuring C-segments of chromosomes 1, 9, 16 and Y in man is suggested, which is not difficult, being reasonably precise for the population research. Metaphases of the average level of chromosome condensation were taken for analysis. Only the C-segments were measured without measuring chromosomes. The negative chromosome image was 4000-fold magnified, compared to the chromosome natural size, and the boundaries of C-segments of each chromosome were five-fold dotted on a sheet of paper specially printed for this purpose. C-segments were measured by magnifying glass with 0.025 mcm scale unit. For every individuum, C-segments were measured in 5-7 cells only. The data are presented on the estimation of measurement errors and on individual (intercellular) and population (interindividual) variations of C-segments of chromosomes.     

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.