Previous research using microdensitometric scanning and computer graphic image analysis showed that T-banded segments of human metaphase chromosomes usually exhibit an asymmetrical distribution of high density (HD) chromatin between sister chromatids. Here, we employed the same methods to analyze HD chromatin distribution at opposite ends of T-banded human lymphocyte chromosomes. This study revealed that in most chromosomes with an asymmetrical distribution of HD chromatin at both ends, the highest densities of each arm were located in opposite chromatids. The frequency of this configuration was 0.792 per chromosome, indicating that the highest chromatin densities of the terminal segments of T-banded human chromosomes were non-randomly distributed at opposite chromosome arms. The possible relationship of this observation to the mode of replication of the terminal chromosome region is briefly discussed.

We described spontaneous minute sister chromatid exchanges (SCE) in telomeric regions of human and Chinese hamster ovary (CHO) chromosomes more than 10 years ago. These structures, which we called t-SCE, were detected by means of highly precise quantitative microphotometrical scanning and computer graphic image analysis. Recently, several authors using the CO-FISH method also found small SCEs in telomeric regions and called them T-SCE. The use of different terms for designating the same phenomenon should be avoided. We propose ter SCE as a uniform nomenclature for minute telomeric SCEs.

Los recientes progresos tecnológicos ocurridos en citogenética molecular han permitido la detección de numerosas minúsculas aberraciones en la región cromosómica contigua al telómero o segmento subtelomérico, que han sido relacionadas con diversos cuadros de retardo mental, malformaciones congénitas y otros síndromes de interés médico. Investigaciones previas, llevadas a cabo mediante exploración microfotométrica y análisis gráfico computacional del subtelómero, revelaron diferentes patrones de distribución de las densidades de la cromatina y la existencia de intercambios sumamente pequeños entre cromátidas hermanas en dicho segmento cromosómico. La detección de aberraciones crípticas sindromáticas, el elevado número de intercambios cromosómicos y las observaciones microscópicas sobre la estructura subtelomérica sugieren que reflejan la gran actividad genómica y la complejidad estructural prevalente en la región. En la presente revisión se describen brevemente varios síndromes cromosómicos subteloméricos, así como la estructura molecular y citológica de la región subtelomérica y las principales funciones del segmento cromosómico terminal a fin de brindar un panorama general sobre esta área de investigaciones en rápido crecimiento de considerable significación biomédica

Résumé Les derniers progrès technologiques en cytogénétique moléculaire, ont permis de repérer de nombreuses et minuscules aberrations dans la région chromosomique du télomère ou segment subtélomérique liées au retard mental, des malformations congénitales et d’autres syndrômes d’intérèt médical. Des recherches antérieures, menées à bout au moyen d’exploration microphotométrique et d’analyse graphique par ordinateur du subtélomère, ont montré de différents paramètres de distribution des densités de la chromatine et l’existence de minuscules échanges entre chromatides soeurs dans ce segment chromosomique. La détection d’aberrations cryptiques syndromatiques, le grand nombre d’échanges chromoso-miques et les observations microscopiques de la structure subtélomérique suggèrent une grande activité génomique et la compléxité structurelle prévalente dans la région. On décrit ici brièvement plusieurs syndrômes chromoso-miques subtélomériques, ainsi que la structure moléculaire et cytologique de la région subtélomérique et les principales fonctions du segment chromosomique terminal, afin d’offrir un panorama général sur cette sujet de recherches qui s’accroit considérablement

Summary Recent technological advances occurred in molecular cytogenetics have allowed to detect numerous minute aberrations in the chromosome region contiguous to the telomere or subtelomeric segment which has been related to various conditions of mental retardation and congenital malformations and to other clinical syndromes of medical interest. Previous research on the subtelomere carried out by means of scanning microphotometry and computer graphic analysis, revealed different patterns of the distribution of chromatin densities and the existence of minute exchanges between sister chromatids in this chromosomic segment. The detection of cryptic syndromatic aberrations, the high number of chromosome crossovers and the microscopical observations on the subtelomeric structure suggest that they reflect the great genomic activity and the structural complexity prevailing in the region. In the present review, several subtelomeric chromosome syndromes, the cytological and molecular structure of the subtelomeric region as well as the main functions of the chromosome terminal segment are briefly described in order to give a general panorama on this fast growing research area of considerable significance in bio-medicine

Se exponen, desde una perspectiva histórica y en forma sucinta, los sistemas de identificación de los cromosomas humanos y varios métodos de bandeo cromosómico desarrollados en las últimas cuatro décadas. Se relatan ámbitos y hechos acontecidos -varios de los cuales protagonizó el autor- que originaron la actual moderna citogenética estructural y molecular. Se mencionan, asimismo, algunos aspectos moleculares implícitos en estas metodologías con el propósito de contribuir al esclarecimiento de los variados aspectos revelados por dichos métodos sobre las estructuras cromosómicas subyacentes. Se describen también los procedimientos analíticos desarrollados en nuestro laboratorio para el estudio de núcleos y cromosomas como así los resultados obtenidos sobre el análisis cuantitativo de la región subtelomérica y su probable relación con las aberraciones crípticas, detectadas en dicho segmento cromosómico, productoras de retardo mental y malformaciones congénitas. Finalmente, se realiza un breve relato sobre las aplicaciones del bandeo cromosómico en el proyecto del genoma humano y su posible utilidad en los experimentos de síntesis artificial de núcleos celulares eucarióticos, de particular significado en biología.

Résumé On montre, depuis une perspective historique, les systèmes d'identification des chromosomes humains et plusieurs méthodes de marquage chromosomique développées pendant les quatre dernières décades. On décrit des faits et des circonstances -dont l'auteur a été souvent protago-niste- qui ont été à l'origine de l'actuelle cytogénétique structurale et moléculaire. On fait aussi allusion à quelques aspects moléculaires implicites dans ces méthodologies afin de contribuer à expliquer de divers aspects des structures chromosomiques révélés par ces méthodes. On fait la description des procédés analytiques développés dans notre laboratoire pour l'étude de noyaux et de chromosomes ainsi que les résultats obtenus sur l'analyse quantitative de la région subtelomérique et son rapport avec les aberrations cryptiques repérées dans le segment chromosomique qui sont la cause de retard mental et de malformations congénitales. Finalement, on fait un bref descriptif sur les applications des bandes chromosomiques dans le projet du génome humain et sa possible utilité dans des expériments de synthèse artificielle de noyaux eucaryotes, de grande importance en biologie.

Summary Human chromosome identification systems and several chromosome banding methods, developed during the last four decades, are briefly reviewed under a historical perspective. Numerous episodes that built the basis of the present modern structural and molecular citogenetics (the author took part in some of them) are reported. Some molecular aspects related to this methodology are also mentioned, in order to contribute to the understanding of different aspects of the underlying chromosomal structures revealed by these methods. The analytical procedures developed in our laboratory for the study of nuclei and chromosomes, the results of quantitative analysis of the subtelomeric region and its probable relationship with cryptic aberrations detected in this chromosomal segment and responsible for mental retardation and congenital abnormalities, are described. Finally, we also include a brief report about the application of chromosome banding in the Human Genome Project and on its potential usefulness in the development of experiments on the artificial synthesis of eukariotic cell nuclei, of considerable significance in biology, is also included.

Empregaram-se técnicas de escaneamento microfotométrico e análise de imagem gráfica computadorizada para detectar a distribuição de densidades de cromatina em segmentos subteloméricos de cromossomos endo-reduplicados com bandeamento T de células do ovário do hamster chinês (CHO). Os padrões de densidade de cromatina detectados com este método foram similares aos previamente encontrados em CHO e cromossomos humanos normais. As densidades de cromatina mais elevadas foram consideradas como segmentos marcadores que levaram à detecção de alterações recíprocas de posição de cromossomos endo-reduplicados durante o espalhamento das células na lâmina. O problema dos padrões de densidade de bandeamento T subteloméricos encontrados nos cromossomos endo-reduplicados e sua relação com a estrutura e a composição molecular desta região é discutido brevemente.

Microphotometrical scanning and computer graphic image analysis were carried out to detect the distribution of chromatin densities in subtelomeric segments of T-banded endoreduplicated chromosomes of Chinese hamster ovary (CHO) cells. Chromatin density patterns detected with this method were similar to those previously found in CHO and normal human chromosomes. The highest chromatin densities were considered as marker segments which led to the detection of reciprocal changes of position in endoreduplicated chromosomes during cell spreading on the slide. The problem of the subtelomeric T-banding density patterns found in the endoreduplicated chromosomes and their relation to the structure and molecular composition of this region is briefly discussed.

Chromatid gaps and breaks induced by the restriction endonucleases AluI and BamHI in the long arm of chromosome 1 of Chinese hamster ovary cells were microphotometrically scanned and mapped to a quantitative G-band map. More than 50% of chromatid breaks appeared as chromatin losses of greater than 5% of the total arm length. The majority of chromatid gaps and breaks as well as chromatin losses induced by both restriction endonucleases were non-randomly located in a region from 0.35 to 0.65 relative length units of the long arm of chromosome 1. We suggest that the access of these endonucleases to chromosomal DNA depends on the local organization of the chromatin.