Summary
Some modern concepts of the operational structure of chromosomes in higher organisms are discussed. The importance of models is stressed, in which the bands and interbands of giant chromosomes are regarded as functional units of gene action. This means also that, besides the classic structural genes, there are much more extensive DNA sites with a regulatory function.
Three hypotheses are discussed:
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1.
The phenotypes of chromosome aberrations syndromes are not caused by too many or too few classic structural genes, but by disturbances in the function of regulatory DNA sites.
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2.
The minute mutants of Drosophila melanogaster can be explained in an analogous way. Therefore they can be used as models for an examination of genotype-phenotype relationships in regulatory disturbances.
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3.
In this connection, a third hypothesis was discussed, according to which the almost complete lack of symptoms of the usual autosomal dominant conditions in cases with autosomal deletions is caused by the fact that for these autosomal dominant conditions, an interaction between normal and abnormal polypeptides is required.
The hypotheses are discussed, and possible ways of examining them are indicated.
Zusammenfassung
Zunächst wurden einige moderne Auffassungen über die operationelle Struktur der Chromosomen höherer Organismen diskutiert. Dabei werden insbesondere diejenigen Modelle in den Vordergrund gestellt, die die Banden und Interbanden der Riesenchromosomen als funktionelle Einheiten der Genwirkung betrachten und außerdem neben den klassischen Strukturgenen wesentlich umfangreichere DNS-Abschnitte mit übergeordneter Kontrollfunktion annehmen.
Sodann werden drei Hypothesen diskutiert:
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1.
Die Symptomatik der durch Chromosomenaberrationen verursachten Syndrome beim Menschen ist im wesentlichen nicht durch Fehlen oder überzähliges Vorhandensein klassischer Strukturgene, sondern durch Störungen in der Funktion von DNS-Abschnitten mit regulatorischer Funktion bedingt.
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2.
Die Minute-Mutanten von Drosophila melanogaster sind analog zu erklären; sie eignen sich daher als Modelle für eine Untersuchung der Genotyp-Phänotyp-Beziehungen bei derartigen Regulationsstörungen.
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3.
In Zusammenhang damit wurde eine dritte Hypothese diskutiert, wonach das fast völlige Fehlen von Symptomen der üblichen autosomal dominanten Erbleiden bei Fällen mit sichtbaren Deletionen von Autosomen darauf zurückzuführen ist, daß für das Entstehen dieser autosomal-dominanten Erbleiden eine Interaktion zwischen normalem und abweichendem Polypeptid erforderlich ist.
Die Hypothesen werden diskutiert, und es werden Möglichkeiten für ihre Prüfung angegeben.
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This paper is dedicated to Hans Grüneberg, on his retirement from the Chair of Animal Genetics at University College, London.
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Vogel, F. Genotype and phenotype in human chromosome aberrations and in the minute mutants of Drosophila melanogaster . Hum Genet 19, 41–56 (1973). https://doi.org/10.1007/BF00295234
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DOI: https://doi.org/10.1007/BF00295234