Clinical genetics / edited by Arnold Sorsby.

Date:
1953
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Clinical genetics / edited by Arnold Sorsby. Source: Wellcome Collection.

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    CHAPTER 2 PENETRANCE AND EXPRESSION Laurence H. Snyder and Paul R. David SPECIFICITY, PENETRANCE AND EXPRESSIVITY Clinicians recognize that the same aetiological agent (the spirochaete of syphilis, for example) may produce any or several of a variety of effects. There are many familiar instances, also, of' infections which are frankly pathological in some persons, and asymptomatic in others. Furthermore, it is a commonplace that any infectious disease may vary greatly in its severity from one case to another. Analogous phenomena are exhibited in the action of genetic factors. Variation in the kind of effect produced by the same gene or gene complex in different individuals has been designated as variability in specificity ; penetrance is a statistical concept and refers to the frequency with which a characteristic expression of a gene or genotype is manifested among those who possess the gene or genes in question or, sometimes, to the frequency with which any discernible effect at all is exhibited ; expressivity is the degree or severity of expression in a particular individual. The italicized words were first used in these senses by TimoféeflF-Ressovsky (1934) in his studies on Drosophila funebris. The term specificity, in Timoféeff's sense, has not been widely used by other investigators, but penetrance has achieved some currency in the literature of human genetics, and expressivity is occasionally used by authors in this field. More commonly, however, such phrases as irregular expression or variable manifestation are used, and it is usually clear from the context whether the variability referred to relates to type of manifestation (specificity), frequency of manifestation (penetrance), severity of manifestation (expressivity), or to any combination of these. PENETRANCE It is worth remarking at the onset that the terms under discussion, when used without qualification, may be subject to some ambiguity. Thus, if we use the expression incomplete penetrance to imply the occasional absence of any abnormal effect of a given gene or genotype, this must necessarily be understood in a provisional sense, because we can never be certain that we have exhausted all possibilities of detecting the presence of the gene. Hereditary acholuric jaundice, for example, in most pedigrees appears to depend on the presence of an autosomal gene which is regularly manifested in hetero¬ zygotes by jaundice and splenomegaly and the occurrence of acute haemolytic crises which sometimes prove fatal. In a number of the pedigrees, however, the disease occasionally skips a generation, that is, it would appear that the gene has been transmitted from a grandparent who suffered from the disease, through a parent who himself shows none of the clinical signs, to one or more of his grand¬ children in whom the disease reappears. Laboratory examination of the cHnically 9