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The salience of Garrod's ‘molecular groupings’ and ‘Inborn Factors in Disease’

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Journal of Inherited Metabolic Disease

Summary

Garrod's important second book,Inborn Factors in Disease (1931), was about inherited predisposition to disease. Chemical and metabolic individuality, which are the modalities of predisposition, originated in ‘molecular groupings’ (proteins) in Garrod's view of life. Such ‘groupings’ as interlocus molecular hybrids, allelic complementation and expressions of modifier genes, can assume variant expression in heterozygotes. Here, it is shown that genetic variation in such ‘molecular groupings’ has clinical relevance, for example (1) in reproductive counselling for thalassaemia; (2) in heterozygosity where the affected enzymes are normally homopolymeric; (3) in clinical severity of ‘monogenic’ disease (e.g. familial hypercholesterolaemia and muscular dystrophy) when variation is not explained by allelic heterogeneity. The associated chemical individuality in each case can be used to identify risk and thus as a mode of predictive medicine.

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  1. deBelle Laboratory for Biochemical Genetics, McGill University-Montreal Children's Hospital Research Institute, H3H 1P3, Montreal, Quebec, Canada

    C. R. Scriver

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From a talk delivered, while I was President, to the 26th Annual Meeting of the Society for the Study of Inborn Errors of Metabolism.

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Scriver, C.R. The salience of Garrod's ‘molecular groupings’ and ‘Inborn Factors in Disease’. J Inherit Metab Dis 12 (Suppl 1), 9–24 (1989). https://doi.org/10.1007/BF01799283

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