Expression of the familial hypercholesterolemia gene in heterozygotes: model for a dominant disorder in man

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Abstract

Little is known about the biochemical mechanisms by which dominant genes act. Nearly all of the hereditary metabolic disorders characterized at the molecular level have proved to be due to specific enzyme deficiencies inherited in a recessive pattern. In these recessive disorders the half normal enzyme activities that occur in heterozygotes are sufficient to prevent clinical disease. For dominant disorders, this type of metabolic reserve does not exist and heterozygotes are clinically affected. For this reason, McKusick has suggested that dominant mutations are likely to involve abnormalities not in enzymes, but in nonenzymic proteins such as those that are postulated to regulate complex metabolic pathways. Recently it has been shown that one dominant disorder, Familial Hypercholesterolemia, is due to a mutation involving a regulatory protein. An analysis of the expression of this regulatory defect in heterozygotes has provided new insight into one mechanism for dominant gene action in man.

Original languageEnglish (US)
Title of host publicationTransactions of the Association of American Physicians
Pages120-131
Number of pages12
Volume87
Publication statusPublished - 1974

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ASJC Scopus subject areas

  • Medicine(all)

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