Application of genetic regulatory mechanisms to human genetics

Parker, Weston; Bearn, Alexander G.

doi:10.1016/0002-9343(63)90107-4

Cited by 39 publications

(8 citation statements)

References 46 publications

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“…The postulated defect could involve regulator gene sites affecting "cis" loci or immunoglobulin gene "repressors" or "activators" that show allelic specificity. There is precedent for defects in regulatory mechanisms from the detailed work of Jacob and Monod on bacteria, but in mammals the action of such genes remains speculative (16). The present data extend current knowledge by emphasizing that quantitative rather than qualitative abnormalities predominate in these families.…”

Section: Resultssupporting

confidence: 64%

Quantitative Abnormalities of Allotypic Genes in Families with Primary Immune Deficiencies

Litwin

Fudenberg

1972

Proc. Natl. Acad. Sci. U.S.A.

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Genetic antigens of human immunoglobulin G (Gm factors) were measured in members of the families of selected patients with primary immunodeficiency. The sera of seven out of 27 heterozygous relatives had either deficient concentrations of one Gm allotype or an unbalanced ratio of Gm(f)/Gm(a). Since these markers for allelic IgG1 genes are found in almost equal amounts in normal heterozygous persons, the results suggested that there was a quantitative deficiency in the expression in serum of one Gm gene. In several families allotype abnormalities were found in three successive generations; in one instance the quantitative defect appeared to segregate independently of the Gm genes. The experimental data failed to support a recessive gene hypothesis, in that too few of the close relatives had evidence indicating that they were carriers of defective Gm genes. The results were interpreted as consistent with an inherited regulatory defect in certain families with this disorder.

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Section: Resultssupporting

confidence: 64%

Quantitative Abnormalities of Allotypic Genes in Families with Primary Immune Deficiencies

Litwin

Fudenberg

1972

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been assumed that apparent lack of an enzyme is most likely due to a regulator gene mutation [33,34]. The better the chemical nature of residual enzyme activity (in blood or tissues) was investigated, the more it became evident, that structural gene mutations may as well lead to enzyme deficiency conditions.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of Erythrocyte Catalase II

Aebi

Wyss

et al. 1974

European Journal of Biochemistry

234

106

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Normal human erythrocyte catalase, when isolated by the method of Mörikofer et al. [Eur. J. Biochem. 11 (1969) 49–57], is heterogenous in two respects: (a) there are alternative molecular forms; (b) besides the active tetramer, enzyme dissociation products (dimer, monomer) are present. By means of exclusion chromatography on Sephadex G‐150 it was shown that catalase preparations contain dimer and monomer in small amounts (∼ 4%). Upon storage, the yield in subunits can be considerably enhanced (up to 15%). Residual catalase activity in the blood of an individual homozygous for Swiss Type Acatalasemia (1–2% of normal level) consists of a catalase variant, which is unstable, but of approximately normal specific activity. In this mutant, the tendency of dissociation into subunits is greatly enhanced. Upon purification, little tetramer but appreciable amounts of the inactive dimer are obtained. The antigenic properties of these molecular species were investigated using anti‐catalase and anti‐catalase‐subunit immunoglobulins G. There is complete antigenic identity between the normal and the variant catalase; the same is true for the normal and variant dimer. Different antigenic properties of dimer and monomer, however, offer evidence for the existence of hidden determinants in the subunits.

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“…One important implication of these newer concepts of genetically derived modulatory complexity (one gene-one polypeptide, one protein, one enzyme, one regulatory mechanism, or some combination) is that both behavioral state and metabolic evidence can traverse a wide range of manifestations depending upon a number of circumstances impinging on the organism at the time of any particular study. Both abnormalities in structural genes (for example, glucose-6-dehydrogenase deficiency) as well as a mutation in a regulatory gene (such as in acute intermittent porphyria) often required a definite environmental trigger (the ingestion of particular drugs) for the manifestation of both the clinical syndrome and its concomitant metabolic changes (96). The various nutritional, hormonal, drug, precursor load, and other influences on mammalian enzyme regulation have been well studied (95).…”

Section: Strategiesmentioning

confidence: 99%