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Inborn errors of metabolism: Clues to understanding human behavioral disorders (1976)

Omenn, Gilbert S.

Springer

Behavior genetics 6 (1976), S. 263-284

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ISSN: 1573-3297

Keywords: review ; biochemical disorder ; genetic diseases ; abnormal behavior ; metabolic pathways ; inborn erros (of metabolism)

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Psychology

Notes: Abstract Detailed behavioral and biochemical investigation of patients with inborn errors of metabolism, especially those intrinsic to the nervous system, may provide many clues to the genetic predisposition underlying human behavioral traits. Relatives of such patients and other individuals with homologous enzymatic lesions due to alleles specifying intermediate activity need to be studied as well. Among the metabolic disorders discussed selectively here, some masquerade as schizophrenia, manic-depressive illness, or hyperactivity syndrome of childhood, providing examples of the striking heterogeneity to be found for these common behavioral disorders.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01065723

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Increase in copy number of an integrated vector during continuous culture of Hansenula polymorpha expressing functional human haemoglobin (1994)

Gilbert, S. C. ; van Urk, H. ; Greenfield, A. J. ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Yeast 10 (1994), S. 1569-1580

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ISSN: 0749-503X

Keywords: Hansenula ; haemoglobin ; integration ; continuous culture ; Life and Medical Sciences ; Genetics

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology

Notes: Recombinant human haemoglobin A (rHbA) was produced by a leucine-requiring strain of Hansenula polymorpha which had been transformed with an integration vector containing the Saccharomyces cerevisiae LEU2 gene and cDNAs for the expression of α and β globin each driven by the H. polymorpha MOX promoter. After 40 generations in a chemostat it was found that the integrated vector had become amplified in the host strain. In some cases this led to an increase in LEU2 gene dosage, but a loss of globin expression cassettes. In other cases the globin gene dosage also increased. These changes coincided with an increase in rHbA production in the culture, which was reversed when the dilution rate was increased. Isolates from a chemostat culture producing elevated levels of rHbA were grown in fed-batch fermentations, resulting in higher productivities than when inoculated with the parent strain. The rHbA produced was purified and characterized. Oxygen binding studies and electrospray mass spectrometry showed that the rHbA had been processed and assembled correctly, and behaved as a fully functional co-operative tetramer.

Additional Material: 7 Ill.