Characterization of a Gene Expressed during Human Myeloid Cell Differentiation

Lamb, Richard Forsyth (1990) Characterization of a Gene Expressed during Human Myeloid Cell Differentiation. PhD thesis, University of Glasgow.

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Characterization of a gene expressed during human myeloid cell differentiation Previous work using differential screening of a cDNA library representing poly A+ RNA from the peripheral blood leukocytes of a chronic phase CGL patient had led to the isolation of cDNA clones representing mRNAs found at high abundance in this leukaemia compared to ANLL, CLL or normal peripheral blood leukocytes. The gene encoding one clone, pCG14, was also found to be expressed during normal human myelopoiesis in the neutrophilic myelocyte, a bone-marrow restricted neutrophil progenitor. In this work the pCG14 cDNA was completely sequenced and shown to encode HNP3, one of a group of three closely homologous peptides called defensins. These peptides are found in abundance in the granules of neutrophils and are involved in destruction of micro-organisms. The human defensin peptides HNP1 and HNP3 were shown to be encoded by two mRNAs differing at only one coding position that could be distinguished by PCR, and the regulation of the abundance of these mRNAs during myelopoiesis was investigated using induced differentiation of HL60 cells as a model system. Four different genes, two encoding HNP1 and two encoding HNP3, were isolated and one gene encoding HNP1 was characterized in detail. It was shown to be comprised of three exons and its 5'-regulatory region shown to contain two functional promoters. Using the presence of a single nucleotide change which distinguishes the coding regions of HNP1 and 3 genes, giving rise to a polymorphic Hae3 restriction enzyme site, individuals were shown to contain variable relative amounts of HNP1 and HNP3 genes. To explain these results it was hypothesized that individuals contain four defensin genes per diploid cell, one tandem pair on each chromosome 8. This model was tested using DNAs from a family where it was shown that defensin genes were inherited as a pair.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Genetics, Cellular biology
Date of Award: 1990
Depositing User: Enlighten Team
Unique ID: glathesis:1990-78182
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:37
Last Modified: 30 Jan 2020 15:37

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