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D W Denny

Publications and source records attributed to D W Denny.

5 recordsLinked to original sources
PubMed1985

HLA-B locus polymorphism: studies with a specific hybridization probe.

The large number of class I histocompatibility genes (HLA) and their extensive homology has made it difficult to assign bands on genomic Southern blots to known genes. Therefore, we have tried to obtain nucleic acid probes for class I genes that are locus specific or have restricted locus specificity. Computer sequence-homology analysis was used to compare the nucleic acid sequences of two genomic clones, one coding for the HLA-B7 antigen (JY150) and one containing a class I pseudogene (pHLA12.4). A sequence in the 3' untranslated region with very low homology was identified. This sequence from the HLA-B7 gene was subcloned into M13 phage. This fragment, JY150/C5, hybridized with two genomic bands in DNA from human HLA homozygotes--presumably the HLA-B locus gene and a closely related gene. The probe was used to assess restriction fragment polymorphism at the HLA-B locus in homozygous consanguineous cell lines. This analysis permitted the association of certain polymorphic restriction enzyme fragments with some alleles of this locus. However, many HLA-B alleles have identical restriction fragments produced by a number of restriction endonucleases.

Alleles↗
PubMed1985

Structure and polymorphism of murine and human class II major histocompatibility antigens.

The molecular analysis of the Class II region of the MHC of mice and of humans has to date led to some important conclusions. These regions encode sizeable families of related loci, at least 2 alpha and 6 beta in mice and 6 alpha and 7 beta in man. In addition to the sizeable number of potential molecules that could be expressed by the loci of this region, all the beta chains and both A alpha and DC alpha have extensive amounts of polymorphism. This polymorphism is strikingly similar at Class II loci in mouse and man. The majority of the variability is found in the first domain and consists of discrete regions of variability. These variable regions appear to be important functionally in presenting antigen, as evidenced by the bm12 mutant. The allotypy of these molecules is complex and is presumably generated by a combination of gene conversion and point mutation followed by selection. Final definition of the range of allelic variability and further insights into the mechanism by which it was generated are still to be resolved, as in a complete map of all the Class II loci in both mouse and man. The data available at present pose certain questions that now need to be addressed. The precise functional role of individual regions or residues of the Class II molecules can now be analyzed using the available sequence data and site specific mutagenesis. Fine structural analysis of these molecules is impossible at present using only sequence data, and X-ray crystallography will be required to answer fundamental questions about 3-dimensional structure. Finally, disease-specific sequences may be uncovered on particular haplotypes which permit the production of disease-specific probes. The molecular revelations of the last few years have resolved many questions about the polymorphisms of Class II products, but many new questions need to be resolved before these molecules and their extensive polymorphism can be properly understood.

Animals↗