Mutational analysis of the HLA-DQ3. 2 insulin-dependent diabetes mellitus susceptibility gene

Journal Article · Wed Feb 01 00:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.3.1027· OSTI ID:7068402

Kwok, W W; Lotshaw, C; Milner, E C.B.; Knitter-Jack, N; Nepom, G T ^[1]

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1. Virginia Mason Research Center, Seattle, WA (USA)

The human major histocompatibility complex includes approximately 14 class II HLA genes within the HLA-D region, most of which exist in multiple allelic forms. One of these genes, the DQ3.2{beta} gene, accounts for the well-documented association of HLA-DR4 with insulin-dependent diabetes mellitus and is the single allele most highly correlated with this disease. The authors analyzed the amino acid substitutions that lead to the structural differences distinguishing DQ3.2{beta} from its nondiabetogenic, but closely related allele, DQ3.1{beta}. Site-directed mutagenesis of the DQ3.2{beta} gene was used to convert key nucleotides into DQ3.2{beta} codons. Subsequent expression studies of these mutated DQ3.2{beta} clones using retroviral vectors defined amino acid 45 as critical for generating serologic epitopes characterizing the DQw3.1{beta} and DQw3.2{beta} molecules.

• OSTI ID: 7068402
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:3; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DIABETES MELLITUS
GENETICS
GENES
MUTAGENESIS
HISTOCOMPATIBILITY COMPLEX
AMINO ACID SEQUENCE
CELL FLOW SYSTEMS
DNA HYBRIDIZATION
FLUORESCENCE
HEREDITARY DISEASES
OLIGONUCLEOTIDES
ANTIGENS
BIOLOGY
DISEASES
ENDOCRINE DISEASES
HYBRIDIZATION
LUMINESCENCE
METABOLIC DISEASES
MOLECULAR STRUCTURE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
550401* - Genetics- Tracer Techniques