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PMID: 3856276 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Characterization of an HLA DR beta pseudogene.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 82 ·No. 5 ·1985-03-00 ·Pages 1475-9

Larhammar D, Servenius B, Rask L, Peterson PA

Abstract

The class II molecules of the human major histocompatibility complex include the DR, DC, and SB antigens, each composed of an alpha and a beta polypeptide chain. We have isolated a DR beta gene in overlapping cosmid clones made from genomic DNA of a Dw4/DR4 homozygous individual. This gene consists of six exons and spans greater than 20 kilobases. Upon sequencing, it was found to possess several deleterious mutations, each capable of rendering the gene nonfunctional: (i) four splice junctions deviate from the G-T/A-G rule; (ii) two premature termination codons are present in the first domain exon; (iii) a 2-base-pair insertion causes a translational frame shift in the second domain exon. In addition, several amino acid residues that are conserved in all known expressed beta chains have been replaced in the amino acid sequence predicted from the pseudogene. Analysis of the pattern of nucleotide substitutions in the second domain exon suggests that most amino acid replacements occurred after the gene was inactivated. The inactivation may have been caused by insertion of a Kpn I repeat 5' to the promoter region, thereby interfering with transcription of the gene through removal of transcriptional enhancer elements. The DR beta pseudogene seems to be present also in other DR4 individuals.

MeSH Terms
Amino Acid Sequence Base Sequence Cloning, Molecular Genes HLA-DR Antigens Histocompatibility Antigens Class II/genetics Humans Mutation Polymorphism, Genetic Promoter Regions, Genetic
Chemicals
HLA-DR Antigens Histocompatibility Antigens Class II
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Larhammar D
Servenius B
Rask L
Peterson P A
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39 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.82.5.1475
Published
1985-03-00
Pages
1475-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC397285
Subset
IM
Databases
GENBANK
K02772, K02773, K02774
External Links
PubMed source DOI: 10.1073/pnas.82.5.1475 PMC Full Text View journal details
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