Six new DR52-associated DRB1 alleles, three of DR8, two of DR11, and one of DR6, reflect a variety of mechanisms which generate polymorphism in the MHC.
We have sequenced DNA from six new DR52-associated DRB1 alleles initially detected by PCR/SSOP analysis. Three DR8 associated alleles differed from previously known alleles by single nucleotide substitutions. DRB1*0807 and DRB1*0811 both vary from DRB1*08021 at codon 57 resulting in two different amino acids at this residue. DRB1*0807 was identified in samples of Brazilian origin while *0811 was identified among samples from the Tlingit Native American population of Southeast Alaska. DRB1*0814, identified in a family of Chinese origin, differed from DRB1*08032 at codon 12 at both the nucleotide and the amino acid level. In addition, two alleles of DR11, DRB1*1113 and *1119, were each detected in Caucasian individuals. DRB1*1113 differs from other DR11 alleles at codons 37, 67, 70 and 74, while DRB1*1119 differs from *1101 by a single nucleotide substitution at codon 67. Finally, DRB1*1418 was detected in a sample from an Asian or Pacific Islander and shares sequences with several other DR52-associated DRB1 alleles. These six DRB1 alleles appear to have been generated by either gene conversion events, DRB1*1113 and *1418, or by point mutations, DRB1*0814, *0807, *0811 and *1119, although the single nucleotide substitutions found in the latter three alleles are also present in at least one other DRB1 allele and, therefore, could have been the product of gene conversions.
Smith
A G
AG
Human Immunogenetics Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Nelson
J L
JL
Regen
L
L
Guthrie
L A
LA
Donadi
E
E
Mickelson
E M
EM
Hansen
J A
JA
D001483:Base Sequence; D008040:Genetic Linkage / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D015808:HLA-DR6 Antigen / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000276:immunology*
D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D015808:HLA-DR6 Antigen; C041559:HLA-DR8 antigen; D059811:HLA-DRB1 Chains