Molecular characterization of a recombinant HLA-DR1/DR2 haplotype.
Serologic analysis of two families identified an HLA-DR haplotype in which DR1 and DR2 cosegregated. DNA-RFLP analysis of these families with an HLA-DRB probe revealed a pattern of hybridization suggestive of a recombination between DR1 and DR15. Following amplification, cloning, and nucleotide sequencing of HLA-DRB-gene second-exon DNA sequences, three DRB amplification products associated with the novel haplotype were identified: these corresponded to DRB1*0101, DR2 pseudogene, and DRB5*0101. Clones representing the DRB1*1501 and DR1 pseudogenes were not identified: oligonucleotide typing with DRB1*1501-specific probes confirmed the absence of this gene within the DR1/DR2 haplotype. We postulate that the DR1/DR2 haplotype represents a recombinant between those of DR1-Dw1 and DR15-Dw2, and that the crossing-over may have been between the DRB1*0101 gene and the DR2 pseudogene. This is further supported by DNA-RFLP analysis with HLA-DQB and DQA CDNA probes, which revealed conserved linkage genes between the DQB1*0501, DQA1*0101, and DRB1*0101 genes.
UK Transplant Support Service, Bristol, England.
J L
JL
Bidwell
E A
EA
Bidwell
E
E
Dupont
M
M
Andrien
C
C
Bouillenne
P T
PT
Klouda
B A
BA
Bradley
D001483:Base Sequence; D008040:Genetic Linkage; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000235:genetics*; D015802:HLA-DR2 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011995:Recombination, Genetic
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015798:HLA-DR1 Antigen; D015802:HLA-DR2 Antigen; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II