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Sequence analysis of two novelHLA-DMAalleles

✍ Scribed by Mary Carrington; Anita Harding


Book ID
104656155
Publisher
Springer-Verlag
Year
1994
Tongue
English
Weight
101 KB
Volume
40
Category
Article
ISSN
0093-7711

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✦ Synopsis


Several novel genes have been mapped recently in the HLA class II region between DQ and DP. Two of these genes, DMA and DMB, are predicted to encode a protein which has a structure similar to that of the DR, DQ, and DP molecules (Kelly et al. 199l). The function of the DM molecule, however, is unlikely to mimic precisely that of the other class II molecules, since they share a low level of similarity and both DMA and DMB have limited polymorphism (Carrington et al. 1993; Sanderson et al. 1994). Based on sequences from the third exon, four alleles of DMB, DMB*OI01, "0102, "0103, and "0104, and two alleles of DMA, DMA*OI01 and "0102 were characterized previously. Single-strand conformation polymorphism (SSCP) patterns of amplified DMA exon 3 products indicated the existence of two additional DMA alleles, DMA*OI03 and "0104, which were subsequently sequenced and are now reported here (Fig. ). Primers used in amplification of exon 3 of DMA for both sequencing and SSCP were as follows: 5'GGG TTT CCT ATC GCT GAA GTG 3' and 5'CCA ATA GGC AAT TGC TGT GTA 3'. The DMA alleles are defined by variants at four nucleotide positions involving codons 140, 155, and 184, all of which result in nonsynonymous amino acid changes (Fig. ). The frequencies of DMA alleles were determined by using DNA from 90 unrelated Centre d'Etude du Polymophisme Humain (CEPH; Paris, France) individuals (Fig. ), and the data supported the unbalanced distribution of alleles reported previously (Sanderson et al. 1994). Heterozygosity of 29% was observed. It is plausible that DMA*0102 and "0103 were derived directly from "0101 by single and double point mutations, respectively, and that "0104 was derived from the second most frequent allele, "0102, by single point mutation.


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Analysis of a Japanese population by oligonucleotide genotyping revealed that one Japanese HLA-DRw14 allele had a DRB1 genotype different from that of the known HLA-DRw14-related alleles, DRB1\*1401 (DRw14-Dw9) and DRB1\*1402 (DRw14-Dw16). The second exon of the DRB1 gene of the novel DRw14 allele (