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The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles.

Publication ,  Journal Article
Prasad, VK; Heller, G; Kernan, NA; O'Reilly, RJ; Yang, SY
Published in: Transplantation
October 15, 1999

BACKGROUND: Recent evidence suggests a more significant role of HLA-C as a target of alloreactions after bone marrow transplantation than previously suspected. Although linkage disequilibrium (LD) between HLA-B and -C serogroups is well documented, the level of LD at the allelic level is not known. In this study, we determine the LD between HLA-B and -C alleles and estimate the probability of molecular HLA-C matching between unrelated individuals who match for both HLA-B alleles. METHODS: The study included 727 haplotypes from 849 individuals who were HLA-A, -B, -C and -DRB1 typed by high-resolution PCR-SSOP technique. Zelterman's statistic was used to test for global LD between HLA loci. LD between specific HLA-B and -C allelic combinations was calculated from their observed and expected frequencies in the study haplotypes. The probability of HLA-C matching for specific HLA-B allele was estimated from contingency table generated from the HLA-B and -C haplotypes. RESULTS: HLA-C was found to exist in LD with HLA-A and -B, as well as -DRB1, loci; however, it was strongest between HLA-B and -C loci. A marked variability in the level of LD between specific HLA-B and -C alleles was noticed. A strong LD was seen in some allele pairs like B*0702-C*w0702, B*3501-Cw*0401, and B*0801-Cw*0701. The overall estimated probability of HLA-C matching between unrelated individuals that match for both HLA-B alleles is 42.25%. For 237 (72.9%) of 325 combinations involving the 25 commonest HLA-B alleles, the estimated probability that the HLA-B-matched unrelated individuals will match for both HLA-C alleles is less than 50%. In addition, a 100% probability of matching for both HLA-C alleles is expected only if both individuals bear either B*0801/ B*0801 or B*4901/B*4901 or B*0801/B*4901. Probability tables for common alleles are presented. CONCLUSIONS: We conclude that, despite matching for both HLA-B alleles by high resolution DNA typing and the presence of a strong LD between HLA-B and HLA-C loci, unrelated individuals are more likely to mismatch rather than match for one or both HLA-C alleles.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

October 15, 1999

Volume

68

Issue

7

Start / End Page

1044 / 1050

Location

United States

Related Subject Headings

  • Tissue Donors
  • Surgery
  • Probability
  • Polymerase Chain Reaction
  • Linkage Disequilibrium
  • Humans
  • Histocompatibility Testing
  • Haplotypes
  • HLA-C Antigens
  • HLA-B Antigens
 

Citation

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Prasad, V. K., Heller, G., Kernan, N. A., O’Reilly, R. J., & Yang, S. Y. (1999). The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles. Transplantation, 68(7), 1044–1050. https://doi.org/10.1097/00007890-199910150-00024
Prasad, V. K., G. Heller, N. A. Kernan, R. J. O’Reilly, and S. Y. Yang. “The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles.Transplantation 68, no. 7 (October 15, 1999): 1044–50. https://doi.org/10.1097/00007890-199910150-00024.
Prasad, V. K., et al. “The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles.Transplantation, vol. 68, no. 7, Oct. 1999, pp. 1044–50. Pubmed, doi:10.1097/00007890-199910150-00024.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

October 15, 1999

Volume

68

Issue

7

Start / End Page

1044 / 1050

Location

United States

Related Subject Headings

  • Tissue Donors
  • Surgery
  • Probability
  • Polymerase Chain Reaction
  • Linkage Disequilibrium
  • Humans
  • Histocompatibility Testing
  • Haplotypes
  • HLA-C Antigens
  • HLA-B Antigens