Haplotype associations of 90 rare alleles from the National Marrow Donor Program®^®

Abstract

The National Marrow Donor Program maintains an HLA database of over 4.1 million US adult volunteers, 43,000 cord blood units, and 111,000 patients from which we identified 1,999,424 samples having allele-level HLA-A, HLA-B, or HLA-DRB1 results. We analyzed 811 rare alleles reported at a frequency of less than 1 in 50,000 in this study pool and found strong predicted haplotype associations for 90 of them. The data set includes the number of times the allele was seen, the predicted haplotypes, and the racial or ethnic groups in which it was identified. This information can be helpful in designing search strategies for patients with rare alleles requiring hematopoietic stem cell therapy.

Estimation of human leukocyte antigen class I and class II high-resolution allele and haplotype frequencies in the Italian population and comparison with other European populations

“…Reports on strong adverse effects of HLA mismatch at high-resolution levels on transplantation outcome re-emphasize that the selection of optimal unrelated donor should be based on allele matching [2][3][4]. Furthermore, matching at the haplotype level has a better likelihood of matching at other loci within the HLA region than for donors merely matched at the individual allelic level [5].…”

Human leukocyte antigen-A, -B, and -DRB1 haplotypes of cord blood units in the Tzu Chi Taiwan Cord Blood Bank

“…HLA matching at the haplotype level may have a higher likelihood of matching at other loci within the HLA region than matching merely at the allele level. Further, haplotype information may be utilized to consider a mismatched strategy for patients with rare alleles in which the probability of locating a matched, unrelated donor is less likely [1]. Hence, the distribution of HLA alleles and haplotypes in different ethnic populations is beneficial for finding an acceptable unrelated donor for a patient.…”

High-resolution human leukocyte antigen (HLA) haplotypes and linkage disequilibrium of HLA-B and -C and HLA-DRB1 and -DQB1 alleles in a Taiwanese population

“…HLA allele and haplotype frequencies are important in unrelated hematopoietic stem cell transplantation, in optimizing plans for donor recruitment, and in strategic considerations for minor mismatched donors when rare alleles are present in patients. Further, matching of unrelated stem cell transplantation between donors and recipients at the haplotype level has a better likelihood of matching at other loci within the HLA region than for donors merely matched at the individual allelic level [1]. Hence, haplotype determination is becoming important in transplantation medicine.…”

“…Hence, haplotype determination is becoming important in transplantation medicine. The determination of HLA haplotypes may be accomplished by HLA typing of bloodrelated family members [2] and prediction from a large-size population tissue typing [1,3,4]. Alternatively, it can be achieved by deducing typing results on donors with allelic homozygosities in the HLA-A, -B, and -DR loci [5].…”