SNP genotyping with the use of high-density DNA arrays shows the fine structure of donor-recipient genetic identity both within and outside the MHC. (A) Definition of the concept of donor/recipient genetic identity by state (IBS). The genotypes of a hypothetical HCT donor/recipient pair at 4 SNPs located in different intervals on chromosome 1 are indicated by the letters above the corresponding positions on the donor and recipient chromosomes; the IBS score between donor and recipient at each of the 4 SNPs (either 0, 1, or 2 alleles shared) is indicated at the bottom of the panel immediately below the position of each SNP. (B) Distribution of the average IBS across 14 098 SNPs, all with minor allele frequency ≥ 0.2, on chromosome 6 for 1378 HCT donor/recipient pairs who received a transplant at the Fred Hutchinson Cancer Research Center between 1992 and 2004; genotypes were determined with the Affymetrix Human SNP 5.0 chip.76 The transplant pairs were classified as matched related donor (MRD; n = 595), mismatched related donor (MMRD; n = 122), matched unrelated donor (MUD; n = 347), or mismatched unrelated (MMUD; n = 302) pairs based on their relationship to one another and on their degree of HLA matching, as determined by sequencing of their HLA-A, -B, -C, -DRB1, and -DQB1 alleles (matched, 10 of 10 alleles; mismatched, < 10 of 10 alleles). The distribution of average IBS across the same 14 098 SNPs between 661 randomly selected pairs of persons in the cohort and between replicate genotypes for 45 persons is also shown. (C) The haplotype-based IBS in a sliding window of 7 adjacent SNPs calculated for all 26 814 SNPs on chromosome 6 with < 10% missing genotypes is plotted for the MRD, MMRD, MUD, and MMUD donor/recipient pairs. The haplotype-based IBS in a window of SNPs is the statistical expectation of the number of haplotypes shared by the donor and recipient, given their unphased SNP genotypes within that interval. (D) Magnified view of the haplotype-based IBS data from panel C for all of the SNPs in a 10-Mb interval on chromosome 6p that spans the entire MHC. The location of the HLA-A, -C, -B, -DRB1, and -DQB1 genes is indicated by the dashed vertical red lines.
