Parental chromosomal segregation and meiotic recombination account for variation in genome-wide recipient mismatching between siblings. (A) Differential inheritance of paternal and maternal chromosomes causes mismatching between sibling pairs. If a pair of paternal chromosomes is designated “a” and “b” and the respective pair of maternal chromosomes is designated “c” and “d,” the chromosomes inherited by the offspring in the absence of meiotic recombination will be “ac,” “bc,” “ad,” or “bd.” Inheritance of the same chromosome pairs by a sibling pair (eg, “ac”) as shown for siblings 1 and 2 is described as IBD with an identity by state (IBS) value of 2, indicating identity for both chromosomes. Inheritance of 1 identical chromosome and 1 nonidentical chromosome by a sibling pair (eg, “ac” and “ad”) is described as partial IBD with an IBS value of 1. Inheritance of 2 nonidentical chromosomes by a sibling pair (eg, “ac” and “bd”) is described as having an IBS value of 0. (B) Meiotic recombination introduces different IBS values across segments of chromosomes inherited by sibling pairs. The figure shows results for 3 sibling pairs with high (top), medium (middle), and low (bottom) genome-wide mismatching across chromosome 6, analyzed as described by Roberson and Pevsner.27 HLA-matching of these pairs is indicated by IBS values of 2 (green) across the MHC region. Genome-wide mismatching increases as the length of segments with IBS values of 2 decreases. Segments with IBS values of 0 (red) and 1 (blue) have different probabilities of recipient mismatching (see supplemental Appendix for details).
