Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey.
Immunogenetics. 2012 Nov;64(11):839-44. doi: 10.1007/s00251-012-0644-y. Epub 2012 Aug 15.
We studied the rate and pattern of recombinations within the extended major histocompatibility complex (MHC) locus of the human embryos obtained during preimplantation genetic diagnosis (PGD) for HLA compatibility. Recombinant allele frequency was on average 5.33 %, and recombination rate was 0.44 cM/Mb in the 12.2 Mb of the extended MHC locus. Recombination rate varied up to 14-fold (0.19-2.73 cM/Mb) between cases, and maternal recombination rate was on average 3.8 times higher than paternal alleles. More than 69 % of the recombination hot spots were clustered within the extended class II region where the recombination rate was 5.4 times more than that in extended class I region. These findings indicate the potential of PGD to study the mechanisms of linkage disequilibrium within MHC locus of human embryos, demonstrate the recombination characteristics within extended MHC loci of human embryos in comparison to sperm and family studies, and point to the significance of design and interpretation of PGD for HLA compatibility to avoid misdiagnosis because of meiotic recombinations.
我们研究了人类胚胎在植入前遗传诊断（PGD）过程中为 HLA 相容性而进行的扩展主要组织相容性复合体（MHC）基因座内重组的速度和模式。重组等位基因频率平均为 5.33%，在 12.2Mb 的扩展 MHC 基因座中重组率为 0.44cM/Mb。重组率在病例之间变化高达 14 倍（0.19-2.73cM/Mb），并且母本重组率平均比父本等位基因高 3.8 倍。超过 69%的重组热点聚集在扩展 II 类区域内，该区域的重组率比扩展 I 类区域高 5.4 倍。这些发现表明 PGD 有潜力研究人类胚胎 MHC 基因座内连锁不平衡的机制，与精子和家族研究相比，展示了人类胚胎扩展 MHC 基因座内的重组特征，并指出了 HLA 相容性 PGD 的设计和解释的重要性，以避免由于减数分裂重组而导致的误诊。
