CHARACTERIZATION OF VARIATION OF RECOMBINATION IN THE HUMAN MHC

人类主要组织相容性中重组的特征 复合体(MHC)可能会导致对功能 单倍型多样化的意义。此前，我们确定了 27个人类白细胞抗原II类重组家系的交叉位点分布 使用127个分布在II类中的新的多态标记 区域。重组主要发生在三个区域： 45kb--人类白细胞抗原DNA和RING3之间的间隔，即50kb的间隔 DQB3和DQB1之间，以及TAP2基因的8.8kb片段。我们有 现在开始用单个精子鉴定人类白细胞抗原重组染色体 用于测量重组变异性的分型方法 个体之间的频率和位置。单个精子的单倍体DNA 使用随机寡核苷酸引物进行扩增，产物为 在MHC两侧的两个微卫星标记上打字。初赛 Screen已经鉴定了2136个分型精子的49条重组染色体 (2.29%)来自捐赠者A，1705人中有20人(1.58%)来自捐赠者B 个体之间的频率差异很大。 重组发生在第III类(0.57%比0.08%)和第I类 (0.77%对0.31%)区域，以及全部4个百万对区域 包括MHC(2.97%对1.58%)。进一步的研究将是 有必要确定这些差异是否是单倍型驱动的。

Characterization of recombination in the human major histocompatibility complex (MHC) may lead to an understanding of the functional significance of haplotype diversification. Previously, we determined the distribution of crossover sites in 27 HLA class II recombinant families using 127 novel polymorphic markers located throughout the class II region. Recombination was shown to occur primarily in three regions: the 45 kilobase (kb)-interval between HLA-DNA and RING3, the 50-kb interval between DQB3 and DQB1, and an 8.8-kb segment of the TAP2 gene. We have now begun to identify HLA recombinant chromosomes using single sperm typing methods in order to measure variability of recombination frequency and location among individuals. Haploid DNA from single sperm is amplified using random oligonuclotide primers, and the products are typed at two microsatellite markers flanking the MHC. A preliminary screen has identified 49 recombinant chromosomes of 2,136 sperm typed (2.29%) from donor A and 20 of 1,705 (1.58%) from donor B. These two individuals differed significantly in the frequency at which recombination occurred in the class III (0.57% vs. 0.08%) and class I (0.77% vs. 0.31%) regions, as well as the entire 4 mebabase- pair region encompassing the MHC (2.97% vs. 1.58%). Further studies will be necessary to determine whether these differences are haplotype driven.