Male mouse recombination maps for each autosome identified by chromosome painting
Male mouse recombination maps for each autosome identified by chromosome painting
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DOI：
10.1086/344714
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发表时间：
2002-12-01
影响因子：
9.8
通讯作者：
Ashley, T
中科院分区：
文献类型：
--
作者：
Froenicke, L;Anderson, LK;Ashley, T
通过基因顺序和交叉频率的遗传分析构建的连锁图谱对减数分裂重组的全基因组分布基础提供的线索很少，例如染色体结构对减数分裂重组的影响。为了弥补这一差距，我们已经生成了第一个细胞学重组图，用于识别雄性小鼠中的单个常染色体。我们从110个小鼠精母细胞中制备了减数分裂染色体（突触复合体[SC]），通过染色体特异性DNA文库的多色荧光原位杂交鉴定每个常染色体，并利用标记交叉位点的错配修复蛋白MLH1的免疫定位，绘制了沿单个常染色体的12,000个重组位点。我们发现SC长度与交叉频率和分布密切相关。虽然大多数SCs的长度与有丝分裂染色体长度排序预测的长度一致，但也有一些SCs比预期的更长或更短，MLH1频率相应增加或减少。虽然所有的二价体都具有某些普遍的重组特征，如着丝粒附近的交叉很少，远端重组率高，但单个二价体在其长度上具有独特的交叉分布模式。除了SC长度外，其他尚未确定的因素影响交叉分布，导致单个染色体上出现重组频率高达平均水平6倍的热点区域，以及没有重组的冷点。通过用遗传标记的bac重新研究SC的传播，我们展示了一种将遗传连锁和物理组合图与有丝分裂和减数分裂染色体结构整合在一起的强大策略。
Linkage maps constructed from genetic analysis of gene order and crossover frequency provide few clues to the basis of genomewide distribution of meiotic recombination, such as chromosome structure, that influences meiotic recombination. To bridge this gap, we have generated the first cytological recombination map that identifies individual autosomes in the male mouse. We prepared meiotic chromosome (synaptonemal complex [SC]) spreads from 110 mouse spermatocytes, identified each autosome by multicolor fluorescence in situ hybridization of chromosome-specific DNA libraries, and mapped 1 2,000 sites of recombination along individual autosomes, using immunolocalization of MLH1, a mismatch repair protein that marks crossover sites. We show that SC length is strongly correlated with crossover frequency and distribution. Although the length of most SCs corresponds to that predicted from their mitotic chromosome length rank, several SCs are longer or shorter than expected, with corresponding increases and decreases in MLH1 frequency. Although all bivalents share certain general recombination features, such as few crossovers near the centromeres and a high rate of distal recombination, individual bivalents have unique patterns of crossover distribution along their length. In addition to SC length, other, as-yet-unidentified, factors influence crossover distribution leading to hot regions on individual chromosomes, with recombination frequencies as much as six times higher than average, as well as cold spots with no recombination. By reprobing the SC spreads with genetically mapped BACs, we demonstrate a robust strategy for integrating genetic linkage and physical contig maps with mitotic and meiotic chromosome structure.