Kauppi Liisa, Jasin Maria, Keeney Scott
Molecular Biology and Developmental Biology Programs, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13396-401. doi: 10.1073/pnas.0701965104. Epub 2007 Aug 9.
Fertility requires successful chromosome segregation in meiosis, which in most sexual organisms depends on the formation of appropriately placed crossovers. The nonrandom genome-wide distributions of meiotic recombination events have been examined at the molecular level experimentally in yeast and by inference from linkage disequilibrium patterns in humans. Thus far, no method has existed for pinpointing sites of crossing-over on a genome-wide scale in an experimentally tractable animal whose genome size and complexity models that of humans. Here, we present a genomic approach to identify mouse crossover hotspots, based on targeting haplotype block boundaries. This represents a previously undescribed method potentially applicable to large-scale mouse hotspot identification. Using this method, we have successfully predicted the location of two previously uncharacterized crossover hotspots in male mice. As increasing amounts of single-nucleotide polymorphism data emerge, this approach will be useful for investigating the recombination landscape of the mouse genome.
生育能力需要减数分裂过程中染色体的成功分离,在大多数有性生物中,这依赖于适当位置交叉的形成。减数分裂重组事件在全基因组范围内的非随机分布已在酵母中通过实验在分子水平上进行了研究,并通过人类连锁不平衡模式进行了推断。到目前为止,还没有一种方法可以在基因组规模上精确确定一种实验上易于处理的动物的交叉位点,这种动物的基因组大小和复杂性与人类相似。在这里,我们提出了一种基于靶向单倍型块边界来识别小鼠交叉热点的基因组方法。这代表了一种以前未描述的方法,可能适用于大规模小鼠热点识别。使用这种方法,我们成功地预测了雄性小鼠中两个以前未表征的交叉热点的位置。随着越来越多的单核苷酸多态性数据出现,这种方法将有助于研究小鼠基因组的重组图谱。