Laurent Anne-Marie, Li Meizhang, Sherman Stephanie, Roizès Gérard, Buard Jérôme
Institut de Génétique Humaine, 141 rue de la Cardonille, 34396 Montpellier cedex 5, France.
Hum Mol Genet. 2003 Sep 1;12(17):2229-39. doi: 10.1093/hmg/ddg220. Epub 2003 Jul 8.
Meiotic recombination is generally suppressed across the centromere of eukaryotic chromosomes. In human, megabase-long satellite sequences and contiguous segmental duplications hamper both physical and fine scale genetic mapping in regions flanking centromeric DNA. We have developed polymorphic microsatellite markers embedded within the duplicated most proximal sequences of the long arm and of the short arm of chromosome 21 by using paralogous specific bases as anchor points for their specific detection. Segregation analysis in CEPH reference pedigrees shows that recombination is repressed significantly across the centromere of chromosome 21 both in male and in female but not in the most proximal 21q region in female. Extreme size variations of the alpha-satellite I blocks transmitted in these families and deduced from quantitative FISH analysis are not correlated with the inter-individual variations of recombination activity observed in the peri-centromeric region. Finally, none of 28 families with a trisomy 21 child previously associated with a nullitransitional meiosis I non-disjunction event presents a recombination exchange across the centromere. This confirms that, for this group of errors, the lack of recombination is the primary susceptibility factor, not abnormal recombination in the centromeric region.
减数分裂重组通常在真核染色体的着丝粒区域受到抑制。在人类中，长达兆碱基的卫星序列和连续的节段性重复阻碍了着丝粒DNA侧翼区域的物理图谱绘制和精细尺度的遗传图谱绘制。我们利用旁系同源特异性碱基作为特异性检测的锚定点，开发了嵌入在21号染色体长臂和短臂重复的最近端序列中的多态微卫星标记。在CEPH参考家系中的分离分析表明，21号染色体着丝粒区域的重组在男性和女性中均受到显著抑制，但在女性中最近端的21q区域则不然。在这些家系中传递的α-卫星I块的极端大小变异，以及通过定量FISH分析推断出的变异，与在着丝粒周围区域观察到的个体间重组活性变异无关。最后，在先前与减数分裂I零转换不分离事件相关的28个有21三体患儿的家系中，没有一个家系在着丝粒区域发生重组交换。这证实了，对于这组错误而言，缺乏重组是主要的易感因素，而非着丝粒区域的异常重组。
