Harteveld K L, Losekoot M, Fodde R, Giordano P C, Bernini L F
MGC Department of Human Genetics, Leiden University, The Netherlands.
Hum Genet. 1997 Apr;99(4):528-34. doi: 10.1007/s004390050401.
Alu repetitive sequences are frequently involved in homologous and non-homologous recombination events in the alpha-cluster. Possible mechanisms involved in Alu-mediated recombination events are strand exchange, promoted by DNA pairing between highly homologous Alu repeats, and subsequent strand invasion. Alternatively, Alu sequences might play a more active role in recombinogenic processes in the alpha-cluster. We describe a novel 33-kb alphazero-thalassaemia deletion --DUTCH encompassing the alpha- and zeta-globin genes and pseudogenes in a kindred of Dutch-Caucasian origin. This deletion appears similar, although not identical, to the previously described --MEDII deletion. Cloning and sequencing of both the --DUTCH and --MEDII deletion breakpoints clearly indicate that the mechanism leading to these alphazero-thalassaemia deletions involves misalignment between the highly homologous tandemly arranged Alu repeats at both parental sides, which are normally 33 kb apart. Comparison of breakpoint positions along the Alu consensus sequence indicate the involvement of a 26-bp core sequence in two out of five alphazero-thalassaemia deletions. This sequence has been identified by others as a possible hotspot of recombination. These findings favour the idea that Alu repeats stimulate recombination events not only by homologous pairing, but also by providing binding sites for recombinogenic proteins.
Alu重复序列经常参与α基因簇中的同源和非同源重组事件。Alu介导的重组事件可能涉及的机制是由高度同源的Alu重复序列之间的DNA配对促进的链交换，以及随后的链侵入。另外，Alu序列可能在α基因簇的重组过程中发挥更积极的作用。我们描述了一种新的33kb的α0地中海贫血缺失——DUTCH，它包含了一个荷兰-高加索血统家族中的α和ζ珠蛋白基因及假基因。这种缺失虽然与先前描述的——MEDII缺失并不完全相同，但看起来相似。对——DUTCH和——MEDII缺失断点的克隆和测序清楚地表明，导致这些α0地中海贫血缺失的机制涉及双亲两侧高度同源的串联排列的Alu重复序列之间的错配，这些重复序列通常相隔33kb。沿Alu共有序列的断点位置比较表明，在五分之二的α0地中海贫血缺失中，一个26bp的核心序列参与其中。该序列已被其他人鉴定为可能的重组热点。这些发现支持了这样一种观点，即Alu重复序列不仅通过同源配对刺激重组事件，还通过为重组蛋白提供结合位点来刺激重组事件。
