Todd R, Bia B, Johnson E, Jones C, Cotter F
Molecular Haematology Unit, Institute of Child Health, University College, London, UK.
Br J Haematol. 2001 Apr;113(1):143-52. doi: 10.1046/j.1365-2141.2001.02713.x.
Chromosome 7 abnormalities are observed in a wide range of myeloid disorders, particularly myelodysplasia (MDS) and acute myeloid leukaemia (AML). Monosomy 7 and 7q deletions are the most frequent abnormalities, although translocations and inversions involving 7q also occur. The region 7q22--q34 may contain as many as four distinct minimal regions of deletion (MDRs), which are thought to contain one or more myeloid tumour-suppressor genes. We have defined previously the proximal breakpoint of a constitutional 7q22--q34 inversion, carried in a cell line derived from a member of a family with a history of MDS. A YAC clone spanning this breakpoint was identified. Both inversion breakpoints have now been cloned and sequenced, placing the proximal breakpoint 40 kb centromeric to the TAC2 (tachykinin 2) gene and the distal breakpoint 42 kb telomeric to the SSBP (mitochondrial single-stranded DNA-binding protein) gene. Sequence alignments revealed small (3--4 bp) duplications at the inversion breakpoints, suggesting that the mechanism of inversion involved the creation of staggered breaks and filling in of the overhanging ends. A 190-bp Alu--Alu deletion close to the distal breakpoint was also detected and may have contributed to the inversion.
在多种髓系疾病中均观察到7号染色体异常，尤其是骨髓增生异常综合征（MDS）和急性髓系白血病（AML）。7号染色体单体和7q缺失是最常见的异常情况，不过涉及7q的易位和倒位也会出现。7q22 - q34区域可能包含多达四个不同的最小缺失区域（MDR），人们认为这些区域含有一个或多个髓系肿瘤抑制基因。我们之前已确定了一个遗传性7q22 - q34倒位的近端断点，该倒位存在于一个来自有MDS病史家族成员的细胞系中。鉴定出了一个跨越此断点的酵母人工染色体（YAC）克隆。现在两个倒位断点均已克隆并测序，近端断点位于TAC2（速激肽2）基因着丝粒侧40 kb处，远端断点位于SSBP（线粒体单链DNA结合蛋白）基因端粒侧42 kb处。序列比对显示在倒位断点处有小的（3 - 4 bp）重复，这表明倒位机制涉及交错断裂的产生以及悬垂末端的填补。在靠近远端断点处还检测到一个190 bp的Alu - Alu缺失，它可能对倒位有影响。
