Chromosome 7 long arm deletion in myeloid disorders: a narrow breakpoint region in 7q22 defined by molecular mapping.-猫眼课题宝

骨髓疾病中的 7 号染色体长臂缺失：分子作图定义的 7q22 中狭窄的断点区域。

DOI：

发表时间：

1989

期刊：

Blood

影响因子：

20.3

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

J. Kere;T. Ruutu;K. Davies;I. Roninson;P. Watkins;R. Winqvist;A. Delachapelle

在患有或不患有 7 号染色体异常的骨髓疾病患者中，研究了位于染色体 7q21-22 区域的促红细胞生成素 (EPO)、I 型纤溶酶原激活剂抑制剂 (PAI1) 和多药耐药 (MDR2) 基因的参与情况。使用基因特异性 DNA 探针对 21 名患者分离的血液单核细胞和粒细胞进行限制性片段长度多态性 (RFLP) 研究。在 7 号单体杂合患者的粒细胞来源 DNA 中观察到其中一条等位基因带明显减弱。在 4 名 7 号染色体长臂 (7q-) 部分缺失的患者中，用 PAI1 探针（4 名杂合患者）和 MDR2 探针（1 名杂合患者）在粒细胞来源 DNA 中观察到等位基因带明显减弱，这意味着这些基因被删除。相比之下，这些患者的 EPO 基因并未被删除，粒细胞衍生 DNA 中存在两个强度相等的等位基因带（两名患者）或基因剂量估计（两名患者）证明了这一点。使用位于 7cen-q21.3 的任意探针 (pKV13)，还在三名杂合患者中观察到两个等强度的等位基因带。在任何患者中均未观察到意外的半合性或杂交带。我们得出结论，PAI1 和 MDR2 位于 7q22 中 EPO 的远端，并且这些基因在骨髓疾病中通常不会重排。不同患者的7号染色体长臂缺失断点位于PAI1和EPO基因之间相对狭窄的片段。缺失可能涉及DNA中的特定位点，因为PAI1和EPO基因之间的遗传距离仅为3 cM。

The involvement of the erythropoietin (EPO), plasminogen activator inhibitor type I (PAI1), and multi-drug resistance (MDR2) genes located in chromosomal region 7q21-22 was studied in patients with myeloid disorders and with or without a chromosome 7 abnormality. Separated blood mononuclear cells and granulocytes from 21 patients were used in restriction fragment length polymorphism (RFLP) studies with gene-specific DNA probes. A marked weakness of one of the allelic bands was observed in granulocyte-derived DNA from heterozygous patients with monosomy 7. In four patients with a partial deletion of chromosome 7 long arm (7q-), marked weakness of an allelic band was observed in granulocyte-derived DNA with PAI1 probe (four heterozygous patients) and MDR2 probe (one heterozygous patient), implying deletion of these genes. In contrast, the EPO gene was not deleted in these patients, as demonstrated by the presence of two allelic bands of equal strength in granulocyte-derived DNA (two patients) or by gene dosage estimation (two patients). Two allelic bands of equal strength were also observed in three heterozygous patients with an arbitrary probe (pKV13) located in 7cen-q21.3. Unexpected hemizygosity or hybridization bands were not observed in any patient. We conclude that PAI1 and MDR2 are located distally of EPO in 7q22, and that none of these genes is commonly rearranged in myeloid disorders. The chromosome 7 long arm deletion breakpoint is located in a relatively narrow segment between the PAI1 and EPO genes in different patients. The deletion may involve a specific site in DNA, since the genetic distance between the PAI1 and EPO genes is only 3 cM.