Precise localization of NF1 to 17q11.2 by balanced translocation.
Precise localization of NF1 to 17q11.2 by balanced translocation.
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DOI：
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发表时间：
1989
影响因子：
9.8
通讯作者：
D. Ledbetter;D. C. Rich;Peter O'Connell;M. Leppert;John C. Carey
中科院分区：
文献类型：
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作者：
D. Ledbetter;D. C. Rich;Peter O'Connell;M. Leppert;John C. Carey
一名女性患者患有 von Recklinghausen 神经纤维瘤病 (NF1)，与 17 号和 22 号染色体之间的平衡易位有关 [46,XX,t(17;22)(q11.2;q11.2)]。 17 号染色体上的断点在细胞遗传学上与先前报道的与 1;17 平衡易位相关的 NF1 病例相同，表明易位事件破坏了 NF1 基因。这将 NF1 基因精确地映射到 17q11.2，并为克隆断点和克隆 NF1 基因的策略提供了物理参考点。人-小鼠体细胞杂交体由患者淋巴母细胞构建，保留了衍生的 22 号染色体 (22pter----22q11.2::17q11.2----17qter)，但不保留衍生的 17q 或正常 17。对已知位于近端 17q 的基因和匿名探针进行的 Southern 印迹分析显示，杂交体中存在 ErbA1、ErbB2 和粒细胞集落刺激因子 (CSF3)因此位于断点的远端，而杂交体中不存在 pHHH202 (D17S33) 和 β 晶状体蛋白 (CRYB1)，因此位于断点的近端。已知包括 ErbA1 在内的基因簇两侧是杂种 SP3 中的组成性 15;17 易位断点和急性早幼粒细胞白血病 (APL) 断点，其提供以下基因和断点顺序：cen-SP3-(D17S33,CRYB1)-NF1-(CSF3,ERBA1, ERBB2)-APL-tel。因此，SP3 和 API 的侧翼断点可用于将新标记快速定位到神经纤维瘤病关键区域，而两个易位患者的断点为克隆 NF1 基因的反向遗传策略提供了独特的机会。
A female patient is described with von Recklinghausen neurofibromatosis (NF1) in association with a balanced translocation between chromosome 17 and 22 [46,XX,t(17;22)(q11.2;q11.2)]. The breakpoint in chromosome 17 is cytogenetically identical to a previously reported case of NF1 associated with a 1;17 balanced translocation and suggests that the translocation events disrupt the NF1 gene. This precisely maps the NF1 gene to 17q11.2 and provides a physical reference point for strategies to clone the breakpoint and therefore the NF1 gene. A human-mouse somatic cell hybrid was constructed from patient lymphoblasts which retained the derivative chromosome 22 (22pter----22q11.2::17q11.2----17qter) but not the derivative 17q or normal 17. Southern blot analysis with genes and anonymous probes known to be in proximal 17q showed ErbA1, ErbB2, and granulocyte colony-stimulating factor (CSF3) to be present in the hybrid and therefore distal to the breakpoint, while pHHH202 (D17S33) and beta crystallin (CRYB1) were absent in the hybrid and therefore proximal to the breakpoint. The gene cluster including ErbA1 is known to be flanked by the constitutional 15;17 translocation breakpoint in hybrid SP3 and by the acute promyelocytic leukemia (APL) breakpoint, which provides the following gene and breakpoint order: cen-SP3-(D17S33,CRYB1)-NF1-(CSF3,ERBA1, ERBB2)-APL-tel. The flanking breakpoints of SP3 and API are therefore useful for rapidly localizing new markers to the neurofibromatosis critical region, while the breakpoints of the two translocation patients provide unique opportunities for reverse genetic strategies to clone the NF1 gene.