2 INFLAMMATORY MEDIATOR CYTOKINE GENES ARE CLOSELY LINKED AND VARIABLY AMPLIFIED ON CHROMOSOME-17Q
2 INFLAMMATORY MEDIATOR CYTOKINE GENES ARE CLOSELY LINKED AND VARIABLY AMPLIFIED ON CHROMOSOME-17Q
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DOI：
10.1093/nar/18.11.3261
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发表时间：
1990-06-11
影响因子：
14.9
通讯作者：
KELLY, K
中科院分区：
文献类型：
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作者：
IRVING, SG;ZIPFEL, PF;KELLY, K
静息T细胞的促有丝分裂刺激导致大量基因的从头转录，包括那些编码调节分子如淋巴因子的基因。两个新描述的诱导淋巴因子基因，464.1和744.1的基因组组织已被确定。464.1和744.1似乎是最近克隆的鼠巨噬细胞炎性蛋白MIP-1 α的人同源物。和MIP-1 β，分别464.1和744.1基因共享55%的氨基酸同源性，并证明在T细胞中诱导表达的平行调节。因此，有趣的是观察到这些基因在人类基因组中紧密相连，相隔14 kb，并且以头对头的方式组织。每个基因都存在于额外的非等位基因拷贝（称为462.2和744.2）中，作为许多个体基因组中表观扩增单元的一部分。464.2基因被表达，并可能编码与464.1高度相关的蛋白质，92个氨基酸中有5个不同。正如预期的那样，464.2和744.2也彼此紧密连锁，这是由群体连锁不平衡研究确定的。携带第三个扩增事件的染色体的个体，涉及464相关基因而不是744相关基因，也很少观察到。这些基因都位于17号染色体上的q11-q21带中，该区域与von Recklinghausen神经纤维瘤病（NF 1）和急性早幼粒细胞白血病（AML-M3）有关。
Mitogenic stimulation of resting T cells results in the de novo transcription of a large number of genes including those encoding regulatory molecules such as lymphokines. The genomic organization of two newly described induced lymphokine genes, 464.1 and 744.1, has been determined. 464.1 and 744.1 appear to be the human homologues of the recently cloned murine macrophage inflammatory proteins, MIP-1.alpha. and MIP-1.beta., respectively. The 464.1 and 744.1 genes share 55% amino acid homology and demonstrate parallel regulation of induced expression in T cells. It was therefore of interest to observe that these genes are closely linked in the human genome, separated by 14 kb, and are organized in a head to head fashion. Each of the genes is present in an additional nonallelic copy (referred to as 462.2 and 744.2) as part of an apparent amplification unit in the genome of many individuals. The 464.2 gene is expressed and potentially encodes a protein highly related to 464.1, varying in 5 of 92 amino acids. As expected, 464.2 and 744.2 are also closely linked to each other as determined by population linkage disequilibrium studies. Individuals bearing a chromosome with a third amplification event, involving a 464-related gene but not a 744-related gene, are also infrequently observed. These genes are all located on chromosome 17 in bands q11-q21, the region implicated in von Recklinghausen neurofibromatosis (NF1) and in acute promyelocytic leukemia (AML-M3).