The human CD38 gene:: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene
The human CD38 gene:: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene
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DOI：
10.1007/s002510050654
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发表时间：
1999-07-01
期刊：
影响因子：
3.2
通讯作者：
Malavasi, F
中科院分区：
文献类型：
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作者：
Ferrero, E;Saccucci, F;Malavasi, F
dCD38 是白细胞活化抗原和胞外酶 [NAD(P)(+) 糖水解酶； EC 3.2.2.6]参与多种免疫功能。人类 CD38 基因很复杂 [8 个外显子，>80 KB 长]，位于染色体 4p15 上，是真核 NAD(+) 糖水解酶/ADP-核糖基环化酶基因家族的一部分。由于 CD38 分子在宿主对传染病、肿瘤和代谢性疾病的免疫反应中的相关性越来越大，我们研究了人类 CD38 基因座的遗传变异和连锁。我们报道：(1) 限制性内切核酸酶 Pvu II 识别出双等位基因多态性，此处定义为由等位基因 CD38*A (12 kb) 和 CD38*B (9/2.5 kb) 形成； (2) 他们在健康的意大利白种人群体中的频率分别为 14% 和 86%； (3)多态性Pvu II位点位于CD38基因第一个内含子5'端； (4)结合多态性位点，我们鉴定了与CD38基因相关的一个900碱基对的CPG岛，具有两个潜在的Spl结合位点； (5) CpG岛可能在CD38表达调节中发挥作用，并且在多种细胞系中低甲基化； (6)通过脉冲场凝胶电泳我们发现，CD38及其旁系同源物骨髓基质细胞抗原BST-I (CD157)定位到相同的800 kb Avi II片段，表明这两个人外切NADase基因紧密相连。
dCD38 is a leukocyte activation antigen and ectoenzyme [NAD(P)(+) glycohydrolase; EC 3.2.2.6] involved in numerous immune functions. The human CD38 gene is complex [eight exons, >80 kilobases (kb) long] located on Chromosome 4p15, and part of the eukaryotic NAD(+) glycohydrolase/ADP-ribosyl cyclase gene family. Because of the increasing relevance of the CD38 molecule in the host immune response to infectious, tumoral, and metabolic diseases, we investigated the genetic variability and linkage of the human CD38 locus. We report that (1) the restriction endonuclease Pvu II identifies a bi-allelic polymorphism here defined as formed by the alleles CD38*A (12 kb) and CD38*B (9/2.5 kb); (2) their frequency in the healthy Italian Caucasian population is 14% and 86%, respectively; (3) the polymorphic Pvu II site is located at the 5' end of the first intron of the CD38 gene; (4) in conjunction with the polymorphic site, we identified a 900 base pair CPG island associated with the CD38 gene, with two potential Spl binding sites; (5) the CpG island may play a role in the regulation of CD38 expression and is hypomethylated in various cell lines; (6) by pulsed-field gel electrophoresis we show that,CD38 and its paralogue, the bone-marrow stromal cell antigen BST-I (CD157), map to the same 800 kb Avi II fragment, indieating that the two human ecto-NADase genes are closely linked.