HUMAN DELTA-AMINOLEVULINATE SYNTHASE - ASSIGNMENT OF THE HOUSEKEEPING GENE TO 3P21 AND THE ERYTHROID-SPECIFIC GENE TO THE X-CHROMOSOME
HUMAN DELTA-AMINOLEVULINATE SYNTHASE - ASSIGNMENT OF THE HOUSEKEEPING GENE TO 3P21 AND THE ERYTHROID-SPECIFIC GENE TO THE X-CHROMOSOME
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DOI：
10.1016/0888-7543(90)90542-3
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发表时间：
1990-06-01
期刊：
影响因子：
4.4
通讯作者：
ASTRIN, KH
中科院分区：
文献类型：
--
作者：
BISHOP, DF;HENDERSON, AS;ASTRIN, KH
δ-氨基乙酰丙酸合酶（ALAS）催化血红素生物合成的第一个关键步骤。先前的研究表明存在红系和非红系 ALAS 同工酶。我们分离出了编码普遍表达的管家 ALAS 同工酶和一种相关但不同的红细胞特异性同工酶的 cDNA。利用这些不同的 cDNA，通过体细胞杂交和原位杂交技术，将人类 ALAS 管家基因 (ALAS1) 和人类红细胞特异性基因 (ALAS2) 分别定位到染色体 3p21 和 X。在分析的所有 26 个人成纤维细胞/鼠 (RAG) 体细胞杂交克隆中，ALAS1 基因与 3 号染色体一致，但在 26 个克隆中的至少 6 个克隆中，ALAS1 基因与所有其他染色体不一致。 ALAS1 到 3p21 的区域定位是通过使用 125I 标记的人 ALAS1 cDNA 进行原位杂交来完成的。在 3 号染色体上观察到的 43 个颗粒中，63% 位于 3p21 区域。通过检查与 ALAS2 cDNA 杂交的 30 个体细胞杂交系的 DNA 组来指定编码 ALAS2 的基因。在分析的所有 30 个杂交细胞系中，ALAS2 基因与人类 X 染色体分离，并且在 30 个杂交细胞系中至少有 8 个与所有其他染色体不一致。这些结果证实存在两个独立但相关的编码人类 ALAS 的基因。此外，ALAS2 基因在 X 染色体上的定位以及 X 连锁铁粒幼细胞贫血中观察到的 ALAS 活性降低表明，这种疾病可能是由于红细胞特异性基因的突变所致。
.delta.-Aminolevulinate synthase (ALAS) catalyzes the first committed step of heme biosynthesis. Previous studies suggested that there were erythroid and nonerythroid ALAS isozymes. We have isolated cDNAs encoding the ubiquitously expressed housekeeping ALAS isozyme and a related, but distinct, erythroid-specific isozyme. Using these different cDNAs, the human ALAS housekeeping gene (ALAS1) and the human erythroid-specific (ALAS2) gene have been localized to chromosomes 3p21 and X, respectively by somatic cell hybrid and in situ hybridization techniques. The ALAS1 gene was concordant with chromosome 3 in all 26 human fibroblast/murine(RAG) somatic cell hybrid clones analyzed and was discordant with all other chromosomes in at least 6 of 26 clones. The regional localization of ALAS1 to 3p21 was accomplished by in situ hybridization using the 125I-labeled human ALAS1 cDNA. Of the 43 grains observed over chromosome 3, 63% were localized to the region 3p21. The gene encoding ALAS2 was assigned by examination of a DNA panel of 30 somatic cell hybrid lines hybridized with the ALAS2 cDNA. The ALAS2 gene segregated with the human X chromosome in all 30 hybrid cell lines analyzed and was discordant with all other chromosomes in at least 8 of the 30 hybrids. These results confirm the the existence of two independent, but related, genes encoding human ALAS. Furthermore, the mapping of the ALAS2 gene to the X chromosome and the observed reduction in in ALAS activity in X-linked sideroblastic anemia suggest that this disorder may be due to a mutation in the erythroid-specific gene.