MOLECULAR-CLONING AND CHARACTERIZATION OF THE HUMAN BETA-LIKE GLOBIN GENE-CLUSTER
MOLECULAR-CLONING AND CHARACTERIZATION OF THE HUMAN BETA-LIKE GLOBIN GENE-CLUSTER
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DOI:
10.1016/0092-8674(80)90087-2
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发表时间:
1980-01-01
期刊:
影响因子:
64.5
通讯作者:
MANIATIS, T
中科院分区:
文献类型:
--
作者:
FRITSCH, EF;LAWN, RM;MANIATIS, T
The genes encoding human embryonic (.epsilon.), fetal (G.gamma., A.gamma.) and adult (.delta., .beta.) .beta.-like globin polypeptides were isolated as a set of overlapping cloned DNA fragments from bacteriophage .lambda. libraries of high MW (15-20 kb) [kilobases] chromosomal DNA. The 65 kb of DNA represented in these overlapping clones contains the genes for all 5 .beta.-like polypeptides, including the embryonic .epsilon.-globin gene, for which the chromosomal location was previously unknown. All 5 genes are transcribed from the same DNA strand and are arranged in the order 5''-.epsilon.-(13.3 kb)-G.gamma.-(3.5 kb)-A.gamma.-(13.9 kb)-.delta.-(5.4 kb)-.beta.-3''. Thus, the genes are positioned on the chromosome in the order of their expression during development. In addition to the 5 known .beta.-like globin genes, 2 other .beta.-like globin sequences were detected which do not correspond to known polypeptides. One of these sequences was mapped to the A.gamma.-.delta. intergenic region while the other is located 6-9 kb 5'' to the .epsilon. gene. Cross hybridization experiments between the intergenic sequences of the gene cluster revealed a nonglobin repeat sequence (*) which is interspersed with the globin genes in the following manner: 5''-**.epsilon.-*G.gamma.-A.gamma.*-**.delta.-.beta.*-3''. Fine structure mapping of the region located 5'' to the .delta.-globin gene revealed 2 repeats with a maximum size of 400 bp [base pairs] which are separated by .apprx. 700 bp of DNA not repeated within the cluster. Preliminary experiments indicate that this repeat family is also repeated many times in the human genome.