Gene structure, polymorphism and mapping of the human endothelial nitric oxide synthase gene.
Endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) is synthesized from L-Arginine by the endothelial, constitutive, NO synthase. No facilitate genetic studies, we have cloned the human endothelial NO synthase gene and determined its structure. The gene is composed of 26 exons, ranging from 68 to 579 bp and spans 22 kb. We determined the transcription start point using human lung mRNA. No TATA-box was found at the expected distance from the transcription start point and several consensus sequences for transcription factors, including a shear-stress responsive element were identified in the 5'-flanking region. A highly polymorphic (CA) repeat within intron 13 was studied, allowing the precise genetic mapping of the gene to chromosome 7, within a 4 cM interval delimited by genethon markers AFM199Zd4 and AFM074Xg5.
Nadaud
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S
INSERM U36, Collège de France, Paris.
Bonnardeaux
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A
Lathrop
M
M
Soubrier
F
F
D000483:Alleles; D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D003360:Cosmids; D017931:DNA Primers; D004276:DNA, Satellite / Q000235:genetics; D004727:Endothelium / Q000201:enzymology*; D005091:Exons; D005260:Female; D015698:Genomic Library; D006801:Humans; D007438:Introns; D008168:Lung / Q000201:enzymology; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase; D010920:Placenta / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D017931:DNA Primers; D004276:DNA, Satellite; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases