Cloning of the human cholesterol 7 alpha-hydroxylase gene (CYP7) and localization to chromosome 8q11-q12.
Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is a microsomal cytochrome P450 that catalyzes the first step in bile acid synthesis. In this paper, we describe the cloning, characterization, and chromosomal mapping of the human 7 alpha-hydroxylase gene (CYP7). The gene spans 10 kb and contains six exons and five introns. The exon-intron boundaries are completely conserved between the human and rat genes. Sequencing of the 5' flanking region revealed consensus recognition sequences for a number of liver-specific transcription factors. The human CYP7 gene was mapped to chromosome 8q11-q12 using both mouse-human somatic cell hybrids and in situ chromosomal hybridization studies. A total of four single-stranded conformation-dependent DNA polymorphisms and an Alu sequence-related polymorphism were identified. Of the individuals analyzed, 80% were heterozygous for at least one of these five polymorphisms. The localization and characterization of the human 7 alpha-hydroxylase gene, as well as the identification of polymorphisms, provide the molecular tools necessary to investigate the role of this gene in disorders of cholesterol and bile acid metabolism.
Cohen
J C
JC
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Cali
J J
JJ
Jelinek
D F
DF
Mehrabian
M
M
Sparkes
R S
RS
Lusis
A J
AJ
Russell
D W
DW
Hobbs
H H
HH
D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D006822:Hybrid Cells; D007438:Introns / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017385:Sequence Homology
D002790:Cholesterol 7-alpha-Hydroxylase