title: The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene.
abstract: Niemann-Pick C (NP-C) is a fatal autosomal recessive storage disorder characterized by progressive neurodegeneration and variable hepatosplenomegaly. At the cellular level, cells derived from an affected individual accumulate unesterified cholesterol in lysosomes when cultured with low-density lipoprotein. The NP-C gene was identified at 18q11. The transcript is 4.9 kb encoding a 1278-amino-acid protein. We have defined the genomic structure of NPC1 along with the 5' flanking sequence. The NPC1 gene spans greater than 47 kb and contains 25 exons. Exons range in size from 74 to 788 bp with introns ranging in size from 0.097 to 7 kb. All intron/exon boundaries follow the GT/AG rule. The 5' flanking sequence has a CpG island containing multiple Sp1 sites indicative of a promoter region. The CpG island is located in the 5' flanking sequence, exon 1 and the 5' end of intron 1. We have also identified multiple single nucleotide polymorphisms in the coding and intronic sequences.
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, Maryland, 20892, USA. jill_morris@merck.com
authors.forename: J A
authors.initials: JA
authors.lastname: Morris
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: K G
authors.initials: KG
authors.lastname: Coleman
authors.forename: J
authors.initials: J
authors.lastname: Nagle
authors.forename: P G
authors.initials: PG
authors.lastname: Pentchev
authors.forename: E D
authors.initials: ED
authors.lastname: Carstea
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D015894:Genome, Human; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011506:Proteins