The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene

Niemann-Pick C (NP-C) is a fatal autosomal recessive storage disorder chara cterized 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 lipop rotein. The NP-C gene was identified at 18q11. The transcript is 4.9 kb enc oding a 1278-amino-acid protein. We have defined the genomic structure of N PC1 along with the 5' flanking sequence. The NPC1 gene spans greater than 4 7 kb and contains 25 exons. Exons range in size from 74 to 788 bp with intr ons ranging in size from 0.097 to 7 kb. All intron/exon boundaries follow t he GT/AG rule. The 5' flanking sequence has a CpG island containing multipl e Spl 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 i dentified multiple single nucleotide polymorphisms in the coding and intron ic sequences. (C) 1999 Academic Press.