Localizing the human Niemann-Pick C gene to 18q11-12

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133994

Carstea, E D; Parker, C C; Fandino, L B ^[1]

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1. National Institutes of Health, Bethesda, MD (United States); and others

Niemann-Pick C (NPC) is an autosomal recessive neurovisceral lipid storage disorder characterized by abnormal processing and defective intracellular movement of endocytosed cholesterol. Multipoint genetic linkage analysis on 18 NPC families places the NPC locus within a 5 cM interval between loci D18S44 and D18S66, supported by the lod score Z{sub max}=123.61. Pairwise linkage analysis with marker D18S480 resulted in no obligate recombinations between it and the NPC gene in any of the sibling pairs. The resulting two point lod score was Z{sub max}=10.628 at {theta}=0.001. According to the physical map, both D18S44 and D18S480 are located on band 18q11 whereas D18S66 maps to 18q12, and therefore places NPC on the proximal long arm of chromosome 18. A single pedigree, family 19, demonstrated recombinations with markers that both define and flank the proposed NPC interval. In family 19, it was apparent that there was no correlation between the NPC-like phenotype and inheritance of the chromosome 18 region defined by D18S44 and D18S66. Based on heterogeneity testing, family 19 was excluded from linkage analysis. Therefore, in addition to mapping the NPC gene to proximal 18q, the NPC phenotype of family 19 suggests the existence of a separate gene that codes for an additional component required for intracellular movement of cholesterol.

• OSTI ID: 133994
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CHOLESTEROL
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 18
LIPIDS
METABOLIC DISEASES
METABOLISM
PATIENTS
PHENOTYPE
RECESSIVE MUTATIONS
STATISTICS
STORAGE