Nature Genetics
22, 336 - 345 (1999)
doi:10.1038/11905
Mutations in ABC1 in Tangier disease and familial high-density
lipoprotein deficiencyAngela Brooks-Wilson1, 10, Michel Marcil1, 10, Susanne M. Clee2, Lin-Hua Zhang1, Kirsten Roomp1, Marjel van Dam3, Lu Yu4, Carl Brewer5, Jennifer A. Collins1, Henri O.F. Molhuizen3, Odell Loubser2, B.F. Francis Ouelette2, Keith Fichter2, Katherine J.D. Ashbourne-Excoffon2, Christoph W. Sensen6, Stephen Scherer7, Stephanie Mott4, Maxime Denis4, Duane Martindale8, Jiri Frohlich9, Kenneth Morgan5, Ben Koop8, Simon Pimstone2, John J.P. Kastelein3, Jacques Genest Jr4
& Michael R. Hayden21
Xenon Bioresearch Inc., NRC Innovation Centre,
3250 East Mall, Vancouver, British Columbia,
V6T 1W5, Canada. 2
Centre for Molecular Medicine and Therapeutics, Children's
and Women's Hospital, University of British Columbia, 950 West
28 th Avenue, Vancouver, British Columbia
, V5Z 4H4, Canada. 3
Department of Vascular Medicine, G-I,
Room 146, Academic Medical Centre, Meibergdreef 9, 1105 AZ,
Amsterdam, The Netherlands.
4
Cardiovascular Genetics Laboratory, Clinical Research
Institute of Montreal, Montreal, Quebec, H2W
1R7, Canada. 5
Departments of Human Genetics and Medicine, Montreal
General Hospital, Room L10-109, McGill University, 1650 Cedar
Avenue, Montreal, Quebec, H3G 1A4,
Canada. 6
Institute for Marine Biosciences, NRC,
1411 Oxford Street, Halifax, Nova Scotia,
B3H 3Z1, Canada. 7
Hospital for Sick Children, University of Toronto,
Ontario, M5G 1X8, Canada. 8
Department of Biology, Centre for Environmental Health,
University of Victoria, British Columbia, V8W 3N5,
Canada. 9
Department of Pathology and Laboratory Medicine, University
of British Columbia, Vancouver, British Columbia,
V6T 1Z1, Canada. 10
These authors contributed equally to this work.
Correspondence should be addressed to Michael R. Hayden mrh@cmmt.ubc.caGenes have a major role in the control of high-density lipoprotein (HDL)
cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD)
families, confirmed 9q31 linkage and refined the disease locus to a limited
genomic region containing the gene encoding the ATP-binding cassette transporter
(ABC1). Familial HDL deficiency (FHA) is a more frequent cause of low
HDL levels. On the basis of independent linkage and meiotic recombinants,
we localized the FHA locus to the same genomic region as the TD locus. Mutations
in ABC1 were detected in both TD and FHA, indicating that TD and FHA
are allelic. This indicates that the protein encoded by ABC1 is a key
gatekeeper influencing intracellular cholesterol transport, hence we have
named it cholesterol efflux regulatory protein (CERP).
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