TY - JOUR
T1 - Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency
AU - Brooks-Wilson, Angela
AU - Marcil, Michel
AU - Clee, Susanne M.
AU - Zhang, Lin Hua
AU - Roomp, Kirsten
AU - Van Dam, Marjel
AU - Yu, Lu
AU - Brewer, Carl
AU - Collins, Jennifer A.
AU - Molhuizen, Henri O.F.
AU - Loubser, Odell
AU - Ouelette, B. F.Francis
AU - Fichter, Keith
AU - Ashbourne-Excoffon, Katherine J.D.
AU - Sensen, Christoph W.
AU - Scherer, Stephen
AU - Mott, Stephanie
AU - Denis, Maxime
AU - Martindale, Duane
AU - Frohlich, Jiri
AU - Morgan, Kenneth
AU - Koop, Ben
AU - Pimstone, Simon
AU - Kastelein, John J.P.
AU - Genest, Jacques
AU - Hayden, Michael R.
N1 - Funding Information:
We thank C. Du Souich for ascertaining family members with FHA; L. Levesques for help in designing the antisense experiments; B. Boucher for technical support; and C. Visser for administrative assistance, and the members of our laboratories, especially M. Fujiwara, for their useful comments. This is NRC publication No. 42299. This work was supported in part by grants from MRC Canada to M.R.H. and J.G. Jr; an operating grant from the Heart and Stroke Foundation of Canada to J.G. Jr and M.R.H.; and a grant from the Canadian Networks of Centres of Excellence (NCE-Genetics) to M.R.H. The research of K.M., B.K. and B.F.F.O. is also supported in part by NCE Genetics. H.O.F.M. was supported by a grant from the Dutch Heart Foundation. M.R.H. is an established investigator of the B.C. Children’s Hospital and MRC-PMAC Senior Scientist.
PY - 1999/8
Y1 - 1999/8
N2 - Genes 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).
AB - Genes 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).
UR - http://www.scopus.com/inward/record.url?scp=0032813808&partnerID=8YFLogxK
U2 - 10.1038/11905
DO - 10.1038/11905
M3 - Article
C2 - 10431236
AN - SCOPUS:0032813808
SN - 1061-4036
VL - 22
SP - 336
EP - 345
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -