Assignment of the human gene for the low density lipoprotein receptor to chromosome 19: Synteny of a receptor, a ligand, and a genetic disease

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The availability of a species-specific- monoclonal antibody that recognizes the low density lipoprotein (LDL) receptor of human but not hamster origin permitted assignment of the structural gene for the human receptor to chromosome 19. The antibody was used to detect the human LDL receptor in a series of hamster-human somatic cell hybrids by two assays: (i) a structural assay that measured cellular incorporation of [35S]methionine into immunoprecipitable receptor and (ii) a functional assay that measured the rate of receptor-dependent uptake and degradation of the 125I-labeled anti-receptor monoclonal antibody. Both assays showed that the human LDL receptor was expresed in 15 out of 20 hybrid cell lines. Expression of the human LDL receptor was 100% concordant with the presence of human chromosome 19; all other human chromosomes showed at least 25% discordance. As expected, the gene for the LDL receptor (LDLR) is located on the same chromosome as the gene for the disease familial hypercholesterolemia, which has been previously mapped to chromosome 19 by pedigree studies and is caused by allelic mutations at the LDL receptor locus. The gene for apolipoprotein E, a ligand for the LDL receptor, is also known to be located on chromosome 19, raising the possibility of an evolutionary link between a protein ligand and its receptor.

Original languageEnglish (US)
Pages (from-to)2826-2830
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume81
Issue number9 I
StatePublished - 1984

Fingerprint

Synteny
Chromosomes, Human, Pair 19
Inborn Genetic Diseases
LDL Receptors
Ligands
Hybrid Cells
Human Chromosomes
Cricetinae
Genes
Monoclonal Antibodies
Hyperlipoproteinemia Type II
Apolipoproteins E
Pedigree
Methionine
Chromosomes
Cell Line
Mutation
human LDLR protein
Antibodies
Proteins

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

@article{7f1281414794488ca9ebabc3c59b3f2e,
title = "Assignment of the human gene for the low density lipoprotein receptor to chromosome 19: Synteny of a receptor, a ligand, and a genetic disease",
abstract = "The availability of a species-specific- monoclonal antibody that recognizes the low density lipoprotein (LDL) receptor of human but not hamster origin permitted assignment of the structural gene for the human receptor to chromosome 19. The antibody was used to detect the human LDL receptor in a series of hamster-human somatic cell hybrids by two assays: (i) a structural assay that measured cellular incorporation of [35S]methionine into immunoprecipitable receptor and (ii) a functional assay that measured the rate of receptor-dependent uptake and degradation of the 125I-labeled anti-receptor monoclonal antibody. Both assays showed that the human LDL receptor was expresed in 15 out of 20 hybrid cell lines. Expression of the human LDL receptor was 100{\%} concordant with the presence of human chromosome 19; all other human chromosomes showed at least 25{\%} discordance. As expected, the gene for the LDL receptor (LDLR) is located on the same chromosome as the gene for the disease familial hypercholesterolemia, which has been previously mapped to chromosome 19 by pedigree studies and is caused by allelic mutations at the LDL receptor locus. The gene for apolipoprotein E, a ligand for the LDL receptor, is also known to be located on chromosome 19, raising the possibility of an evolutionary link between a protein ligand and its receptor.",
author = "U. Francke and Brown, {M. S.} and Goldstein, {J. L.}",
year = "1984",
language = "English (US)",
volume = "81",
pages = "2826--2830",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "9 I",

}

TY - JOUR

T1 - Assignment of the human gene for the low density lipoprotein receptor to chromosome 19

T2 - Synteny of a receptor, a ligand, and a genetic disease

AU - Francke, U.

AU - Brown, M. S.

AU - Goldstein, J. L.

PY - 1984

Y1 - 1984

N2 - The availability of a species-specific- monoclonal antibody that recognizes the low density lipoprotein (LDL) receptor of human but not hamster origin permitted assignment of the structural gene for the human receptor to chromosome 19. The antibody was used to detect the human LDL receptor in a series of hamster-human somatic cell hybrids by two assays: (i) a structural assay that measured cellular incorporation of [35S]methionine into immunoprecipitable receptor and (ii) a functional assay that measured the rate of receptor-dependent uptake and degradation of the 125I-labeled anti-receptor monoclonal antibody. Both assays showed that the human LDL receptor was expresed in 15 out of 20 hybrid cell lines. Expression of the human LDL receptor was 100% concordant with the presence of human chromosome 19; all other human chromosomes showed at least 25% discordance. As expected, the gene for the LDL receptor (LDLR) is located on the same chromosome as the gene for the disease familial hypercholesterolemia, which has been previously mapped to chromosome 19 by pedigree studies and is caused by allelic mutations at the LDL receptor locus. The gene for apolipoprotein E, a ligand for the LDL receptor, is also known to be located on chromosome 19, raising the possibility of an evolutionary link between a protein ligand and its receptor.

AB - The availability of a species-specific- monoclonal antibody that recognizes the low density lipoprotein (LDL) receptor of human but not hamster origin permitted assignment of the structural gene for the human receptor to chromosome 19. The antibody was used to detect the human LDL receptor in a series of hamster-human somatic cell hybrids by two assays: (i) a structural assay that measured cellular incorporation of [35S]methionine into immunoprecipitable receptor and (ii) a functional assay that measured the rate of receptor-dependent uptake and degradation of the 125I-labeled anti-receptor monoclonal antibody. Both assays showed that the human LDL receptor was expresed in 15 out of 20 hybrid cell lines. Expression of the human LDL receptor was 100% concordant with the presence of human chromosome 19; all other human chromosomes showed at least 25% discordance. As expected, the gene for the LDL receptor (LDLR) is located on the same chromosome as the gene for the disease familial hypercholesterolemia, which has been previously mapped to chromosome 19 by pedigree studies and is caused by allelic mutations at the LDL receptor locus. The gene for apolipoprotein E, a ligand for the LDL receptor, is also known to be located on chromosome 19, raising the possibility of an evolutionary link between a protein ligand and its receptor.

UR - http://www.scopus.com/inward/record.url?scp=0013305055&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0013305055&partnerID=8YFLogxK

M3 - Article

C2 - 6326146

AN - SCOPUS:0013305055

VL - 81

SP - 2826

EP - 2830

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 9 I

ER -