Abstract
A large, multigenerational family with dominantly inherited hypercholesterolemia was analyzed for genetic linkage between blood levels of low-density lipoprotein (LDL) cholesterol and the locus for the LDL receptor. A genetic marker was identified by restriction fragment length polymorphism (RFLP) in a cloned segment of the LDL receptor gene. We found no exceptions to segregation of the high-LDL cholesterol phenotype with a unique allele at the LDL receptor locus in this pedigree; tight linkage was indicated by a maximum lod score of 7.52 at theta = 0. Knowledge of the LDL receptor genotype will enable investigators to study variability of phenotypic expression in response to environmental influences or to different genetic determinants.
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- Barker D., Schafer M., White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell. 1984 Jan;36(1):131–138. doi: 10.1016/0092-8674(84)90081-3. [DOI] [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. Expression of the familial hypercholesterolemia gene in heterozygotes: mechanism for a dominant disorder in man. Science. 1974 Jul 5;185(4145):61–63. doi: 10.1126/science.185.4145.61. [DOI] [PubMed] [Google Scholar]
- Conneally P. M., Edwards J. H., Kidd K. K., Lalouel J. M., Morton N. E., Ott J., White R. Report of the Committee on Methods of Linkage Analysis and Reporting. Cytogenet Cell Genet. 1985;40(1-4):356–359. doi: 10.1159/000132186. [DOI] [PubMed] [Google Scholar]
- Elston R. C., Stewart J. A general model for the genetic analysis of pedigree data. Hum Hered. 1971;21(6):523–542. doi: 10.1159/000152448. [DOI] [PubMed] [Google Scholar]
- Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499–502. [PubMed] [Google Scholar]
- Goldstein J. L., Dana S. E., Brunschede G. Y., Brown M. S. Genetic heterogeneity in familial hypercholesterolemia: evidence for two different mutations affecting functions of low-density lipoprotein receptor. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1092–1096. doi: 10.1073/pnas.72.3.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hobbs H. H., Lehrman M. A., Yamamoto T., Russell D. W. Polymorphism and evolution of Alu sequences in the human low density lipoprotein receptor gene. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7651–7655. doi: 10.1073/pnas.82.22.7651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rautela G. S., Liedtke R. J. Automated enzymic measurement of total cholesterol in serum. Clin Chem. 1978 Jan;24(1):108–114. [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- White R., Leppert M., Bishop D. T., Barker D., Berkowitz J., Brown C., Callahan P., Holm T., Jerominski L. Construction of linkage maps with DNA markers for human chromosomes. Nature. 1985 Jan 10;313(5998):101–105. doi: 10.1038/313101a0. [DOI] [PubMed] [Google Scholar]
- Williams R. R., Hasstedt S. J., Wilson D. E., Ash K. O., Yanowitz F. F., Reiber G. E., Kuida H. Evidence that men with familial hypercholesterolemia can avoid early coronary death. An analysis of 77 gene carriers in four Utah pedigrees. JAMA. 1986 Jan 10;255(2):219–224. [PubMed] [Google Scholar]