Six DNA polymorphisms in the low density lipoprotein receptor gene: their genetic relationship and an example of their use for identifying affected relatives of patients with familial hypercholesterolaemia
| Autor: | J C Fruchart, Steve E. Humphries, Mary Seed, Sophie Delattre, Vilmundur Gudnason, V Clavey, L King-Underwood |
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| Jazyk: | angličtina |
| Rok vydání: | 1993 |
| Předmět: |
Proband
Male Linkage disequilibrium TaqI Cosegregation DNA Mutational Analysis Molecular Sequence Data Biology Polymerase Chain Reaction Linkage Disequilibrium Hyperlipoproteinemia Type II chemistry.chemical_compound Gene Frequency Genetics Humans Allele Allele frequency Genetics (clinical) Alleles Base Sequence DNA Molecular biology Pedigree chemistry Receptors LDL LDL receptor Female Restriction fragment length polymorphism Polymorphism Restriction Fragment Length Research Article |
| Popis: | We have determined the relative allele frequency and estimated linkage disequilibrium between six DNA polymorphisms of the low density lipoprotein (LDL) receptor gene. Polymorphisms were detected using the enzymes SfaNI, TaqI, StuI, HincII, AvaII, and NcoI after DNA amplification by the polymerase chain reaction. Strong linkage disequilibrium was detected between many of the pair wise comparisons in a sample of 60 patients heterozygous for familial hypercholesterolaemia (FH). Using the enzymes HincII, NcoI, and SfaNI, 85% of patients were heterozygous for at least one polymorphism and thus potentially informative for cosegregation studies. The polymorphisms were used to follow the inheritance of the defective allele of the LDL receptor gene in the relatives of a patient with FH. Assays of LDL receptor activity on lymphoblastoid cell lines from two members of the family was used to confirm that the proband, but not the hypercholesterolaemic brother, had a defect in the LDL receptor. In the family, none of the children had inherited the allele of the LDL receptor gene inferred to be defective. The problems associated with this cosegregation approach to identify relatives of patients with a clinical diagnosis of FH are discussed. |
| Databáze: | OpenAIRE |
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