Molecular Genetic Diagnosis of a Family with Hypercholesterolemia by a Mismatched PCR-RFLP Method for Genotyping Single Base Substitution of the LDL Receptor Gene
| Autor: | Emi Yamaki, Paul N. Hopkins, Roger R. Williams, Tsunenori Hirayama, Lily Wu, Mitsuru Emi |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Adolescent Genotype Base Pair Mismatch Coronary Disease Locus (genetics) Familial hypercholesterolemia Biology Polymerase Chain Reaction Hyperlipoproteinemia Type II chemistry.chemical_compound medicine Humans Genotyping Aged Genetics Cholesterol Cholesterol LDL Middle Aged medicine.disease Molecular biology Restriction enzyme Receptors LDL chemistry LDL receptor lipids (amino acids peptides and proteins) Restriction fragment length polymorphism Cardiology and Cardiovascular Medicine Polymorphism Restriction Fragment Length |
| Zdroj: | Japanese Heart Journal. 39:681-686 |
| ISSN: | 1348-673X 0021-4868 |
| DOI: | 10.1536/ihj.39.681 |
| Popis: | Plasma lipid and lipoprotein levels reflect in part the influence of relevant genetic loci. Defects at some of these loci account for specific types of dyslipoproteinemia occurring with regularity among family members. In the course of familial investigations of coronary artery disease, we identified an family in which several members were affected with elevated low density lipoprotein (LDL) cholesterol levels. To study the genetic defects responsible for plasma lipoprotein abnormality in this pedigree, we developed a simple method for genotyping a single base substitution that does not affect a restriction recognition enzyme site in exon 10 of the LDL receptor gene. Using our mismatched PCR method, this G- > A substitution at nucleotide 1413 could be genotyped in the form of a biallelic restriction fragment length polymorphism (RFLP) after digestion with restriction enzyme Hpa II. Linkage analysis using this molecular method demonstrated that the defect at the LDL receptor locus is responsible for elevated LDL cholesterol phenotype observed in this family by segregation of defective alleles at the LDL receptor locus with the disease (peak decimal logarithm of odds score > 3.0). |
| Databáze: | OpenAIRE |
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