Molecular Diagnostics of Genetic Diseases: Experience from Studies of DMD, APC, TSC1, and OPG Genes. Part 2
| Autor: | Ryszard Słomski, Robert Kalak, Jolanta Jura, Wanda Horst-Sikorska, David J. Kwiatkowski |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Genetics
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Nutrition and Dietetics Clinical Biochemistry Medicine (miscellaneous) Autosomal dominant trait Single-strand conformation polymorphism Biology Penetrance Molecular biology Exon medicine.anatomical_structure Molecular genetics medicine TSC1 Allele Gene |
| Zdroj: | Journal of Clinical Biochemistry and Nutrition. 28:129-141 |
| ISSN: | 1880-5086 0912-0009 |
| DOI: | 10.3164/jcbn.28.129 |
| Popis: | Tuberous sclerosis (TSC) is an autosomal dominant disease with variable penetrance, characterized by alterations in various organs including brain, heart, and kidneys. In about 2/3 of patients a family history of TSC is not observed. TSC is caused by a mutation in one of two genes-TSC1 or TSC2. Discovered recently, the TSC1 gene is composed of 23 exons; the first two exons are not expressed and exon 2 is alternatively spliced. Analysis of mutations was performed for patients, and mutations were identified, and found to be distributed in different exons. Approximately 75% the mutations could be detected by PCR-single-strand conformation polymorphism (SSCP) and PCR-heteroduplex (HD). All mutations identified in the group of patients led to premature termination of translation. Experiments performed over the last few years allowed the identification of three novel genes located in the 9q34 region (TSC1, RalGDS, and XPMC2H) and the characterization of structure, level of expression, and site of expression of the TSC1 gene. Osteoporosis is a common human disease and is under genetic control, with several genes most likely contributing to the development of the disorder. One of many gene candidates that could potentially regulate bone development is the osteoprotegerin (OPG) gene. Using PCR-SSCP and PCR-HD techniques, we investigated sequence variations in the human OPG gene in DNA samples from patients with osteoporosis and osteopenia and healthy controls. From seven detected polymorphisms five were intronic substitutions, IVS1+15C→T, IVS2+4C→T, IVS3-5C→T, IVS4-24C→A, IVS4+8A→C; one represented a two base pair deletion, IVS3+46delTC; and the last polymorphism, 9G→C, detected in exon 1 of the OPG gene, was associated with osteoporosis. The relative risk for osteoporosis is estimated to be 2.99 in individuals who carry allele C (95% confidence interval 1.06-8.41). |
| Databáze: | OpenAIRE |
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