Genetic Linkage Studies of Thyroid Peroxidase (TPO) Gene in Families with TPO Deficiency*
| Autor: | Meyer Knobel, B L Wajchenberg, Ampica Mangklabruks, Ana-Elisa Correa Billerbeck, Geraldo Medeiros-Neto, Leslie J. DeGroot, Nancy J. Cox |
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| Rok vydání: | 1991 |
| Předmět: |
Male
endocrine system medicine.medical_specialty TaqI Genetic Linkage Endocrinology Diabetes and Metabolism Clinical Biochemistry Thyroid Gland Thyrotropin Biology Iodide Peroxidase Biochemistry chemistry.chemical_compound Endocrinology Bacterial Proteins Genetic linkage Thyroid peroxidase Internal medicine Complementary DNA medicine Humans Deoxyribonucleases Type II Site-Specific Thyrotropin-Releasing Hormone Gene BglII Genetics Biochemistry (medical) DNA DNA Restriction Enzymes Iodides Pedigree Thyroxine Restriction enzyme chemistry biology.protein Triiodothyronine Female Lod Score Restriction fragment length polymorphism Polymorphism Restriction Fragment Length |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 72:471-476 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem-72-2-471 |
| Popis: | We have conducted biochemical and genetic studies in five unrelated families (denoted A, C, R, P, and G), which included nine goitrous subjects (five borderline euthyroid and four hypothyroid) with complete (n = 6) or partial (n = 3) thyroid peroxidase (TPO) deficiency. Thyroid tissue was obtained from four subjects, respectively, in families A, C, and R. No iodide organification or iodide incorporation into protein was present in families A and C. The two affected siblings in family R had a low normal tissue thyroperoxidase activity. Using a 0.8-kilobase (kb) cDNA clone (pM5) encoding 30% of the cDNA of human TPO gene down-stream from basepair 730 and four restriction enzymes (TaqI, PstI, BglI, and BglII), we were unable to find any polymorphisms in family A. In another family (C) blood samples were obtained from only two family members, and consequently, it was not possible to determine linkage. DNA from families G, P, and C showed biallelic polymorphisms when digested with BglII, at 8.7 and 8.5 kb. In family R we detected two biallelic polymorphisms at 9.0 and 8.5 kb, and the 9.0-kb bands were clearly larger than 8.7-kb bands found in the other subjects. Also, there was an absence of a 4.0- to 3.9-kb band that may represent a partial gene deletion. With PstI-restricted DNA a possible deletion of 5.5-kb band was also present in affected siblings of family R. The logarithm of odds (Lod) score analyzed from the family with inbreeding (R) was compatible with linkage of disease and the TPO gene (Lod = 2.08). When this method was used with families G and P, the Lod score was inconsistent with linkage between disease and the TPO gene. These data suggest that the cause of TPO deficiency in these families is heterogeneous. However, the restriction fragment length polymorphism pattern of BglII-restricted DNA in the R family strongly suggests that a partial TPO gene deletion has occurred in this family. |
| Databáze: | OpenAIRE |
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