Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia, an inherited inability to synthesize cortisol that occurs in 1 in 10,000-15,000 births. Affected females are born with ambiguous genitalia, a condition that can be ameliorated by administering dexamethasone to the mother for most of gestation. Prenatal diagnosis is required for accurate treatment of affected females as well as for genetic counseling purposes. Approximately 95% of mutations causing this disorder result from recombinations between the gene encoding the 21-hydroxylase enzyme (CYP21) and a linked, highly homologous pseudogene (CYP21P). Approximately 20% of these mutations are gene deletions, and the remainder are gene conversions that transfer any of nine deleterious mutations from the CYP21P pseudogene to CYP21. We describe a methodology for genetic diagnosis of 21-hydroxylase deficiency that utilizes gene-specific PCR amplification in conjunction with thermostable DNA ligase to discriminate single nucleotide variations in a multiplexed ligation detection assay. The assay has been designed to be used with either fluorescent or radioactive detection of ligation products by electrophoresis on denaturing acrylamide gels and is readily adaptable for use in other disease systems.
 ...
PMID:Detection of steroid 21-hydroxylase alleles using gene-specific PCR and a multiplexed ligation detection reaction. 853 65

Recently, by using a probe for the nuclear DNA repair enzyme poly(ADP-ribose) polymerase gene, a pseudogene was found on the long arm of chromosome 13. RFLP analysis demonstrates the presence of a common "A" allele and a rare "B" allele, which has a deletion of approximately 200 bp. This deletion occurs more frequently in blacks than in whites in the United States. In two B-cell malignancies, Burkitt's and follicular lymphomas, there is a marked increased frequency of the expression of the B allele. Thus, we have analyzed the frequency of this allele in another B-cell malignancy, multiple myeloma (MM), which is also more frequently observed in blacks. We studied 97 patients with MM (41 black and 56 white patients) and 30 patients with the related disorder monoclonal gammopathy of undetermined significance (MGUS; 13 black and 17 white patients). The results demonstrate that the overall frequency of B allele expression (37%) is higher than in a noncancer control population (23%; P < 0.01). This difference is mainly due to the much higher frequency of B expression in black patients (52 versus 35% in black controls; P < 0.01), whereas there is no significant difference in white patients (18 versus 14% in white controls). Overall, B allelic frequency is similar in patients with MM and MGUS. Matched germline and tumor DNA show identical patterns of expression of these alleles. These results suggest germline B allelic expression predisposes one to MM and MGUS.
 ...
PMID:Deletion of genetic material from a poly(ADP-ribose) polymerase-like gene on chromosome 13 occurs frequently in patients with monoclonal gammopathies. 867 93