Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical and genetic characterizations of two variants that occur in BRCA1 intron 8 are presented. The variant IVS8+2T-->C induces an aberrant transcript that deletes exon 8. This exon-skipping deletion disrupts the open reading frame by juxtaposing exon 7 and exon 9 in the aberrant splice product. Theoretically, 50 abnormal residues from reading frame 2 are translated following exon 7 before a stop codon is encountered. The chromosomal contribution to the relevant RNA species was tracked using a silent polymorphism at codon 694 (serine AGC or AGT). Nucleotide sequencing of this polymorphic codon demonstrated that the aberrant transcript was derived solely from the chromosome encoding AGT. The normally spliced productive transcript also displayed loss of heterozygosity and was derived solely from the chromosome encoding AGC at codon 694. Also, a haplotype analysis using a breast cancer patient database showed that the chromosome bearing serine 694-AGT carried IVS8+2T-->C. A second more common variant, IVS8-58delT, was characterized as a polymorphism. Analysis of RNA from patient samples used the same silent polymorphism at codon 694 and showed that the normal message was derived from both chromosomes.
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PMID:A characterization of genetic variants in BRCA1 intron 8 identifies a mutation and a polymorphism. 1047 26

Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.
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PMID:The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients. 2968 86