The Impact of BRCA1 on Spina Bifida Meningomyelocele Lesions
| Autor: | Terri M. King, Kit Sing Au, Hope Northrup, Irene Townsend, Jack M. Fletcher, Timothy J. Kirkpatrick, Gayle H. Tyerman, Christina Davidson, Lawrence C. Shimmin |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Heterozygote Meningomyelocele endocrine system diseases Genes BRCA1 Gene Expression Single-nucleotide polymorphism Biology Lesion Genetics medicine Humans International HapMap Project Allele skin and connective tissue diseases Spinal Dysraphism Alleles Genetics (clinical) DNA Primers Base Sequence Spina bifida Homozygote Haplotype Infant Newborn Heterozygote advantage medicine.disease Phenotype Haplotypes Genetic marker Female medicine.symptom Microsatellite Repeats |
| Zdroj: | Annals of Human Genetics. 71:719-728 |
| ISSN: | 1469-1809 0003-4800 |
| DOI: | 10.1111/j.1469-1809.2007.00377.x |
| Popis: | Summary We examined the BRCA1 gene in 268 patients, and their parents, with a specific diagnosis of spina bifida meningomyelocele (SBMM). We genotyped two intragenic microsatellite markers (BRCA1 D17S1323, BRCA1 D17S1322) and 2 single nucleotide polymorphisms (A1186G, A4956G) in our patients. Transmission disequilibrium testing (TDT) showed significant association with A4956G, but not with A1186G. Extended TDT demonstrated over-transmission of the 17GT allele in BRCA1 D17S1323 and the 14GTT allele in BRCA1 D17S1322, and under-transmission of the 20GT allele in BRCA1 D17S1323 and the 16GTT allele in BRCA1 D17S1322. Our data included location of the rostral edge of the lesion. Individuals homozygous for the 17GT allele for BRCA1 D17S1323 were more likely to have SB lesions located caudally, while heterozygotes with the 17GT allele for BRCA1 D17S1323 had a more rostral lesion. Individuals heterozygous for the 16GTT allele of BRCA1 D17S1322 were more likely to have rostral lesions. We measured gene expression in CEPH members and demonstrated differential expression levels of BRCA1 associated with these polymorphisms. Integrating our data with HapMap findings showed that the polymorphic markers are associated with distinct haplotypes. We conclude that the BRCA1 gene is associated with SBMM and participates in the phenotypic variability seen in SBMM. |
| Databáze: | OpenAIRE |
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