Testing for genetic associations with the PAX gene family in a spina bifida population
| Autor: | Hope Northrup, Susan H. Blanton, Kelly A. Volcik, M. C. Kruzel, R. J. Mier, I. T. Townsend, Gayle H. Tyerman |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Adolescent Genotype Population DNA Mutational Analysis Locus (genetics) Biology Genetic determinism Linkage Disequilibrium Gene Frequency Humans Paired Box Transcription Factors Genetic Testing Neural Tube Defects Allele education Child Dinucleotide Repeats Gene Spinal Dysraphism Genetics (clinical) Alleles Genetics Family Health education.field_of_study Polymorphism Genetic Pax genes Transmission disequilibrium test DNA DNA-Binding Proteins Genetic marker Child Preschool Multigene Family Female Transcription Factors |
| Zdroj: | American journal of medical genetics. 110(3) |
| ISSN: | 0148-7299 |
| Popis: | Neural tube defects (NTDs) are among the most common severely disabling birth defects in the United States, affecting approximately 1–2 of every 1,000 live births. The etiology of NTDs is multifactorial, involving the combined action of both genetic and environmental factors. A nonparametric linkage method, the transmission disequilibrium test (TDT), was utilized to determine if the genes in the PAX family play a role in the formation of NTDs. DNA from 459 spina bifida (SB) patients and their parents (430 mothers and 239 fathers, for a total population of 1,128 subjects) was tested for linkage and association utilizing polymorphic markers from within or very close to the PAX genes of interest. Significant findings were obtained for the following markers: marker locus D20S101 flanking the PAX1 gene (P = 0.019), marker locus D1S228 within the PAX7 gene (P = 0.011), and marker locus D2S110 within the PAX8 gene (P = 0.013). Even though our findings are only mildly significant, given the known expression patterns of the PAX genes in development and the availability of their sequences, we elected to follow up these results by testing these genes directly for mutations utilizing single-strand conformational analysis (SSCA) and direct sequencing. Multiple variations were detected in each of the PAX genes with significant TDT results; however, these variations were not passed from parent to child in phase with the positively transmitted allele. Therefore, it is unlikely that these variations contribute to susceptibility for SB, but rather are previously unreported polymorphisms. © 2002 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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