Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR2 gene in heritable pulmonary arterial hypertension
| Autor: | Hideaki Yoshino, Toru Satoh, Shinobu Gamou, Yuki Aimi, Masae Ono, Akira Oka, Ryoji Yanagisawa, Keiichi Fukuda, Masaharu Kataoka |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Adolescent DNA Copy Number Variations Hypertension Pulmonary DNA Mutational Analysis Alu element Biology Gene mutation medicine.disease_cause Bone Morphogenetic Protein Receptors Type II Exon Chromosome Breakpoints Young Adult Japan Alu Elements Homologous chromosome medicine Humans Point Mutation Familial Primary Pulmonary Hypertension Child Homologous Recombination Genetics (clinical) Sequence Deletion Genetics Recombination Genetic Mutation BMPR2 Gene Exons Middle Aged medicine.disease Molecular biology Pulmonary hypertension Introns Pedigree Female Homologous recombination Genome-Wide Association Study |
| Zdroj: | Genetics in medicine : official journal of the American College of Medical Genetics. 15(12) |
| ISSN: | 1530-0366 |
| Popis: | The purpose of this study was to undertake thorough genetic analysis of the bone morphogenetic protein type 2 receptor (BMPR2) gene in patients with pulmonary arterial hypertension.We conducted a systematic analysis for larger gene rearrangements together with conventional mutation analysis in 152 pulmonary arterial hypertension patients including 43 patients diagnosed as having idiopathic pulmonary arterial hypertension and 10 diagnosed as having familial pulmonary arterial hypertension.Analysis of the BMPR2 gene revealed each of the four kinds of nonsense and frameshift mutations, one missense mutation, one splice-site mutation, and two types of exonic deletion. For cases in which exons 1-3 were deleted, the 5' and 3' break points were located in the AluY repeat sequences in the 5' side of the adjacent NOP58 gene and in the AluY repeat sequences in intron 3, suggesting an AluY-mediated nonallelic homologous recombination as the mechanism responsible for the deletion. For the case in which exon 10 was deleted, nonhomologous recombination took place between the AluSx site in intron 9 and a unique sequence in intron 10.Exonic deletions of BMPR2 account for at least part of BMPR2 mutations associated with heritable pulmonary arterial hypertension in Japan, as previously reported in other populations. One of our cases was mediated via Alu-mediated nonallelic homologous recombination and another was mediated via nonhomologous recombination. |
| Databáze: | OpenAIRE |
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