RESUMO
PURPOSE: To investigate whether the human LMTK2 and PARP-2 gene defects are associated with azoospermia by meiotic arrest, mutational analysis was performed on Japanese men with azoospermia. METHODS: Via direct sequencing, mutational screening was carried out on the exon region of the genes, using genomic DNAs from 18 Japanese men. Statistical analysis was done on the detected single nucleotide polymorphisms (SNPs) in the patients and normal controls. RESULTS: Nine SNPs were detected in LMTK2 and five SNPs were detected in PARP-2. There were no significant differences in the genotype distribution and allele frequencies between the two groups in LMTK2. However, the genotype frequency of heterozygotes in SNP1 of PARP-2 was higher in the patient group. The haplotype analysis revealed that SNP1-SNP4 (T-A) of PARP-2 was significantly more frequent in the patient group. CONCLUSION: The PARP-2 gene might be associated with azoospermia by meiotic arrest in humans.
Assuntos
Azoospermia/genética , Meiose , Proteínas de Membrana/genética , Poli(ADP-Ribose) Polimerases/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Azoospermia/diagnóstico , Análise Mutacional de DNA , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Japão , MasculinoRESUMO
Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis were identified by microarray analysis of human testicular tissue. One of these is spermatogenesis-associated 17 (SPATA17). To investigate whether defects in the SPATA17 gene are associated with azoospermia due to meiotic arrest, a mutational analysis was conducted, in which the SPATA17 coding regions of 18 Japanese patients with this condition were sequenced. A statistical analysis was carried out that included 18 patients with meiotic arrest, 20 patients with Sertoli-cell-only syndrome (SCOS) and 96 healthy control men. No mutations were found in SPATA17. However, three coding single nucleotide polymorphisms (cSNPs: SNP1-SNP3) were detected in the patients with meiotic arrest. No significant differences in the genotype or allele frequencies of SNP1 and SNP2 were found between patients with meiotic arrest and the others. However, the frequency of the SNP3 allele was significantly elevated in the meiotic arrest group (P < 0.05). This study suggests that SPATA17 may play a critical role in human spermatogenesis, especially in meiosis.
Assuntos
Infertilidade Masculina/genética , Meiose/genética , Espermatogênese/genética , Povo Asiático/genética , Análise Mutacional de DNA , Humanos , Japão , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
PURPOSE: To investigate whether defects in human PRDM9, CDK2 and PSMC3IP are associated with azoospermia Mutational analysis was performed in Japanese patients with azoospermia caused by meiotic arrest. METHODS: Mutational screening of the coding regions of human PRDM9, CDK2 and PSMC3IP was done by direct sequencing using genomic DNA from 18 Japanese patients. Statistical analysis of the detected coding single nucleotide polymorphisms (cSNPs) in patients and normal control men was then carried out. RESULTS: One cSNP was detected in CDK2 and PSMC3IP. There were no significant differences in genotype distribution and allele frequencies between the patient and control groups in these two genes. However, three novel cSNPs were detected in the PRDM9. The genotype and allele frequencies of heterozygotes in SNP2 and SNP3 of PRDM9 were significantly higher in the patient group than in the control group. CONCLUSION: We found a possible association between PRDM9 and azoospermia by meiotic arrest.
Assuntos
Azoospermia/genética , Meiose/genética , Proteínas Metiltransferases/genética , Alelos , Azoospermia/enzimologia , Quinase 2 Dependente de Ciclina/genética , DNA/química , DNA/genética , Histona Metiltransferases , Histona-Lisina N-Metiltransferase , Humanos , Japão , Masculino , Proteínas Nucleares/genética , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Transativadores/genética , Fatores de Transcrição/genéticaRESUMO
The MBX gene is a novel paired-type homeobox gene. It plays a number of critical roles in the development of the eyes in the zebrafish. The knockdown of the mbx expression by morpholino antisense oligonucleotides leads to a reduction in the size of eyes and tectum in the zebrafish. We investigated whether the human MBX gene was associated with susceptibility to microphthalmia by analyzing four Korean families demonstrating microphthalmia with congenital cataract. Mutational analysis was performed on the human MBX gene using these families. However, no mutations could be detected. Therefore, no indications were found for an association between the MBX gene and microphthalmia with congenital cataract in humans.
Assuntos
Catarata/genética , Predisposição Genética para Doença , Microftalmia/genética , Mutação , Fatores de Transcrição Otx/genética , Análise Mutacional de DNA , Feminino , Humanos , Coreia (Geográfico) , Masculino , Fatores de Transcrição Otx/isolamento & purificação , LinhagemRESUMO
FK506-binding protein 6 (Fkbp6) is a member of a gene family containing a prolyl isomerase/FK506-binding domain and tetratricopeptide protein-protein interaction domains. Recently, the targeted inactivation of Fkbp6 in mice has been observed to result in aspermic males and the absence of normal pachytene spermatocytes. The loss of Fkbp6 results in abnormal pairing and a misalignment of the homologous chromosomes, and in non-homologous partner switches and autosynapsis of the X chromosome cores in meiotic spermatocytes. In this study, we analyzed whether human FKBP6 gene defects might be associated with human azoospermia. We performed a mutation analysis in all the coding regions of the human FKBP6 gene in 19 patients with azoospermia resulting from meiotic arrest. The expression of the human FKBP6 gene was specific to the testis, and a novel polymorphism site, 245C --> G (Y60X) could be found in exon 3. Our findings suggest that the human FKBP6 gene might be imprinted in the testis based on an analysis using two polymorphism sites.