HASPIN is a serine/threonine protein kinase predominantly expressed during spermatogenesis and localized in the nucleus. The HASPIN gene is conserved from yeast to mammals and plants. To investigate any possible assoc...HASPIN is a serine/threonine protein kinase predominantly expressed during spermatogenesis and localized in the nucleus. The HASPIN gene is conserved from yeast to mammals and plants. To investigate any possible associations between HASPIN polymorphisms and impaired spermatogenesis in Japanese males, we screened for mutations in the HASPIN coding sequence (CDS) using DNA from 282 sterile male patients and 262 fertile male volunteers. Polymorphisms were found at 10 positions within the HASPIN CDS. Among these 10 polymorphisms, 5 were found only in the infertile group, 3 of which were nonsynonymous. These polymorphisms found only in the infertile patients may be a cause of male infertility and thus valuable candidates for further study of this condition.展开更多
Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for ch...Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.展开更多
文摘HASPIN is a serine/threonine protein kinase predominantly expressed during spermatogenesis and localized in the nucleus. The HASPIN gene is conserved from yeast to mammals and plants. To investigate any possible associations between HASPIN polymorphisms and impaired spermatogenesis in Japanese males, we screened for mutations in the HASPIN coding sequence (CDS) using DNA from 282 sterile male patients and 262 fertile male volunteers. Polymorphisms were found at 10 positions within the HASPIN CDS. Among these 10 polymorphisms, 5 were found only in the infertile group, 3 of which were nonsynonymous. These polymorphisms found only in the infertile patients may be a cause of male infertility and thus valuable candidates for further study of this condition.
文摘Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.
