title: Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest.
abstract: Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Mouse meiotic mutant mei1 (meiosis defective 1) was isolated by a screening of infertile mice. Male mei1 mice have azoospermia due to meiotic arrest, and the mouse Mei1 gene is responsible for the mei1 phenotype. To investigate whether human MEI1 gene defects are associated with azoospermia by meiotic arrest, we isolated the human MEI1 cDNA based on the mouse Mei1 amino acid sequence. MEI1 is expressed specifically in the testis. Mutational analysis by direct sequencing of all MEI1 coding regions was performed in 27 men (13 European Americans, 13 Israeli and 1 Japanese) having azoospermia due to complete early meiotic arrest. This identified four novel, coding single-nucleotide-polymorphisms (cSNPs), i.e., SNP1 (T909G), SNP2 (A1582G), SNP3 (C1791A) and SNP4 (C2397T) in exons 4, 8, 9 and 14, respectively. Using these cSNPs, an association study was carried out between 26 non-Japanese patients with azoospermia and two sets of normal control men (61 normal European Americans and 60 Israelis). Consequently, SNP3 and SNP4 were shown to be associated with azoospermia among European Americans (P =0.0289 and P =0.0299 for genotype and allele frequencies at both the polymorphic sites, respectively), although no such association was observed among Israelis (P >0.05). Haplotype estimation revealed that the frequencies of SNP3-SNP4 (C-T), SNP3-SNP4 (A-C) and SNP3-SNP4 (A-T) were higher in the European American patients, and the frequency of SNP3-SNP4 (A-T) was also higher than in both control groups. These results suggest that MEI1 may play a role in meiosis during spermatogenesis, especially in European Americans.
authors: Department of Obstetrics and Gynecology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa, 078-8510, Japan.
authors: Hisashi
authors: H
authors: Sato
authors: Department of Obstetrics and Gynecology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa, 078-8510, Japan. toshim@asahikawa-med.ac.jp.
authors: Toshinobu
authors: T
authors: Miyamoto
authors: Institute for the Study of Fertility, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Leah
authors: L
authors: Yogev
authors: Department of Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors: Mikio
authors: M
authors: Namiki
authors: Department of Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors: Eitesu
authors: E
authors: Koh
authors: Department of Obstetrics and Gynecology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa, 078-8510, Japan.
authors: Hiroaki
authors: H
authors: Hayashi
authors: Department of Obstetrics and Gynecology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa, 078-8510, Japan.
authors: Yoshihito
authors: Y
authors: Sasaki
authors: Department of Obstetrics and Gynecology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa, 078-8510, Japan.
authors: Mutsuo
authors: M
authors: Ishikawa
authors: Scott Department of Urology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors: Dolores J
authors: DJ
authors: Lamb
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Naomichi
authors: N
authors: Matsumoto
authors: Department of Molecular Developmental Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors: Ohad S
authors: OS
authors: Birk
authors: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|SORST, JST, Kawaguchi, Japan.
authors: Norio
authors: N
authors: Niikawa
authors: Department of Obstetrics and Gynecology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa, 078-8510, Japan.
authors: Kazuo
authors: K
authors: Sengoku