title: Association of a single-nucleotide polymorphism of the deleted-in-azoospermia-like gene with susceptibility to spermatogenic failure.
abstract: Single-strand conformation polymorphism analysis of exon-containing genomic DNA segments of the deleted-in-azoospermia-like (DAZL) gene was performed in 160 infertile Taiwanese men presenting with severe oligozoospermia and nonobstructive azoospermia. An A-->G transition at nucleotide 386 in exon 3 was identified. The mutation is located within the RNA-recognition motif (aa 32-117) domain of the DAZL protein and will lead to Thr54-->Ala change (T54A) of DAZL protein. Analysis of cDNA from testicular tissue of infertile carriers showed absence of expression for the T54A allele, implying that the allele carrying T54A polymorphism is hardly, if ever, expressed. The frequencies of T54A allele in patients and the control group were 7.39% and 0.86%, respectively (P = 0.0003). The phenotypes varied significantly in cases with heterozygous T54A polymorphism, ranging from hypospermatogenesis and maturation arrest to Sertoli cell-only syndrome. A combination of DAZ gene deletion and T54A polymorphism did not worsen the phenotype. Our findings provide strong evidence for the role of the autosomal DAZL gene in human spermatogenesis.
authors.affiliation: Department of Early Childhood Education and Nursery, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan.
authors.forename: Yen-Ni
authors.initials: YN
authors.lastname: Teng
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Lin
authors.forename: Ying-Hung
authors.initials: YH
authors.lastname: Lin
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Tsao
authors.forename: Chao-Chin
authors.initials: CC
authors.lastname: Hsu
authors.forename: Shio-Jean
authors.initials: SJ
authors.lastname: Lin
authors.forename: Wan-Ching
authors.initials: WC
authors.lastname: Tsai
authors.forename: Pao-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D000075364:Deleted in Azoospermia 1 Protein; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013091:Spermatogenesis / Q000235:genetics*; D013624:Taiwan; D014998:Y Chromosome
chemical_list: C095668:DAZ1 protein, human; C101358:DAZL protein, human; D000075364:Deleted in Azoospermia 1 Protein; D011506:Proteins; D016601:RNA-Binding Proteins