The human Y chromosome's azoospermia factor b (AZFb) region: sequence, structure, and deletion analysis in infertile men.
Microdeletions of the Y chromosome long arm are the most common mutations in infertile males, where they involve one or more "azoospermia factors" (AZFa, b, and c). Understanding of the AZF structure and gene content and mapping of the deletion breakpoints in infertile men are still incomplete. We have assembled a complete 4.3 Mb map of AZFb and surrounding regions by means of 38 BAC clones. The proximal part of AZFb consists of large repeated sequences organised in palindromes, but most of it is single copy sequence. A number of known and novel genes and gene families map in this interval, and most of them are testis specific or have testis specific transcripts. STS mapping allowed us to identify four severely infertile subjects with a deletion in AZFb with similar breakpoints, therefore suggesting a common deletion mechanism. This deletion includes at least five single copy genes and two duplicated genes, but does not remove the historical AZFb candidate gene RBMY1. These data suggest that other genes in AZFb may have important roles in spermatogenesis. We had no evidence for homologous recombination between large repeats as a possible deletion mechanism, as shown for AZFa and AZFc. However, identical sequences in AZFb and AZFc exist, and this finding could explain deletions found in these regions.
Ferlin
A
A
University of Padova, Department of Medical and Surgical Sciences, Clinica Medica 3, Centre for Male Gamete Cryopreservation, Via Ospedale 105, 35128 Padova, Italy.
Moro
E
E
Rossi
A
A
Dallapiccola
B
B
Foresta
C
C
D019457:Chromosome Breakage / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping / Q000379:methods; D041322:Chromosomes, Human, Y / Q000235:genetics*; D053487:DEAD-box RNA Helicases; D000075364:Deleted in Azoospermia 1 Protein; D023061:Gene Order / Q000235:genetics; D056426:Genetic Loci; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D009845:Oligospermia / Q000235:genetics; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D029589:Seminal Plasma Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D013076:Sperm Count
C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D005819:Genetic Markers; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D011506:Proteins; C501499:RBMY1A1 protein, human; D016601:RNA-Binding Proteins; D029589:Seminal Plasma Proteins; C492034:DDX3Y protein, human; D053487:DEAD-box RNA Helicases