XXXX gene, a new candidate gene for spermatogenesis failure.

@entity1 @entity71347 @entity4810 @entity6660 @entity2774 @entity3893 @entity4334 @entity3689 @entity71348
INTRODUCTION: Genes involved in testicular differentiation, spermatogenesis, proliferation and apoptosis of germ cells have been shown to evolve rapidly and display rapid DNA changes. These genes are therefore good candidates for explaining impairments in spermatogenesis. Initial studies of some of these genes appear to confirm this hypothesis. The @entity71347 candidate gene belongs to the RHOX family clustered in Xq24 and is specifically expressed in the testis. It contains four exons and codes for a 288 @entity3689 (aa) transcription factor. It has a high degree of homology (>99.9%) with its paralogue @entity71348 , which is also preferentially expressed in the testis. OBJECTIVES: To sequence @entity71347 and @entity71348 in intracytoplasmic sperm injection (ICSI) @entity1 and identify any single- @entity4334 polymorphisms (SNPs) associated with impaired spermatogenesis. MATERIALS: A cohort of 327 @entity1 in ICSI programmes at Poissy and Bichat hospitals. All @entity1 gave their written, informed consent to participation. One hundred @entity1 had unaffected spermatogenesis and 227 displayed impaired spermatogenesis. METHODS: The four exons in each of @entity71347 and @entity71348 were sequenced in 47 @entity1 with @entity6660 or @entity3893 . Given that exons 2 and 3 were found to harbour most of the SNPs, only these two exons were sequenced in the remaining 280 subjects. RESULTS: Due to the extremely high degree of sequence identity between @entity71347 and @entity71348 , we were not able to distinguish between the sequences of these two genes. Although 9 SNPs were identified, there were no significant frequency differences between ICSI @entity1 with normal vs. impaired spermatogenesis. Two insertions were identified: a 21- @entity4334 insertion was retrieved in both groups and a @entity2774 insertion (inducing a premature stop codon) only found in two @entity1 with impaired spermatogenesis. CONCLUSION/OUTLOOK: @entity71347 is a good candidate for rapid evolution by positive selection. Analysis of the polymorphism frequency in exons 2 and 3 did not allow us to correlate the identified SNPs with @entity4810 . However, a single @entity4334 insertion was identified only in @entity1 with impaired spermatogenesis. Further work will be needed to establish whether genetic changes in @entity71347 can give rise to defects in spermatogenesis.
