RESUMEN
Male infertility affects about 7% of the general male population. Balanced structural chromosomal rearrangements are observed in 0.4-1.4% of infertile males and are considered as a well-established cause of infertility. However, underlying pathophysiological mechanisms still need to be clarified. A strategy combining standard and high throughput cytogenetic and molecular technologies was applied in order to identify the candidate genes that might be implicated in the spermatogenesis defect in three male carriers of different balanced translocations. Fluorescence in situ hybridization (FISH) and whole-genome paired-end sequencing were used to characterize translocation breakpoints at the molecular level while exome sequencing was performed in order to exclude the presence of any molecular event independent from the chromosomal rearrangement in the patients. All translocation breakpoints were characterized in the three patients. We identified four variants: a position effect on LACTB2 gene in Patient 1, a heterozygous CTDP1 gene disruption in Patient 2, two single-nucleotide variations (SNVs) in DNAH5 gene and a heterozygous 17q12 deletion in Patient 3. The variants identified in this study need further validation to assess their roles in male infertility. This study shows that beside the mechanical effect of structural rearrangement on meiosis, breakpoints could result in additional alterations such as gene disruption or position effect. Moreover, additional SNVs or copy number variations may be fortuitously present and could explain the variable impact of chromosomal rearrangements on spermatogenesis. In conclusion, this study confirms the relevance of combining different cytogenetic and molecular techniques to investigate patients with spermatogenesis disorders and structural rearrangements on genomic scale.
Asunto(s)
Estudios de Asociación Genética/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Infertilidad Masculina/genética , Espermatogénesis/genética , Translocación Genética , Adulto , Astenozoospermia/genética , Dineínas Axonemales/genética , Secuencia de Bases , Puntos de Rotura del Cromosoma , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Fosfoproteínas Fosfatasas/genética , Polimorfismo de Nucleótido Simple , Secuenciación del Exoma , Secuenciación Completa del Genoma , beta-Lactamasas/genéticaRESUMEN
A review concerning the anaerobic baffled reactor (ABR) treating communal wastewater under mesophilic conditions is presented. Existing studies indicate strong resilience of the reactor towards loading variations and shock-loads. The compartmentalisation of the ABR is a strongly stabilising factor with feed fluctuations being evened out across reactor chambers. Significant chemical oxygen demand (COD) reduction occurs almost exclusively in the first three chambers. The hydraulic rather than the organic loading rate is treatment limiting. Laboratory-scale studies show high treatment efficiencies of above 80% COD removal. It was found that most laboratory-scale studies do not factor in important aspects of field operation, such as diurnal fluctuations of feed characteristics, adequate start-up periods and periods of constant loading and optimised chamber outlet design, and never studied the effect of loading on sludge digestion. Performance data on full-scale ABR implementations, however, are extremely scarce, and existing studies are without exception affected by site-specific treatment-limiting factors hindering the extrapolation of generally valid conclusions. In view of a large-scale roll-out, communal ABRs are not sufficiently understood. Current challenges concerning the optimisation of reactor design require numerous well-monitored long-term full-scale reactor investigations. Existing ABR investigations yield encouraging results, supporting that the ABR may be one of the solutions answering the global call for low-maintenance, robust treatment systems.