7 documents found, page 1 of 1
Diverse monogenic subforms of human spermatogenic failure
Nagirnaja, Liina; Lopes, Alexandra M.; Charng, Wu-Lin; Miller, Brian; Stakaitis, Rytis; Golubickaite, Ieva; Stendahl, Alexandra; Luan, TianpengchengNon-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven chal lenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause i...
Immune and spermatogenesis-related loci are involved in the development of extr...
Cerván-Martín, Miriam; Tüttelmann, Frank; Lopes, Alexandra M.; Bossini-Castillo, Lara; Rivera-Egea, Rocío; Garrido, Nicolás; Lujan, SaturninoWe conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, name...
New insight into the genetic contribution of common variants to the development...
Cerván-Martín, Miriam; Tüttelmann, Frank; Lopes, Alexandra; Castillo, Lara B.; Garrido, Nicolás; Luján, Saturnino; Castilla, José A.; Azoonomic, S.G.Study question: What is the contribution of the common genetic variation to the development of unexplained male infertility due to severe spermatogenic failure (SPGF)? Summary answer: Genetic polymorphisms of key immune and spermatogenesis loci are involved in the etiology of the most severe SPGF cases, defined by Sertoli cell-only (SCO) phenotype. What is known already: Male infertility is a rising worldwide c...
Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men w...
Hardy, Jimmaline J.; Wyrwoll, Margot J.; Mcfadden, William; Malcher, Agnieszka; Rotte, Nadja; Pollock, Nijole C.; Munyoki, Sarah; Veroli, Maria V.Male infertility impacts millions of couples yet, the etiology of primary infertility remains largely unknown. A critical element of successful spermatogenesis is maintenance of genome integrity. Here, we present a genomic study of spermatogenic failure (SPGF). Our initial analysis (n=176) did not reveal known gene-candidates but identifed a potentially signifcant single-nucleotide variant (SNV) in X-linked ger...
Disruption of human meiotic telomere complex genes TERB1, TERB2 and MAJIN in me...
Salas-Huetos, Albert; Tüttelmann, Frank; Wyrwoll, Margot J.; Kliesch, Sabine; Lopes, Alexandra M.; Gonçalves, João; Boyden, Steven E.; Wöste, MariusNon-obstructive azoospermia (NOA), the lack of spermatozoa in semen due to impaired spermatogenesis affects nearly 1% of men. In about half of cases, an underlying cause for NOA cannot be identified. This study aimed to identify novel variants associated with idiopathic NOA. We identified a nonconsanguineous family in which multiple sons displayed the NOA phenotype. We performed whole-exome sequencing in three ...
Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severel...
Wyrwoll, Margot J.; Temel, Şehime G.; Nagirnaja, Liina; Oud, Manon S.; Lopes, Alexandra M.; van der Heijden, Godfried W.; Heald, James S.; Rotte, NadjaMale infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant...
Spectral features of nuclear DNA in human sperm assessed by Raman Microspectros...
Da Costa, Raul; Amaral, Sandra; Redmann, Klaus; Kliesch, Sabine; Schlatt, StefanRaman Microspectroscopy represents an innovative tool for the assessment of sperm biochemical features otherwise undetectable by routine semen analysis. Previously, it was shown that induced DNA damage can be detected in smeared sperm by this technique. This novel readout may be of value for clinical settings especially if it can be transferred to living cells. Yet, starting with living sperms this study was ca...