25 documents found, page 1 of 3
A genetic variant in the 3′-UTR of PIWIL4 confers risk for extreme phenotypes o...
González-Muñoz, Sara; Cerván Martín, Miriam; Guzmán-Jiménez, Andrea; Rodríguez-Martín, Ana Isabel; Garrido, Nicolás; Castilla, José A.Funding Information: This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (grant: PID2020-120157RB-I00 funded by MICIU/AEI/10.13039/501100011033; and grant: PID2023-152215OB-I00 funded by MICIU/AEI/10.13039/501100011033 and ERDF, EU). M.C.-M is beneficiary of a Juan de la Cierva 2022 postdoctoral fel...
Changes in environmental exposures over decades may influence the genetic archi...
Cerván-Martín, Miriam; González-Muñoz, Sara; Guzmán-Jiménez, Andrea; Higueras-Serrano, Inmaculada; Castilla, José A.; Garrido, Nicolás; Luján, SaturninoStudy question: Do the genetic determinants of idiopathic severe spermatogenic failure (SPGF) differ between generations? Summary answer: Our data support that the genetic component of idiopathic SPGF is impacted by dynamic changes in environmental exposures over decades. What is known already: The idiopathic form of SPGF has a multifactorial etiology wherein an interaction between genetic, epigenetic, and envi...
Contribution of TEX15 genetic variants to the risk of developing severe non-obs...
Guzmán-Jiménez, Andrea; González-Muñoz, Sara; Cerván-Martín, Miriam; Rivera-Egea, Rocío; Garrido, Nicolás; Luján, Saturnino; Santos-Ribeiro, SamuelBackground: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition...
Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Se...
Cerván-Martín, Miriam; Bossini-Castillo, Lara; Guzmán-Jimenez, Andrea; Rivera-Egea, Rocío; Garrido, Nicolás; Luján, Saturnino; Romeu, GemaWe aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood-testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs228783...
A de novo paradigm for male infertility
Oud, M.S.; Smits, R.M.; Smith, H.E.; Mastrorosa, F.K.; Holt, G.S.; Houston, B.J.; de Vries, P.F.; Alobaidi, B.K.S.; Batty, L.E.; Ismail, H.De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic an...
Common genetic variation in KATNAL1 non-coding regions is involved in the susce...
Cerván‐Martín, Miriam; Bossini‐Castillo, Lara; Guzmán‐Jiménez, Andrea; Rivera‐Egea, Rocío; Garrido, Nicolás; Lujan, Saturnino; Romeu, GemaBackground: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single nucleotide polymorphisms in the development of male infertility as a consequence of seve...
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...
Actionable secondary findings following exome sequencing of 836 non-obstructive...
Kasak, Laura; Lillepea, Kristiina; Nagirnaja, Liina; Aston, Kenneth I.; Schlegel, Peter N.; Gonçalves, João; Carvalho, Filipa; Moreno-Mendoza, DanielStudy question: What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing (ES) of patients with non-obstructive azoospermia (NOA)? Summary answer: One in 28 NOA cases carried an identifiable, medically actionable SF. What is known already: In addition to molecular diagnostics, ES allows assessment of clinically actionable disease-related gene variants tha...
Common genetic variation in KATNAL1 non‐coding regions is involved in the susce...
Cerván‐Martín, Miriam; Bossini‐Castillo, Lara; Guzmán‐Jiménez, Andrea; Rivera‐Egea, Rocío; Garrido, Nicolás; Lujan, Saturnino; Romeu, GemaBackground: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of seve...
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...