A5016955998- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Sexual Differentiation and Disorders
- Chromosomal and Genetic Variations
- Forensic and Genetic Research
- Renal and related cancers
- Prenatal Screening and Diagnostics
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Microtubule and mitosis dynamics
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Forensic Anthropology and Bioarchaeology Studies
- Genetic and Kidney Cyst Diseases
- Nutrition, Genetics, and Disease
- Urological Disorders and Treatments
- Hemoglobinopathies and Related Disorders
- Neuroscience of respiration and sleep
- Urologic and reproductive health conditions
- RNA and protein synthesis mechanisms
- Reproductive System and Pregnancy
- Genetic diversity and population structure
- Epigenetics and DNA Methylation
- Yersinia bacterium, plague, ectoparasites research
Universidade do Porto
2016-2025
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2015-2024
Centro de Genética Clínica
2023-2024
IPO Porto
2006-2022
Radboud University Nijmegen
2021
Radboud University Medical Center
2021
University of Cambridge
2010
Abstract De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de an important severe male infertility and explain portion of the genetic causes this understudied disorder. To test hypothesis, we utilize trio-based exome sequencing cohort 185 infertile males their unaffected parents. Following systematic analysis, 29 145 rare (MAF < 0.1%) protein-altering classified as possibly causative phenotype. observed significant...
Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in human population. We hypothesized men spermatogenic impairment, a disease unknown genetic architecture common cause male infertility, are enriched for rare deleterious compared to normal spermatogenesis. After assaying genomewide SNPs CNVs 323 Caucasian idiopathic impairment more than 1,100 controls, we estimate each autosomal deletion detected...
Male 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 58 men with unexplained meiotic and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) M1AP, encoding meiosis 1 associated protein, three unrelated...
P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are short (21 to 35 nucleotides in length) and noncoding found almost exclusively germ cells, where they regulate aberrant expression of transposable elements postmeiotic gene expression. Critical the processing piRNAs is protein poly(A)-specific RNase-like domain containing 1 (PNLDC1), which trims their 3' ends and, when disrupted mice, causes azoospermia male infertility.We performed exome sequencing on DNA samples from 924...
Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining genetic basis NOA has proven challenging, advanced classification subforms not based on genetics, but simple description testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed cases identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes 2-stage burden test with 2072 11,587 fertile controls. The disrupted are...
The Y chromosome of mammals is particularly prone to accumulate genes related male fertility. However, the high rate molecular evolution on this predicts reduced power across-species comparative approach in identifying male-specific that are essential for sperm production humans. We performed a comprehensive analysis expression Y-linked transcripts and their X homologues several human tissues, biopsies infertile patients, an attempt identify new testis-specific involved spermatogenesis....
Abstract The clinal pattern observed for the distribution of Y‐chromosome lineages in Europe is not always reflected at a geographically smaller scale. Six hundred and sixty‐three male samples from 18 administrative districts Portugal were typed 25 biallelic 15 microsatellite markers, order to assess degree substructuring lineage distribution. Haplogroup frequency distributions, Analysis Molecular Variance (AMOVA) genetic distance analyses both Y‐SNP Y‐STR levels revealed general homogeneity...
X monosomic mice (39,XO) have a remarkably mild phenotype when compared to women with Turner syndrome (45,XO). The generally accepted hypothesis explain this discrepancy is that the number of genes on mouse chromosome which escape inactivation, and thus are expressed at higher levels in females, very small. However has never been tested only small assayed for their X-inactivation status mouse. We performed global expression analysis four somatic tissues (brain, liver, kidney muscle) adult...
Abstract STUDY QUESTION Do the genetic determinants of idiopathic severe spermatogenic failure (SPGF) differ between generations? SUMMARY ANSWER Our data support that component SPGF is impacted by dynamic changes in environmental exposures over decades. WHAT IS KNOWN ALREADY The form has a multifactorial etiology wherein an interaction genetic, epigenetic, and factors leads to disease onset progression. At level, genome-wide association studies (GWASs) allow analysis millions variants across...
A efetividade da participação do pai no momento parto ainda é um obstáculo devido a diversos fatores, contribuindo para insegurança e medo paterno nesse processo. É importante construção de estratégias promoção paternidade ativa, como o uso cartilhas educativas. O objetivo geral foi validar uma cartilha educativa sobre ativa durante trabalho parto, os objetivos específicos foram proporcionar validação aparência promover conteúdo parto. Trata-se estudo caráter metodológico. população composta...
Abstract The most severe form of male infertility is idiopathic non-obstructive azoospermia (NOA), a complete sperm absence in the ejaculate. We performed exome sequencing Croatian infertile brothers with NOA and found variant DMRT1 (Doublesex mab-3 related transcription factor 1) gene that was further assessed by EMSA assay molecular dynamic simulations. additionally screened for mutations 1940 men diagnosed spermatogenic failure, 644 normozoospermic controls, 105 females primary ovarian...
Human hemoglobins, the oxygen carriers in blood, are composed by two α-like and β-like globin monomers. The β-globin gene cluster located at 11p15.5 comprises one pseudogene five genes whose expression undergoes critical switches: embryonic-to-fetal fetal-to-adult transition. HBD encodes δ-globin chain of minor adult hemoglobin (HbA2), which is assumed to be physiologically irrelevant. Paradoxically, reduced diversity levels have been reported for this gene. In study, we sought a detailed...
With the aid of novel and powerful molecular biology techniques, recent years have witnessed a dramatic increase in number studies reporting involvement complex structural variants several genomic disorders. In fact, with discovery Copy Number Variants (CNVs) other forms unbalanced variation, much attention has been directed to detection characterization such rearrangements, as well identification mechanisms involved their formation. However, it long appreciated that chromosomes can undergo...
The double sex and mab-3-related transcription factor 1 (DMRT1) gene has long been linked to sex-determining pathways across vertebrates is known play an essential role in gonadal development maintenance of spermatogenesis mice. In humans, the genomic region harboring DMRT cluster implicated disorders recently DMRT1 deletions were shown be associated with non-obstructive azoospermia (NOA). this work, we have employed different methods screen a cohort Portuguese NOA patients for exonic...
What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing (ES) patients with non-obstructive azoospermia (NOA)?One 28 NOA cases carried an identifiable, medically actionable SF.In addition to molecular diagnostics, ES allows assessment clinically disease-related gene variants that are not connected patient's primary diagnosis, but knowledge which may allow prevention, delay or amelioration late-onset monogenic conditions. Data on SFs...
The transition zone is a specialised gate at the base of cilia/flagella, which separates ciliary compartment from cytoplasm and strictly regulates protein entry. We identified potential new regulator male germ cell zone, CEP76. demonstrated that CEP76 was involved in selective entry incorporation key proteins required for sperm function fertility into ultimately tail. In mutant, tails were shorter immotile as consequence deficits essential motility including DNAH2 AKAP4, accumulated neck...
Abstract Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm ejaculates, we identified damaging variants the dynein-related gene AXDND1 . We thus hypothesised that is a regulator male fertility. To test this hypothesis, produced knockout mouse model. Axdnd1 −/− males were sterile at all ages but presented an...