Institut für Humangenetik
Refine
Is part of the Bibliography
- yes (234)
Year of publication
Document Type
- Journal article (124)
- Doctoral Thesis (109)
- Book (1)
Keywords
- Fanconi-Anämie (13)
- Molekulargenetik (10)
- DNA methylation (9)
- Fanconi Anämie (9)
- DNS-Reparatur (8)
- Erbkrankheit (8)
- Epigenetik (7)
- Brustkrebs (6)
- Fanconi anemia (6)
- Mutation (6)
- breast cancer (6)
- BRCA1 (5)
- DNA repair (5)
- Genetik (5)
- Genmutation (5)
- genetics (5)
- heterochromatin (5)
- mutations (5)
- ovarian cancer (5)
- spectral karyotyping (5)
- Altern (4)
- Anura (4)
- BMD (4)
- Fanconi Anemia (4)
- Humangenetik (4)
- Makuladegeneration (4)
- Methylierung (4)
- Muskeldystrophie (4)
- Netzhaut (4)
- Zellzyklus (4)
- cancer (4)
- consortium (4)
- epigenetics (4)
- gene (4)
- mutation (4)
- sex chromosomes (4)
- zebrafish (4)
- 5-Methylcytosine (3)
- B chromosomes (3)
- DMD (3)
- Duchenne-Syndrom (3)
- Durchflusszytometrie (3)
- FISH (3)
- FSHD (3)
- Fanconi Anaemia (3)
- Genanalyse (3)
- Hereditäres Angioödem (3)
- Hämophilie A (3)
- Medizin (3)
- VKORC1 (3)
- VMD2 (3)
- Vitamin K (3)
- duchenne muscular dystrophy (3)
- fanconi anemia (3)
- genetic modifiers (3)
- genome-wide association (3)
- immunofluorescence (3)
- investigators (3)
- methylation (3)
- mosaicism (3)
- next generation sequencing (3)
- screening (3)
- sperm (3)
- susceptibility loci (3)
- whole exome sequencing (3)
- 2B (2)
- 5-Azadeoxycytidin (2)
- 5-azadeoxycytidine micronucleus (2)
- ADHD (2)
- AMD (2)
- Angiogenese (2)
- BRCA2 (2)
- C1-Inhibitor (2)
- Candida albicans (2)
- Chromosomenverlust (2)
- Cytogenetik (2)
- DM2 (2)
- DNA (2)
- DNA Reparatur (2)
- DNA-Repair (2)
- DNA-Reparatur (2)
- DNA-Reparaturgene (2)
- Duchenne (2)
- Duchenne muscular dystrophy (2)
- Eierstockkrebs (2)
- Epigenetics (2)
- Exomsequenzierung (2)
- Fabry disease (2)
- Fabry genotype (2)
- Fabry phenotype (2)
- Gen (2)
- Gentherapie (2)
- Geschlechtschromosomen (2)
- Gliedergürtelmuskeldystrophie (2)
- HAE (2)
- HPP (2)
- Hypophosphatasie (2)
- Hämophilie (2)
- Hörstörung (2)
- Ionisierende Strahlung (2)
- Keimzellmosaik (2)
- Konsanguinität (2)
- Maus (2)
- Mausmodell (2)
- Mikronukleus (2)
- Mitomycin C (2)
- Molekularbiologie (2)
- Morbus Best (2)
- Mosaik (2)
- Mosaizismus (2)
- Mutationsanalyse (2)
- Mutationsraten (2)
- Next generation sequencing (2)
- PCR (2)
- Positionsklonierung (2)
- Progeria adultorum (2)
- Proteine (2)
- RAD51C (2)
- RPE (2)
- Retinoschisis (2)
- Reversion (2)
- SLX4 (2)
- STR profile (2)
- Screening (2)
- Spermium (2)
- TNAP (2)
- VKORC1L1 (2)
- Vitamin-K-Gruppe (2)
- Warfarin (2)
- Würzburg / Institut für Humangenetik (2)
- Zellzyklusanalyse (2)
- ageing (2)
- angiogenesis (2)
- association (2)
- bisulfite pyrosequencing (2)
- blood (2)
- cardiogenetics (2)
- case report (2)
- cell cycle analysis (2)
- chromosome loss (2)
- common variants (2)
- congenital myopathy (2)
- copy number variation (2)
- cytogenetics (2)
- deafness (2)
- degeneration (2)
- diagnosis (2)
- disease genetics (2)
- exome sequencing (2)
- extracellular matrix (2)
- fetal programming (2)
- fibrosis (2)
- flow cytometry (2)
- flowcytometry (2)
- gene therapy (2)
- genetic diagnostics (2)
- genetic heterogeneity (2)
- genome (2)
- genomic imprinting (2)
- genotype-phenotype correlation (2)
- gestational diabetes mellitus (2)
- gridle muscular-dystrophy (2)
- growth hormone deficiency (2)
- hearing impairment (2)
- hearing loss (2)
- hemophilia (2)
- hepatic stellate cell (2)
- hereditary angioedema (2)
- hereditary breast and ovarian cancer (2)
- hypophosphatasia (2)
- immunodeficiency (2)
- incidence (2)
- intellectual disability (2)
- liver (2)
- macular degeneration (2)
- microcephaly (2)
- mineralization (2)
- modifiers (2)
- mouse model (2)
- myofibrillar myopathy (2)
- myofibroblast (2)
- myopathy (2)
- nervous system (2)
- next generation sequencing (NGS) (2)
- positional cloning (2)
- protein (2)
- recombination (2)
- retina (2)
- risk (2)
- sensory neuropathy (2)
- single-nucleotide polymorphisms (2)
- skeletal dysplasia (2)
- somatic mosaicism (2)
- sperm DNA methylation (2)
- survival (2)
- variants (2)
- vitamin K (2)
- whole-exome sequencing (2)
- (classical and atypical) Werner syndrome (1)
- - (1)
- 16q22 (1)
- 3D modeling (1)
- 3R (1)
- 5-methylcytosine (1)
- A chromosomes (1)
- AFLP (1)
- AKT-signaling (1)
- ALPL (1)
- ART outcome (1)
- ATM (1)
- ATM gene (1)
- Achondroplasie (1)
- Adulthood (1)
- Age-related macular degeneration (1)
- Alburnus alburnus (1)
- Alkalische Phosphatase (1)
- Allelfrequenzen (1)
- Allgemeinmedizin (1)
- Allophrynidae (1)
- Alter (1)
- Alternatives Spleißen (1)
- Alzheimer's disease (1)
- Alzheimerkrankheit (1)
- Anticoagulants (1)
- Antralfollikel (1)
- Apolipoprotein (1)
- Array-Methoden (1)
- Arrhythmie (1)
- Asisted Reproduction (1)
- Aspergillus fumigatus (1)
- Assoziation (1)
- Ataxia telangiectasia (1)
- Ataxia telangiectasia (AT) (1)
- Ataxia teleangiectatica (1)
- Autism (1)
- Autism spectrum disorders (1)
- Autismus (1)
- B Chromosomen (1)
- B-Chromosom (1)
- B4GALT7 gene (1)
- BRCA1/2 (1)
- BRIP1 gene (1)
- Becker (1)
- Becker-Kiener-Syndrom (1)
- Berechnung (1)
- Best Disease (1)
- Best's Disease (1)
- Best-Krankheit (1)
- Bioinformatics (1)
- Blasentumor (1)
- Blutgefäß (1)
- Blutgerinnung (1)
- Brachmann-de-Lange-Syndrom (1)
- Brachmann-de-Lange-syndrome (1)
- BrdU replication banding pattern (1)
- BrdU/dT replication banding (1)
- Breastcancer (1)
- Brüder Grimm (1)
- C1 Inhibitor (1)
- C1-INH (1)
- C1-inhibitor (1)
- C1INH (1)
- C282Y (1)
- CAGSSS (1)
- CCM (1)
- CCM1/Krit1 (1)
- CCM2/Malcavernin (1)
- CCM3 (1)
- CCM3/PDCD10 (1)
- CDC14A (1)
- CIN (1)
- CLRN2 (1)
- CNV (1)
- COVID-19 (1)
- CRISPR-Cas Systems (1)
- CRISPR/Cas9 (1)
- Calcyon (1)
- Carcinogenese (1)
- Caretaker gene syndromes (1)
- Caretaker-Gen-Syndrome (1)
- Cathepsin (1)
- Cellcycle (1)
- Cellcycle blockage (1)
- Central Core Disease (1)
- Centrolenidae (1)
- Charcot-Marie-Tooth neuropathy 1A (1)
- Checkpoints (1)
- Chromosomal instability (1)
- Chromosomenaberration (1)
- Chromosomenaberrationen (1)
- Chromosomenbruch (1)
- Chromosomenbruchanalyse (1)
- Chromosomenbruchsyndrome (1)
- Chromosomeninstabilitätssyndrome (1)
- Chromosomenkondensation (1)
- Coagulation factor IX (1)
- Coexpression (1)
- Cognitive control (1)
- Copy number variation (1)
- Cornelia-de-Lange-Syndrom (1)
- Cornelia-de-Lange-syndrome (1)
- Cortex (1)
- Coumarin (1)
- Cranial sutures (1)
- Craniosynostosis (1)
- Creatin Kinase (1)
- Cyrillic 2.13 (1)
- D4Z4 partial deletion (1)
- DFNB32 (1)
- DFNB68 (1)
- DLX5/6 (1)
- DM1 (1)
- DNA Methylation (1)
- DNA damage (1)
- DNA damage response (1)
- DNA double-strand break (1)
- DNA methylation dynamics (1)
- DNA methyltransferase gene (1)
- DNA purification (1)
- DNA repair defect (1)
- DNA repair gene (1)
- DNA repair genes (1)
- DNA sequencing (1)
- DNA-Instabilitätssyndrom (1)
- DNA-Methylation (1)
- DNA-Methylierung (1)
- DNA-Quervernetzung (1)
- DNA-Sequenz (1)
- DNA-repair (1)
- DNA-repair genes (1)
- DNER (1)
- DNMT3B (1)
- DNS-Methyltransferase (1)
- DYNC1I1 (1)
- Damage (1)
- Deflazacort (1)
- Degeneration (1)
- Deletion <Genetik> (1)
- Deutschland (1)
- Deutschland / Stammzellgesetz (1)
- Development (1)
- Diagnostik (1)
- Dickdarmkrebs (1)
- Domäne <Biochemie> (1)
- Down Syndrom (1)
- Down syndrome (1)
- Down´s Syndrome (1)
- Duchenne dystrphy (1)
- Duchennesche Muskeldystrophie (1)
- Duchflußzytophotometrie (1)
- Durchflusscytometrie (1)
- Durchflußzytometrie (1)
- Dystrophin Gene (1)
- Dystrophin-Gen (1)
- ENaC (1)
- ERCC1-XPF (1)
- ERCC4 (1)
- EU (1)
- Embryos (1)
- Endothelzelle (1)
- Endothelzellen (1)
- Enhancer elements (1)
- Entwicklung (1)
- Environment (1)
- Epigenetische Uhr (1)
- Epigenotypus (1)
- Epimutation (1)
- Epimutationen (1)
- Erbkrankheiten (1)
- Erfolg (1)
- Erkrankungswahrscheinlcihkeit (1)
- Erwachsener (1)
- Evans syndrome (1)
- Excelsior Cyrillic (1)
- Extracellular matrix (1)
- FA (1)
- FAAP100 (1)
- FADS1 (1)
- FADS2 (1)
- FADS3 (1)
- FANCA (1)
- FANCD2 (1)
- FANCO (1)
- FANCP (1)
- FAP-1/PTPN13 (1)
- Fabry (1)
- Fabry-Krankheit (1)
- Fallbeispiele (1)
- Familial Beckwith-Wiedemann syndrome (1)
- Familial breast cancer (1)
- Familienanamnese (1)
- Familiärer Brustkrebs (1)
- Fanconi Anämie (FA) (1)
- Fanconi Anämie A (1)
- Fanconi anaemia (1)
- Fanconi anemia (FA) (1)
- Fanconi anemia A (1)
- Fanconi-anemia subtype (1)
- Fetal brain development (1)
- Fetale Programmierung (1)
- Fettsäuredesaturasen (1)
- Fluorescence in situ hybridization (1)
- Fluorescence-in-situ-hybridization (1)
- Fluoreszenz-in-situ-Hybridisierung (1)
- Fourthcorner analysis (1)
- Frequency (1)
- Frontal cortex (1)
- Fruchtwasserzellen (1)
- Frühgeburt (1)
- Förderung (1)
- G0/G1 (1)
- G2 Phase (1)
- GTL2 (1)
- Gamma-Carboxylase (1)
- Gecko (1)
- Gefäßkrankheit (1)
- Gehirn (1)
- Gen BRCA 1 (1)
- Gen BRCA 2 (1)
- Gendefekt (1)
- Gene-expression (1)
- Genes (1)
- Genetische Variabilität (1)
- Genetisches Imprinting (1)
- Genetisches Modell (1)
- Genom (1)
- Genome (1)
- Genort (1)
- Genotyp (1)
- Genotyp-Phänotyp Korrelation (1)
- Genotype-phenotype association (1)
- Genotype–phenotype correlations (1)
- Genotypisierung (1)
- Genpanel (1)
- Genregulation (1)
- Gerinnungsfaktor VIII (1)
- Gesundheitsstatus (1)
- Gesundheitssystem (1)
- Gewebe-unspezifische Alkalische Phosphatase (1)
- Glaukom (1)
- H63D (1)
- Hereditary Angioedem (1)
- Hereditary breast cancer (1)
- Herzmuskelkrankheit (1)
- High throughput screening (1)
- High-throughput data (1)
- Hindbrain (1)
- Histologic grade (1)
- Holliday junction reolvass (1)
- Holstein <Rind> (1)
- Human genetics (1)
- Human prefrontal cortex (1)
- Hypermutabilität (1)
- Hypophosphatasia (1)
- Hämatopoese (1)
- Hämochromatose (1)
- Hörstörungen (1)
- IARS2 (1)
- ICF2 (1)
- ICL (1)
- ICSI (1)
- IGF2-H19 (1)
- II citrullinemia (1)
- IMSI (1)
- Immunfluoreszenz (1)
- Imprinting (1)
- Indian muntjac (1)
- Induced Pluripotent Stem Cells (1)
- Infertilität (1)
- Informationsweitergabe (1)
- Instability (1)
- Instabilität (1)
- Inzidenz <Medizin> (1)
- Inzidenzschätzung (1)
- Jugendliche und erwachsene Probanden (1)
- KRAS (1)
- Kandidatengen (1)
- Kasuistik (1)
- Kathepsin (1)
- Kathepsin B (1)
- Kathepsin L (1)
- Kavernom (1)
- Keimzell- und Embryonalentwicklung (1)
- Knochenmarksversagen (1)
- Koagulopathie (1)
- Kolorektales Karzinom (1)
- Koppelungsanalyse (1)
- Korrelation (1)
- Kraniosynostosen (1)
- Krebserkrankungen (1)
- LGMDR5 (1)
- Landouzy-Déjerine-Atrophie (1)
- Langdon Down (1)
- Lautwahrnehmung (1)
- Legasthenie (1)
- Lese-Rechtschreibstörung (1)
- Limb development (1)
- Limb girdle muscular dystrophy (LGMD) (1)
- Long-term follow-up (1)
- MCPH1 (1)
- MEK/ERK-signaling (1)
- MFM (1)
- MPP4 (1)
- MPP5 (1)
- MTM (1)
- Makula (1)
- Makuladystrophie (1)
- Male breast cancer (1)
- Malignant Hyperthermia (1)
- Malignant neoplasms (1)
- Maligne Hyperthermie (1)
- Massive parallele Sequenzierung (1)
- Medizinisches Versorgungszentrum (1)
- Meiose (1)
- Membranproteine (1)
- Mensch (1)
- Mentale Retardierung (1)
- Methylome (1)
- Microarray (1)
- Microarray analysis (1)
- Microdeletions (1)
- Mikroarray (1)
- Mikrodeletionen (1)
- Mikrozephalie (1)
- Missbildung (1)
- Miyoshi myopathy (1)
- Molecular approaches (1)
- Monogen (1)
- Morbidität (1)
- Mortalität (1)
- Mucopolysaccharidosis IIIa (1)
- Muenke-Syndrom (1)
- Multiple displacement amplification (1)
- Multiproteinkomplex (1)
- Multivariate analysis (1)
- Muscular Dystrophy (1)
- Muskeldystrophie Becker (1)
- Muskeldystrophie Duchenne (1)
- Muskelentwicklung (1)
- Muskelkrankheit (1)
- Mutationen (1)
- Mutationrate (1)
- Mutationsrate (1)
- Mutationswahrscheinlichkeit (1)
- Myotone Dystrophie (1)
- Myotone Dystrophy (1)
- Myotonische Dystrophie (1)
- Myotubular Myopathy (1)
- Myotubuläre Myopathie (1)
- N170 (1)
- NEIL2 (1)
- NLS-Sequenz (1)
- Na-K-ATPase (1)
- Nachtblindheit (1)
- Neanderthal (1)
- Neisseria meningitidis (1)
- Nervendegeneration (1)
- Netzhautdegeneration (1)
- Neue Fanconi Anämie Gene (1)
- Neurodegeneration (1)
- Neuroepigenomics (1)
- Neuromuskuläre Erkrankungen (1)
- Neuromuskuläre Krankheit (1)
- Neurons (1)
- Next Generation Sequencing (1)
- Next Generation Sequencing (NGS) (1)
- Next-Generation Sequencing (1)
- Nibrin (1)
- Nijmegen Breakage Syndrom (1)
- Nijmegen Breakage Syndrom (NBS) (1)
- Nijmegen breakage syndrome (1)
- Nijmegen breakage syndrome (NBS) (1)
- Nonsensmutation (1)
- North Carolina Makuladystrophie (1)
- North Carolina Makuladystrophy (1)
- OGG1 (1)
- Oogenese (1)
- Oozyte (1)
- Ordination methods (1)
- Organisationsform (1)
- Ovarian (1)
- Ovariancancer (1)
- Ovarielle Alterung (1)
- P100 (1)
- PCC-Syndrom (1)
- PDZ domain (1)
- PROMM (1)
- PSD95 (1)
- Pakistan (1)
- Pankreaskarzinom (1)
- Parameter (1)
- Parameter <Mathematik> (1)
- Parent-of-origin (1)
- Paternal age effect (1)
- Pathology (1)
- Patterns (1)
- Penetranz (1)
- Pfeiffer-Syndrom (1)
- Phi29 Polymerase (1)
- Phänotyp (1)
- Phänotypische Heterogenität (1)
- Pigmentepithel (1)
- Plasma DNA (1)
- Pompe disease (1)
- Postovulatorische Alterung (1)
- Prenatal diagnosis (1)
- Primary Microcephaly (1)
- Primary care (1)
- Proteininteraktion (1)
- Proteomanalyse (1)
- Proximale myotone Myopathie (1)
- Pränataldiagnostik (1)
- Pränatale Diagnostik (1)
- Psychosoziale Beratung (1)
- Psychosoziale Situation (1)
- Punktmutation (1)
- Qualitätskontrolle (1)
- RAD50-Defizienz (1)
- RAD52 (1)
- RLQ analysis (1)
- RNA metabolism (1)
- RNA-Seq analysis (1)
- RPE specific genes (1)
- Rab14 (1)
- Radiosensitivität (1)
- Radiäre Drusen (1)
- Rechenprogramme (1)
- Regeneration (1)
- Rekombination (1)
- Remission (1)
- Renal abnormalities (1)
- Repair (1)
- Reproduktionsmedizin (1)
- Retina (1)
- Ribbon-Synapse (1)
- Risiko (1)
- Risikoberatung (1)
- Risikoberechnung (1)
- Risikoberechnungen (1)
- Risikofaktoren (1)
- Risk estimation (1)
- Robertsonian translocation chromosomes (1)
- Robertsonsche Translokation (1)
- Robin-Syndrom (1)
- Ryanodin-Rezeptor Gen (1)
- Ryanodine receptor gene (1)
- Ryr 1 (1)
- S1PR2 (1)
- SARS-CoV-2 (1)
- SH3 domain (1)
- SHFM (1)
- SKY analysis (1)
- SLC2A3 (1)
- SMA (1)
- SMN1-Kopien (1)
- SMN1-copies (1)
- SNP array (1)
- SNP-Array (1)
- SNP-microarray (1)
- SOX9 (1)
- STK25/SOK-1/YSK-1 (1)
- Sanger Sequenzierung (1)
- Sanger sequencing (1)
- Schizophrenia (1)
- Schwangerschaft (1)
- Schwangerschaftsdiabetes (1)
- Segregation (1)
- Selective attention (1)
- Self-renewal (1)
- Senile Makuladegeneration (1)
- Senile Makuladegeneration / Pigmentepithel / Genexpression (1)
- Sequenzdaten (1)
- Serpin (1)
- Skull (1)
- Somites (1)
- Spectral Karyotyping (1)
- Spermatogenese (1)
- Spermien (1)
- Spinale Muskelatrophie (1)
- Stability (1)
- Stammzelltransplantation (1)
- Staphylococcus aureus (1)
- Sterilität (1)
- Strahleninduzierte Genominstabilität (1)
- Strahlensensitivität (1)
- Suicidal behavior (1)
- Summe G2/GF (1)
- Susceptibility (1)
- TMEM43 (1)
- TRIM32 (1)
- TYPE-2 (1)
- Terminal 4q deletion syndrome (1)
- Th17 (1)
- Thrombozytopenie (1)
- Tight junction (1)
- Tissue Nonspecific Alkaline Phosphatase (1)
- Tnap (1)
- Transcription (1)
- Transcription regulation (1)
- Transcriptome (1)
- Transcriptomics (1)
- Transkription <Genetik> (1)
- Transkriptome (1)
- Tregs (1)
- Trisomie 21 (1)
- Trisomy 21 (1)
- UBZ (1)
- Ukelei (1)
- Ungarn (1)
- Urodela (1)
- Usher syndrome (1)
- VKCFD (1)
- Vater (1)
- Vektoren (1)
- Verteilung (1)
- Verwandtenehe (1)
- Visualization (1)
- Vitamin K epoxide reductase (1)
- Vitamin-K-Epoxid-Reduktase (1)
- Väterliches Alter (1)
- WDR62 mutation (1)
- Wachstumshormonmangel (1)
- Whole Genome Amplification (1)
- Working memory (1)
- X chromosome (1)
- X-Chromosom (1)
- X-Inaktivierung (1)
- X-chromosomal inactivation (1)
- X-gebundene juvenile Retinoschisis (1)
- X-linked juvenile retinoschisis (1)
- X. laevis-type karyotype (1)
- X. tropicalis-type karyotype (1)
- Xenopus (1)
- Xenopus laevis (1)
- Xenopus tropicalis (1)
- Y chromosome degeneration (1)
- ZBTB24 (1)
- ZBTB24 mutations (1)
- ZNF365 (1)
- ZW sex chromosomes (1)
- Zahnentwicklung (1)
- Zebrabärbling (1)
- Zebrafish (1)
- Zellkern (1)
- Zellkultur (1)
- Zellzyklus-Analyse (1)
- Zellzyklusdiagnostik (1)
- Zellzykluseffekte (1)
- Zentralfibrillen-Myopathie (1)
- Zytogenetik (1)
- abnormalities (1)
- adenoma (1)
- adrenal insufficiency (1)
- age (1)
- age at onset (1)
- age-related (1)
- age-related differentially methylated regions (ageDMRs) (1)
- aldehydes (1)
- allelefrequences (1)
- alleles (1)
- allopolyploidy (1)
- alternative methods (1)
- alternative splicing (1)
- altersabhängig (1)
- alu elements (1)
- alzheimers disease (1)
- amniotic fluid cells (1)
- amphiphysin-2 BIN1 (1)
- amplicon sequencing (1)
- antidepressants (1)
- anxiety disorders (1)
- apoptosis (1)
- array-CGH (1)
- arrhythmogenic cardiomyopathy (1)
- asexual reproduction (1)
- assistierte Reproduktion (1)
- ataxia telangiectasia (1)
- autism (1)
- autophagy (1)
- autopolyploidy (1)
- autosomal dominant (1)
- autosomal recessive (1)
- autosomal recessive hearing loss (1)
- autosomal recessive heredity (1)
- autosomal recessive non-synstromic hearing loss (1)
- autosomal rezessiver Erbgang (1)
- autosomal-dominant (1)
- autosomal-rezessiv (1)
- banding analyses (1)
- bcl-2 associated athanogene protein 3 (1)
- becker muscular dystrophy (1)
- behavior (1)
- bestrophin (1)
- bioinformatics and computational biology (1)
- bivariate Durchflußzytometrie (1)
- bleding disorders other than hemophilia (1)
- blood coagulation (1)
- bone development (1)
- bone marrow failure syndrome (1)
- bone-marrow failure (1)
- bovine (1)
- breakage (1)
- breast cancer predisposition genes (1)
- breast neoplasms (1)
- brothers grimm (1)
- cDNA Selektion (1)
- cDNA selection (1)
- cadherins (1)
- calculation (1)
- cancer treatment (1)
- candida genome database (1)
- candidate genes (1)
- cardiomyopathy (1)
- case reports (1)
- cataracts (1)
- cavernoma (1)
- cell (1)
- cell culture (1)
- cell cycle (1)
- cell cycle studies (1)
- cell death (1)
- cell division (1)
- cell wall (1)
- cellcycle (1)
- cellcycle effects (1)
- centromeric instability (1)
- childhood ataxia (1)
- childhood cancer (1)
- children (1)
- chip-seq (1)
- chromosomal aberrations (1)
- chromosomal abnormality (1)
- chromosomal breakage (1)
- chromosomal instability (1)
- chromosomal instability disorder (1)
- chromosomale Instabilität (1)
- chromosome (1)
- chromosome aberration (1)
- chromosome condensation (1)
- chromosome evolution (1)
- chromosome inversion (1)
- chromosome staining (1)
- chromsomal instability (1)
- classification (1)
- colorectal cancer (1)
- combined retinal dystrophy (1)
- comparative genomics (1)
- complex chromosome rearrangements (1)
- complex disorders (1)
- complex traits (1)
- computational prediction (1)
- congenital (1)
- congenital heart-deffects (1)
- connective tissue disorder (1)
- consanguinity (1)
- copy-number variation (1)
- coumarin (1)
- craniosynostosis (1)
- cross-link repair (1)
- cytokinesis (1)
- cytometrie (1)
- cytotoxicity (1)
- damage (1)
- danazol (1)
- danio rerio (1)
- database (1)
- deep bisulfite sequencing (1)
- deficiency (1)
- deletion (1)
- department of human genetics (1)
- design (1)
- development (1)
- developmental origins hypothesis (1)
- diagnostic delay (1)
- differentially methylated region (1)
- differentiation (1)
- diploidization (1)
- disease (1)
- disruption project (1)
- double trouble (1)
- double-strand DNA breaks (1)
- duplication (1)
- duplication-deficiency (1)
- dysferlinopathy (1)
- dyslexia (1)
- dystrophin (1)
- eExons (1)
- early respiratory-failure (1)
- elective surgery (1)
- elements (1)
- embryos (1)
- emotional disorders (1)
- endonuclease (1)
- endothelial cells (1)
- epigenetic heterogeneity (1)
- epimutation (1)
- epithelial cells (1)
- erblicher Brustkrebs (1)
- establishment (1)
- etiology (1)
- euchromatin (1)
- evolutionary biology (1)
- evolutionary fixation (1)
- expansion (1)
- expression signature (1)
- extreme phenotypes (1)
- facial anomalies (1)
- facio-scapulo-humeral dystrophie (1)
- facio-scapulo-humeralen Muskeldystrophie (1)
- facioscapulohumeral muscular dystrophy (1)
- factor VIII (1)
- familial breast cancer (1)
- families (1)
- family history of glaucoma (1)
- fanconi anaemia (1)
- fanconi-anemia (1)
- fatty acid desaturases (1)
- features (1)
- female (1)
- female Fabry patients (1)
- fetal brain development (1)
- fetal cord blood (1)
- fetal overnutrition (1)
- fibroblasts (1)
- filamin C (1)
- fine-scale mapping (1)
- fish (1)
- flies (1)
- flow (1)
- flow-cytometry (1)
- frameshift (1)
- frontal cortex (1)
- früher vorzeitiger Blasensprung (1)
- functional analysis (1)
- functional modules (1)
- g2 phase (1)
- gamma-carboxylation (1)
- geckos (1)
- gene defect (1)
- gene mutations (1)
- gene panel (1)
- genetic (1)
- genetic causes of cancer (1)
- genetic counselling (1)
- genetic diagnosis (1)
- genetic diseases (1)
- genetic interaction networks (1)
- genetic loci (1)
- genetic model (1)
- genetic risk (1)
- genetic skeletal disorders (1)
- genetic susceptibility (1)
- genetic testing (1)
- genetic variants (1)
- genetische Beratung (1)
- genetische Erkrankungen (1)
- genome sequencing (1)
- genome-wide association study (GWAS) (1)
- genome-wide linkage analysis (1)
- genomic analysis (1)
- genomic instability (1)
- genomic libraries (1)
- genomics (1)
- genotyping arrays (1)
- geprägte Gene (1)
- germ-line mosaicism (1)
- germinal mosaicism (1)
- germline mosaicism (1)
- germline mutations (1)
- glaucoma (1)
- glycogenin 1 (1)
- gonads (1)
- granulomas (1)
- great dane (1)
- growth (1)
- growth failure (1)
- gynogenesis (1)
- haemophilia a (1)
- hand/foot malformation (1)
- haplogroups (1)
- haploinsufficiency (1)
- helicase BRIP1 (1)
- hematology (1)
- hemostasis and thrombosis (1)
- hereditary hearing loss (1)
- hereditary hemochromatosis (1)
- hereditary motor (1)
- hereditary motor and sensory neuropathy (1)
- heterogeneity (1)
- heteromorphic sex chromosomes (1)
- heterozygote (1)
- histological subtype (1)
- homoeologous chromosomes (1)
- hormone-related protein (1)
- host cells (1)
- human disease (1)
- human evolution (1)
- human medicine (1)
- humane Keimzellen (1)
- humans (1)
- hybridogenesis (1)
- hypermethylated DNA (1)
- hypermethylation (1)
- hypermutable (1)
- hämatopoetisches Mosaik (1)
- illumina (1)
- immune thrombocytopenia (1)
- imprinting control region (1)
- in situ hybridization (1)
- in vitro model (1)
- induced pluripotent stem cells (1)
- infinium HumanOmni1-Quad (1)
- inflammation (1)
- inflammatory diseases (1)
- inherited disorders (1)
- inherited myopathy (1)
- insulin treatment (1)
- integrierte Versorgung (1)
- intergenerational contraction (1)
- interolog (1)
- interstrand crosslink (1)
- intrachromosomal telomeric sequences (1)
- inversion (1)
- italian patients (1)
- juvenile and adult patients (1)
- karyotype evolution (1)
- kinase signaling (1)
- kongenitale Myopathie (1)
- limb development (1)
- limb-girdle dystrophie (1)
- limb-girdle muscular dystrophies (1)
- linkage analysis (1)
- linked myotubular myopathy (1)
- live-born (1)
- lymphoma (1)
- lyso‐Gb3 (1)
- macrophages (1)
- macula dystrophy (1)
- macular (1)
- maintenance (1)
- makula (1)
- male breast cancer (1)
- malformations (1)
- malignant hyperthermia (1)
- maligne Hyperthermie (1)
- mammalian male germline (1)
- mammographic density (1)
- medical genetics (1)
- meiosis (1)
- meiotic chromosomes (1)
- meiotic ‘superring’ (1)
- membrane curvature (1)
- membrane repair (1)
- mental retardation (1)
- metabolic disease (1)
- metabolism (1)
- methylation array (1)
- mice (1)
- microdeletion syndrome (1)
- microdissection (1)
- midbody (1)
- middle aged (1)
- mineraliztion (1)
- missense mutations (1)
- mitomycin c (1)
- mitotic chromosomes (1)
- mixed hearing loss (1)
- mixed mutation mechanisms (1)
- miyoshi myopathy (1)
- model (1)
- moderate-penetrance genes (1)
- molecular analysis (1)
- molecular cloning (1)
- monogeneic (1)
- monoubiquitination (1)
- monozygotic twins (1)
- morbidity (1)
- mortality (1)
- mouse (1)
- multi protein complex (1)
- multiple diseases (1)
- multiple myeloma (1)
- muscle disease (1)
- muscle strength (1)
- muscular dystrophy (1)
- muscular-dystrophy (1)
- mutation analysis (1)
- mutation mechanism (1)
- mutation rate (1)
- mutationrate (1)
- myotonic dystrophie (1)
- myotonic dytsrophy (1)
- natural variation (1)
- network analysis (1)
- network inference (1)
- networks (1)
- neurodegeneration (1)
- neurodevelopmental disorders / genetics (1)
- neuromuscular disease (1)
- neurotransmission (1)
- neutrophils (1)
- next-generation sequencing (1)
- next-generation-sequencing (1)
- nibrin (1)
- night blindness (1)
- nomenclature (1)
- non-mosaic (1)
- non-sense mediated mRNA decay (1)
- nonspecific alkaline-phosphae (1)
- oocytes (1)
- organ toxicity (1)
- overlapping syndrome (1)
- oxidative stress (1)
- p.R245H (1)
- p.S298P (1)
- p53-deficient mice overexpressing TGFalpha (1)
- painful (1)
- pancreatic carcinoma (1)
- panel sequencing (1)
- panic disorder (1)
- paternal age (1)
- paternal age effect (1)
- paternal introgression (1)
- pathogen-host interaction (PHI) (1)
- pathogenicity (1)
- pathway (1)
- patient (1)
- penetrance (1)
- phalloidin stain (1)
- phenotype (1)
- phenotypic heterogeneity (1)
- phenotypic spectrum (1)
- phosphoproteome (1)
- photoreceptor synapse (1)
- phylloquinone (1)
- plasma (1)
- platelet disorders (1)
- polymerase chain reaction (1)
- polymorphism (1)
- polyneuropathy (1)
- polyploidization (1)
- polyploidy (1)
- population (1)
- potential role (1)
- prednisone (1)
- premature aging (1)
- premutation (1)
- prenatal diagnosis (1)
- preterm labor (1)
- preterm prelabor rupture of the membranes (1)
- prevalence (1)
- promoter methylation (1)
- promotes (1)
- protein aggregation (1)
- protein interaction (1)
- protein interaction database (1)
- protein-protein interaction (1)
- proteins (1)
- proteomic approach (1)
- proteomic signature (1)
- protocadherin gamma cluster (1)
- proximal myotonic myopathy (1)
- pseudotetraploidisierung (1)
- pseudotetraploidization (1)
- psychische Probleme (1)
- psychosocial aspects (1)
- psychosoziale Aspekte (1)
- qPCR (1)
- quality control (1)
- quantitative Polymerasekettenreaktion (1)
- radial drusen (1)
- radiosensitivity (1)
- radiosensivitity (1)
- recessive inheritance (1)
- reciprocal translocation (1)
- recurrence (1)
- regulatory T cells (1)
- regulatory mutations (1)
- reproduction (1)
- requency (1)
- reversion (1)
- rhodamine–phalloidin stain (1)
- risk assesment (1)
- risk factors (1)
- robertsonian translocation (1)
- ryr 1 (1)
- sarcoglycanopathy (1)
- sarcotubular myopathy (1)
- secondary cancer (1)
- segmental progeria (1)
- selection (1)
- sensorineural (1)
- sensorineural hearing loss (1)
- sequence alignment (1)
- sequence assembly tools (1)
- sex chromosome evolution (1)
- sex linked pigmentation pattern (1)
- sex ratio (1)
- sexual antagonistic genes (1)
- short stature (1)
- skeletal muscle (1)
- skeletal myopathy (1)
- skewed (1)
- sky kinases (1)
- species-specific epigenetic marks (1)
- spektrale Karyotypenanalyse (1)
- spektrale karyotypisierung (1)
- spinal muscular atrophy (1)
- splicing (1)
- spondylodysplastic Ehlers-Danlos syndrome (1)
- stem cell transplantation (1)
- steroids (1)
- stress fibers (1)
- structural genome variations (1)
- submicroscopic chromosome rearrangement (1)
- subtypes (1)
- success (1)
- suppression (1)
- susceptibility (1)
- susceptibility alleles (1)
- susceptibility gene (1)
- synaptonemal complex (1)
- systemic sclerosis (1)
- targeted gene panel (1)
- teeth (1)
- telomere length (1)
- telomeres (1)
- temperature (1)
- testes (1)
- testosterone (1)
- therapy (1)
- throat (1)
- thrombozytopenia (1)
- tinnitus (1)
- tissue-specific enhancers (1)
- tooth development (1)
- transcription deficiency (1)
- transcriptional regulation (1)
- transcriptome (1)
- transgene TGFalpha-Mäuse (1)
- transgenic animals (1)
- transporter gene SLC2A3 (1)
- transposable elements (1)
- treatment (1)
- treatment guidelines (1)
- triple-negative breast cancer (1)
- triplosufficiency (1)
- trisomy 21 (1)
- trisomy 22 (1)
- tumor subtypes (1)
- tumor-suppressor (1)
- twin study (1)
- two-parameter flow cytometry (1)
- type II esophageal achalasia (1)
- ubiquitin (1)
- vacuolar myopathy (1)
- vascular malformation (1)
- vaskuläre Malformation (1)
- vectors (1)
- ventilation (1)
- vertebrate (1)
- werner syndrom (1)
- werner syndrome (1)
- whole genome amplification (1)
- whole genome sequencing (1)
- whole genome sequencing (WGS) (1)
- wuerzburg (1)
- zytogenetik (1)
- Änderung (1)
- Ätiologie (1)
- Ödem (1)
- α‐GalA 3D‐structure (1)
Institute
- Institut für Humangenetik (234)
- Theodor-Boveri-Institut für Biowissenschaften (48)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (6)
- Kinderklinik und Poliklinik (6)
- Fakultät für Biologie (5)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (5)
- Medizinische Klinik und Poliklinik I (5)
- Neurologische Klinik und Poliklinik (5)
- Lehrstuhl für Orthopädie (3)
- Institut für Anatomie und Zellbiologie (2)
Sonstige beteiligte Institutionen
- Comprehensive Hearing Center, Department of ORL, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Würzburg, Germany (1)
- DNA Analytics Core Facility, Biocenter, University of Würzburg, Würzburg, Germany (1)
- Department of Animal Ecology and Tropical Biology, University of Würzburg, Würzburg, Germany (1)
- Maastricht University, Maastricht, the Netherlands (1)
Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature
(2018)
Purpose
Short stature is a common condition of great concern to patients and their families. Mostly genetic in origin, the underlying cause often remains elusive due to clinical and genetic heterogeneity.
Methods
We systematically phenotyped 565 patients where common nongenetic causes of short stature were excluded, selected 200 representative patients for whole-exome sequencing, and analyzed the identified variants for pathogenicity and the affected genes regarding their functional relevance for growth.
Results
By standard targeted diagnostic and phenotype assessment, we identified a known disease cause in only 13.6% of the 565 patients. Whole-exome sequencing in 200 patients identified additional mutations in known short-stature genes in 16.5% of these patients who manifested only part of the symptomatology. In 15.5% of the 200 patients our findings were of significant clinical relevance. Heterozygous carriers of recessive skeletal dysplasia alleles represented 3.5% of the cases.
Conclusion
A combined approach of systematic phenotyping, targeted genetic testing, and whole-exome sequencing allows the identification of the underlying cause of short stature in at least 33% of cases, enabling physicians to improve diagnosis, treatment, and genetic counseling. Exome sequencing significantly increases the diagnostic yield and consequently care in patients with short stature.
BRCA1 is a tumor suppressor that regulates DNA repair by homologous recombination. Germline mutations in BRCA1 are associated with increased risk of breast and ovarian cancer and BRCA1 deficient tumors are exquisitely sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Therefore, uncovering additional components of this DNA repair pathway is of extreme importance for further understanding cancer development and therapeutic vulnerabilities. Here, we identify EDC4, a known component of processing-bodies and regulator of mRNA decapping, as a member of the BRCA1-BRIP1-TOPBP1 complex. EDC4 plays a key role in homologous recombination by stimulating end resection at double-strand breaks. EDC4 deficiency leads to genome instability and hypersensitivity to DNA interstrand cross-linking drugs and PARP inhibitors. Lack-of-function mutations in EDC4 were detected in BRCA1/2-mutation-negative breast cancer cases, suggesting a role in breast cancer susceptibility. Collectively, this study recognizes EDC4 with a dual role in decapping and DNA repair whose inactivation phenocopies BRCA1 deficiency.
Evolutionary conserved networks of human height identify multiple Mendelian causes of short stature
(2019)
Height is a heritable and highly heterogeneous trait. Short stature affects 3% of the population and in most cases is genetic in origin. After excluding known causes, 67% of affected individuals remain without diagnosis. To identify novel candidate genes for short stature, we performed exome sequencing in 254 unrelated families with short stature of unknown cause and identified variants in 63 candidate genes in 92 (36%) independent families. Based on systematic characterization of variants and functional analysis including expression in chondrocytes, we classified 13 genes as strong candidates. Whereas variants in at least two families were detected for all 13 candidates, two genes had variants in 6 (UBR4) and 8 (LAMA5) families, respectively. To facilitate their characterization, we established a clustered network of 1025 known growth and short stature genes, which yielded 29 significantly enriched clusters, including skeletal system development, appendage development, metabolic processes, and ciliopathy. Eleven of the candidate genes mapped to 21 of these clusters, including CPZ, EDEM3, FBRS, IFT81, KCND1, PLXNA3, RASA3, SLC7A8, UBR4, USP45, and ZFHX3. Fifty additional growth-related candidates we identified await confirmation in other affected families. Our study identifies Mendelian forms of growth retardation as an important component of idiopathic short stature.
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7−/− mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7−/− mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development.
Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype.
Laut des aktuellen Reports der Weltgesundheitsorganisation sind ca. 466 Millionen Menschen weltweit von einer Hörstörung (HS) betroffen. Durch die enorme Heterogenität und die klinische Variabilität, die diese Erkrankung ausmacht, und viele bisher nicht mit HS assoziierte Gene, bleibt ein großer Teil der erblich bedingten HS in vielen Familien unaufgeklärt. Die Entwicklung moderner Techniken, wie die Next-Generation Sequenzierung (NGS) und der Fortschritt bei der Untersuchung von Modellorganismen trugen jedoch in den letzten Jahren immens dazu bei, neue Gene zu identifizieren, die innerhalb des auditorischen Signalwegs oder damit assoziierten Strukturen beteiligt sind. Die vorliegende Arbeit umfasst Ergebnisse dreier Veröffentlichungen, in denen iranische und pakistanische Familien und eine deutsche Familie mit erblich bedingter HS untersucht und neue, krankheitsverursachende Varianten identifiziert und funktionell charakterisiert wurden. Im ersten Abschnitt konnten zwei neue rezessive Varianten im CDC14A-Gen als krankheitsverursachend identifiziert werden, die zu einem potentiellen Funktionsverlust des kodierten Proteins in einer iranischen und einer pakistanischen Familie führen. Mit Hilfe einer funktionellen Charakterisierung auf RNA-Ebene (Spleiß-Assay und RT-qPCR) konnte der Funktionsverlust beider Varianten bestätigt werden. Der zweite Abschnitt umfasst eine deutsche Familie mit sieben von einer HS betroffenen Familienmitgliedern, in der eine heterozygote missense Variante in MYO3A identifiziert wurde. In der vorliegenden Arbeit konnte somit die erste autosomal dominante Variante in einer europäischen Familie mit einer bilingualen, sensorineuralen Hochtonschwerhörigkeit beschrieben werden und der dominante Charakter von MYO3A bestätigt werden. Im dritten Abschnitt konnten die krankheitsverursachenden Varianten in 13 Familien aus einer Kohorte mit 21 pakistanischen Familien mit einer syndromalen und nicht-syndromalen HS ausfindig gemacht werden. Hierbei wurden sowohl bekannte, als auch bisher nicht beschriebene Varianten detektiert. Die Aufklärungsrate innerhalb dieser Kohorte betrug 61,9% und es konnte somit das Spektrum syndromaler und nicht-syndromaler HS erweitert werden. Der letzte Abschnitt dieser Arbeit beschreibt eine iranische Familie mit einer milden HS und milden Intelligenzminderung, in der eine homozygote missense Variante im Kandidatengen DBN1 ausfindig gemacht wurde. Um die Funktion und die Auswirkungen eines potentiellen Verlusts des codierten Proteins Drebrin zu untersuchen, wurden immunhistochemische Färbungen und auditorische Messungen an Dbn1 Knockout (KO)-Mäusen durchgeführt. Hierbei konnte eine Expression innerhalb der Nervenfasern, die innere Haarzellen innervieren, nachgewiesen werden. Eine leicht verlängerte Latenz für die ABR-Welle IV in KO-Mäusen im Vergleich zum Wildtyp ergab den Hinweis auf einen Defekt innerhalb des zentralen auditorischen Signalwegs, der möglicherweise mit einer Sprachverarbeitungsstörung im Menschen korreliert.
Western societies are steadily becoming older undergoing a clear trend of delayed parenthood. Children of older fathers have an undeniably higher risk for certain neurodevelopmental disorders and other medical conditions. Changes in the epigenetic landscape and especially in DNA methylation patterns are likely to account for a portion of this inherited disease susceptibility. DNA methylation changes during the ageing process are a well-known epigenetic feature. These so-called age-DMRs exist in developmentally important genes in the methylome of several mammalian species. However, there is only a minor overlap between the age-DMR datasets of different studies. We therefore replicated age-DMRs (which were obtained from a genome wide technique) by applying a different technical approach in a larger sample number. Here, this study confirmed 10 age-DMRs in the human and 4 in the bovine sperm epigenome from a preliminary candidate list based on RRBS. For this purpose, we used bisulphite Pyrosequencing in 94 human and 36 bovine sperm samples. These Pyrosequencing results confirm RRBS as an effective and reliable method to screen for age-DMRs in the vertebrate genome. To decipher whether paternal age effects are an evolutionary conserved feature of mammalian development, we compared methylation patterns between human and bovine sperm in orthologous regulatory regions. We discovered that the level of methylation and the age effect are both species-specific and speculate that these methylation marks reflect the lineage-specific development of each species to hit evolutionary requirements and adaptation processes. Different methylation levels between species in developmentally important genes also imply a differing mutational burden, representing a potential driver for point mutations and consequently deviations in the underlying DNA sequence of different species. Using the example of different haplotypes, this study showed the great effect of single base variations on the methylation of adjacent CpGs. Nonetheless, this study could not provide further evidence or a mechanism for the transfer of epigenetic marks to future generations. Therefore, further research in tissues from the progeny of old and young fathers is required to determine if the observed methylation changes are transmitted to the next generation and if they are associated with altered transcriptional activity of the respective genes. This could provide a direct link between the methylome of sperm from elderly fathers and the development potential of the next generation.
The research that is compiled in this thesis can be divided in two parts. The first part, consisting of four chapters, is centered around the role of epigenetic dysregulation in the etiopathophysiology of sporadic alzheimer's disease (sAD). In addition to providing insights into the most recent developments in neuroepigenomic studies of this disease, the first part of the thesis also touches upon remaining challenges, and provides a future outlook on possible developments in the field. The second part, which includes three more chapters, is focused on the application of induced pluripotent stem cell (iPSC)-based disease models for the study of AD, including but not limited to mechanistic studies on epigenetic dysregulation using this platform. Aside from outlining the research that has been conducted using iPSC-based models for sAD to date, the second part of the thesis also provides insights into the acquisition of disease-relevant neural cultures based on directed differentiation of iPSCs, and furthermore includes an experimental approach for the establishment of such a model system.