TY  - JOUR
A1  - Maierhofer, Anna
A1  - Flunkert, Julia
A1  - Oshima, Junko
A1  - Martin, George M.
A1  - Poot, Martin
A1  - Nanda, Indrajit
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Haaf, Thomas
T1  - Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes
JF  - Aging Cell
N2  - Werner Syndrome (WS) is an adult‐onset segmental progeroid syndrome. Bisulfite pyrosequencing of repetitive DNA families revealed comparable blood DNA methylation levels between classical (18 WRN‐mutant) or atypical WS (3 LMNA‐mutant and 3 POLD1‐mutant) patients and age‐ and sex‐matched controls. WS was not associated with either age‐related accelerated global losses of ALU, LINE1, and α‐satellite DNA methylations or gains of rDNA methylation. Single CpG methylation was analyzed with Infinium MethylationEPIC arrays. In a correspondence analysis, atypical WS samples clustered together with the controls and were clearly separated from classical WS, consistent with distinct epigenetic pathologies. In classical WS, we identified 659 differentially methylated regions (DMRs) comprising 3,656 CpG sites and 613 RefSeq genes. The top DMR was located in the HOXA4 promoter. Additional DMR genes included LMNA, POLD1, and 132 genes which have been reported to be differentially expressed in WRN‐mutant/depleted cells. DMRs were enriched in genes with molecular functions linked to transcription factor activity and sequence‐specific DNA binding to promoters transcribed by RNA polymerase II. We propose that transcriptional misregulation of downstream genes by the absence of WRN protein contributes to the variable premature aging phenotypes of WS. There were no CpG sites showing significant differences in DNA methylation changes with age between WS patients and controls. Genes with both WS‐ and age‐related methylation changes exhibited a constant offset of methylation between WRN‐mutant patients and controls across the entire analyzed age range. WS‐specific epigenetic signatures occur early in life and do not simply reflect an acceleration of normal epigenetic aging processes.
KW  - (classical and atypical) Werner syndrome
KW  - bisulfite pyrosequencing
KW  - methylation array
KW  - premature aging
KW  - segmental progeria
KW  - transcription deficiency
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202733
VL  - 18
ER  - 
TY  - JOUR
A1  - El Hajj, Nady
A1  - Dittrich, Marcus
A1  - Böck, Julia
A1  - Kraus, Theo F. J.
A1  - Nanda, Indrajit
A1  - Müller, Tobias
A1  - Seidmann, Larissa
A1  - Tralau, Tim
A1  - Galetzka, Danuta
A1  - Schneider, Eberhard
A1  - Haaf, Thomas
T1  - Epigenetic dysregulation in the developing Down syndrome cortex
JF  - Epigenetics
N2  - Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3-11times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methylation in neuroprogenitors, which then persists in the fetal DS brain where DNMT3A and DNMT3B become downregulated. The vast majority of differentially methylated promoters and genes was hypermethylated in DS and located outside chromosome 21, including the protocadherin gamma (PCDHG) cluster on chromosome 5q31, which is crucial for neural circuit formation in the developing brain. Bisulfite pyrosequencing and targeted RNA sequencing showed that several genes of PCDHG subfamilies A and B are hypermethylated and transcriptionally downregulated in fetal DS cortex. Decreased PCDHG expression is expected to reduce dendrite arborization and growth in cortical neurons. Since constitutive hypermethylation of PCDHG and other genes affects multiple tissues, including blood, it may provide useful biomarkers for DS brain development and pharmacologic targets for therapeutic interventions.
KW  - trisomy 21
KW  - DNA methylation
KW  - Down syndrome
KW  - fetal brain development
KW  - frontal cortex
KW  - protocadherin gamma cluster
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191239
VL  - 11
IS  - 8
ER  - 
TY  - JOUR
A1  - Rodríguez-Mari, Adriana
A1  - Wilson, Catherine
A1  - Titus, Tom A.
A1  - Canestro, Cristian
A1  - BreMiller, Ruth A.
A1  - Yan, Yi-Lin
A1  - Nanda, Indrajit
A1  - Johnston, Adam
A1  - Kanki, John P.
A1  - Gray, Erin M.
A1  - He, Xinjun
A1  - Spitsbergen, Jan
A1  - Schindler, Detlev
A1  - Postlethwait, John H.
T1  - Roles of brca2 (fancd1) in Oocyte Nuclear Architecture, Gametogenesis, Gonad Tumors, and Genome Stability in Zebrafish
JF  - PLoS Genetics
N2  - Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: (25.0 +/- 2.8) years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V(gray)) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6 +/- 0.7) mm considering the deepest 5% of light. Of the detected photon packages scalp and bone absorbed (96.4 +/- 9: 7)% and V(gray) absorbed (3.1 +/- 1.8)% of the energy. The mean V(gray) volume (1.1 +/- 0.4)cm(3) was negatively correlated (r = - .76) with the SCD and frontal sinus volume (r = - .57) and was reduced by 41.5% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r = .46) and the traversed frontal sinus volume (r = .43). Sulcal morphology had no significant impact on V(gray). Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance.
KW  - oocytes
KW  - zebrafish
KW  - genetic causes of cancer
KW  - testes
KW  - apoptosis
KW  - gonads
KW  - sperm
KW  - embryos
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142285
VL  - 7
IS  - 3
ER  - 
TY  - JOUR
A1  - Schneider, Eberhard
A1  - Dittrich, Marcus
A1  - Böck, Julia
A1  - Nanda, Indrajit
A1  - Müller, Tobias
A1  - Seidmann, Larissa
A1  - Tralau, Tim
A1  - Galetzka, Danuta
A1  - El Hajj, Nady
A1  - Haaf, Thomas
T1  - CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development
JF  - Gene
N2  - Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767 m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny.
KW  - Autism spectrum disorders
KW  - DNA methylation
KW  - Genome
KW  - Autism
KW  - Frontal cortex
KW  - Human prefrontal cortex
KW  - Gene-expression
KW  - Schizophrenia
KW  - Patterns
KW  - Transcription
KW  - Epigenetics
KW  - Environment
KW  - Fetal brain development
KW  - DNA methylation dynamics
KW  - Methylome
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186936
VL  - 592
IS  - 1
ER  - 
TY  - JOUR
A1  - Schlupp, Ingo
A1  - Parzefall, Jakob
A1  - Epplen, Jörg T.
A1  - Nanda, Indrajit
A1  - Schmid, Michael
A1  - Schartl, Manfred
T1  - Pseudomale behaviour and spontaneous masculinization in the all-female teleost Poecilia formosa (Teleostei: Poeciliidae)
N2  - Pseudosexual behaviour is a rare phenomenon associated with unisexuality in vertebrates. In the gynogenetic, all-female teleost Poecilia formosa, rare individuals occur that resemble males of closely related gonochoristic species both in behaviour and external morphology. These masculinized gynogens and normal gynogens are members of the same clone, as demonstrated by DNA-fingerprinting. The behaviour of these masculinized gynogens is described and compared to the behaviour of the gonochoristic species Poecilia mexicana, P. latipinna and their hybrid as weil as androgen-treated individuals of P. formosa. No statistically significant difTerences were found between masculinized gynogens and hormonetreated individuals nor between the gonochoristic P. mexicana and P. latipinna males. Differences exist between gonochoristic and unisexual species. Passihle causes and effects of masculinized gynogens are discussed.
KW  - Physiologische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61688
ER  - 
TY  - JOUR
A1  - Schartl, Manfred
A1  - Erbelding-Denk, Claudia
A1  - Holter, Sabine
A1  - Nanda, Indrajit
A1  - Schmid, Michael
A1  - Schroder, Johannes H.
A1  - Epplen, Jörg T.
T1  - Reproductive failure of dominant males in the poeciliid fish Limia perugiae determined by DNA fingerprinting
N2  - Hierarchical structures among male indlviduals in a population are frequently reflected ln differences in aggressive and reproductive behavior and access to the females. In general, sodal dominance requires the Investments, which in turn then may have to be compensated for by high reproductive success. However, this hypothesls has so far only been sufficiently tested in small mating groups (one or two males with one or two females) due to the difficulties of determining paternity by conventional methods. DNA fingerprinting overcomes these problems by offering the possibility to determine genetic relationships and mating patterns within larger groups [Borke, T. (1989) Trends Ecol. Evol. 4, 139-144]. We show here that in the poecUiid fish Limia perugitu, in small matlng groups the dominant male has 8 mating success of 100%, whereas ln larger groups lts contribution to the offspring unexpectedly drops to zero.
KW  - Physiologische Chemie
KW  - reproductive success
KW  - sexual selection
KW  - size polymorpbism
KW  - sodal domlnance
KW  - simple repetitive sequences
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61643
ER  - 
TY  - JOUR
A1  - Nanda, Indrajit
A1  - Schartl, Manfred
A1  - Epplen, Jörg T.
A1  - Feichtinger, Wolfgang
A1  - Schmid, Michael
T1  - Primitive sex chromosomes in poeciliid fishes harbor simple repetitive DNA sequences
N2  - The demonstration ofthe chromosomal mode ofsex determinationvia genetic experiments as well as the absence of heteromorphic sex chromosomes affirm poeciliid fishes as a unique group among vertebrates that are endowed with the mostprimitive form of sex chromosornes. In many different taxa the evolutionary process involved in the differentiation ofadvanced sex chromosomes is outlined through sex specifically organized repetitive sequences. In this investigation hydridization of synthetic probes specific to genomic simple repeat motifs uncovers a sex-specific hybridization pattern in certain viviparaus fishes ofthe family Poeciliidae. The hybridization pattern together with specific staining ofthe constitutive heterochromatin by C-banding reveals heterogamety in males (Poecilia reticulata) as weil as in females (P. sphenops). In P. velifera, however, C-banding alone fails to unravel the heterogametic status. The female specific W-chromosome can be detected by simple repetitive sequence probes. Therefore, the principal significance of heterochromatization as a means of generating differentiated sex chromosomes is evident.
KW  - Physiologische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61659
ER  - 
TY  - JOUR
A1  - Erbelding-Denk, Claudia
A1  - Schroder, Johannes H.
A1  - Schartl, Manfred
A1  - Nanda, Indrajit
A1  - Schmid, Michael
A1  - Epplen, Jörg T.
T1  - Male polymorphism in Limia perugiae (Pisces: Poeciliidae)
N2  - The male-polymorphic poeciliid fish, Limia perugiae, a small teleostean endemic to the southeast of the Caribbean island Hispafiola, consists of three male size morphs with uniform females. Large males differentiate at a size va:rying between 25 and 38 mm; intermediate males, between 21 and 25 mm. Under competition, !arge males exhibit an elaborate courtship display, whereas small males show only a sneak-chase behavior. Intermediate males adapt their tactics to the respective competitors. However, all malemorphs can switch from courtship display to sneak-chase behavior. In large mating groups with four males of different size and five or six virgin females, large dominant a-males as weil as small subordinate \(\delta\)-males did not produce any offspring. Unexpectedly, all progeny were sired exclusively by the intemediate subordinate ß- and \(\gamma\)-males. Breeding experiments with the three male morphs can best be explained by a model of Y -linked genes for small and !arge size which are both suspended by the activity of an autosomal recessive repressor responsible for the development of intermediate males. The dominant allele of the recessive repressor, in either its homoorits heterozygous state, activates the Y-chromosomal genes for !arge or small size, respectively. Accordingly, intermediate males may produce male offspring of all size classes, depending on the presence of either the Y-linked gene or the autosomal repressor.
KW  - Physiologische Chemie
KW  - Poeciliid fish
KW  - male size polymorphism
KW  - reproductive success
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61573
ER  - 
TY  - JOUR
A1  - Nanda, Indrajit
A1  - Schartl, Manfred
A1  - Feichtinger, Wolfgang
A1  - Epplen, Jörg T.
A1  - Schmid, Michael
T1  - Early stages of sex chromosome differentiation in fish as analysed by simple repetitive DNA sequences
N2  - Animal sex chromosome evolution has started on different occasions with a homologous pair of autosomes leading to morphologically differentiated gonosomes. In contrast to other vertebrate classes, among fishes cytologically dernonstrahle sex chromosomes are rare. In reptiles, certain motifs of simple tandemly repeated DNA sequences like (gata)\(_n\)/(gaca)\(_m\) are associated with the constitutive heterochromatin of sex chromosomes. In this study a panel of simple repetitive sequence probes was hybridized to restriction enzyme digested genomic DNA of poeciliid fishes. Apparent male heterogamety previously established by genetic experiments in Poecilia reticulata (guppy) was correlated with male-specific hybridization using the (GACA)\(_4\) probe. The (GATA)\(_4\) oligonucleotide identifies certain male guppies by a Y chromosomal polymorphism in the outbred population. In cantrast none of the genetically defined heterogametic situations in Xiphophorus could be verified consistently using the collection of simple repetitive sequence probes. Only individuals from particular populations produced sex-specific patterns of hybridization with (GATA)\(_4\). Additional poeciliid species (P. sphenops, P. velifera) harbour different sex-specifically organized simple repeat motifs. The observed sex-specific hybridization patterns were substantiated by banding analyses of the karyotypes and by in situ hybridization using the (GACA)\(_4\) probe.
KW  - Physiologische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61715
ER  - 
TY  - JOUR
A1  - Schartl, Manfred
A1  - Schlupp, Ingo
A1  - Schartl, Angelika
A1  - Meyer, Manfred K.
A1  - Nanda, Indrajit
A1  - Schmid, Michael
A1  - Epplen, Jörg T.
A1  - Parzefall, Jakob
T1  - On the stability of dispensable constituents of the eukaryotic genome: Stability of coding sequences versus truly hypervariable sequences in a clonal vertebrate, the amazon molly, Poecilia formosa
N2  - In dooal unisexual vertebrales, the genes specifying the males become dispensable. To study tbe rate of such geoes the gynogeoetic all-female fisb Poecilillfonnolll was treated with androgens. Phenotypic males were obtained that exbibited the complete set of male cbaracteristics of dosely related gooocboristic species, induding body proportions, pigmentation, the extremely complex insemination apparatus of poecilüd fish, sexual bebavior, and spermatogeoesls. Tbe apparent stabllity of such genic structures, induding those involved in androgen regulation, is contrasted by high instability of noncoding sequeaces. Frequent mutations, thelr donal transmission, and at least two truly hypervariable Iod leading to individual difl'ereaces between these othenrise donal organisms were detected by DNA fingerprinting. These observations substantiate the concept that also in "ameiotic" vertebrates certain compartments of the genome are more prooe to mutatiooal alterations than others.
KW  - Physiologische Chemie
KW  - DNA fingerprinting
KW  - androgen-induced masculinization
KW  - gynogeaesls
KW  - simple repeat sequences
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61731
ER  -