TY  - JOUR
AB  - During the birch pollen season an enhanced incidence of virus infections is noticed, raising the question whether pollen can affect anti-viral responses independent of allergic reactions. Indeed, we previously showed that birch pollen-treatment of monocyte-derived dendritic cells (moDC) enhances human cytomegalovirus (HCMV) infection. Here we addressed how in moDC the relatively weak pollen response can affect the comparably strong response to HCMV. To this end, moDC were stimulated with aqueous birch pollen extract (APE), HCMV, and APE + HCMV, and transcriptomic signatures were determined after 6 and 24 h of incubation. Infection was monitored upon exposure of moDC to GFP expressing HCMV by flow cytometric analysis of GFP expressing cells. Principle component analysis of RNA sequencing data revealed close clustering of mock and APE treated moDC, whereas HCMV as well as APE + HCMV treated moDC clustered separately after 6 and 24 h of incubation, respectively. Communally induced genes were detected in APE, HCMV and APE + HCMV treated moDC. In APE + HCMV treated moDC, the comparably weak APE induced signatures were maintained after HCMV exposure. In particular, NF-κB/RELA and PI3K/AKT/MAPK signaling were altered upon APE + HCMV exposure. Earlier, we discovered that NF-κB inhibition alleviated APE induced enhancement of HCMV infection. Here we additionally found that impairment of PI3K signaling reduced HCMV infection in HCMV and APE + HCMV treated moDC. APE treated moDC that were exposed to HCMV show a unique host gene signature, which to a large extent is regulated by NF-κB activation and PI3K/AKT/MAPK signaling.
AU  - Fneish, Z.*
AU  - Becker, J.*
AU  - Mulenge, F.*
AU  - Fneish, F.*
AU  - Costa, B.*
AU  - Traidl-Hoffmann, C.
AU  - Gilles, S.
AU  - Kalinke, U.*
C1  - 70820
C2  - 55942
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Birch pollen-induced signatures in dendritic cells are maintained upon additional cytomegalovirus exposure.
JO  - Gene
VL  - 927
PB  - Elsevier
PY  - 2024
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Background: Congenital heart defects (CHD) are the most common birth defect and disease-causing variant in TAB2 have found to be associated with isolated CHD. Recently, it became evident that pathogenic, mostly loss-of-function variants in TAB2 can also cause syndromic CHD that includes connective tissue anomalies. The number of published cases is limited posing a challenge for counseling affected patients and their relatives. Methods: Cases in whom whole exome sequencing was executed at our institute between January 2015 and June 2021 were screened for disease-causing variants in TAB2. Additionally, a PubMed-based review of the literature was performed in December 2021 in order to give an updated clinical overview of the TAB2-associated phenotypic spectrum, including our cases. Results: We identified three cases with syndromic CHD caused by different heterozygous loss-of-function variants in TAB2. In one of these cases, the variant was inherited by a healthy father. A comparison with published cases highlights that most patients were affected by structural and/or arrhythmic heart disease (about 90%) while about two third of all cases had syndromic comorbidity especially connective tissue defects and dysmorphic abnormalities. Conclusion: Our findings indicate a variable expressivity as well as reduced penetrance of TAB2-associated CHD. Disease-causing variants in TAB2 should be considered in cases with isolated CHD but also in syndromic CHD with connective tissue abnormalities. However, prediction of the patients’ clinical outcome solely based on the variant in TAB2 is still extremely challenging.
AU  - Westphal, D.S.*
AU  - Mastantuono, E.*
AU  - Seidel, H.*
AU  - Riedhammer, K.M.*
AU  - Hahn, A.*
AU  - Vill, K.*
AU  - Wagner, M.
C1  - 63974
C2  - 52036
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - There is more to it than just congenital heart defects – The phenotypic spectrum of TAB2-related syndrome.
JO  - Gene
VL  - 814
PB  - Elsevier
PY  - 2022
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Correct diagnosis of children presenting with developmental delay and intellectual disability remains challenging due to the complex and heterogeneous etiology. High throughput sequencing technologies like exome sequencing have become more commonly available and are significantly improving genetic testing. We present two siblings – a 14-year old male and an 8-year old female patient – with a similar clinical phenotype that was characterized by combined developmental delay primarily affecting speech, mild to moderate intellectual disability, behavioral abnormalities, and autism spectrum disorder, but with no congenital anomalies. The sister showed additional muscular hypotonia and more pronounced dysmorphic features compared to her brother. Both parents had psychiatric disorders and mild to moderate intellectual disability. A common genetic etiology in the siblings was suspected. Metabolic, psychological and neuroradiological examinations were complemented by basic genetic testing including chromosome analysis and array comparative genomics hybridization analysis (CGH), followed by exome sequencing and combined data analysis of the family. Exome sequencing identified two different underlying genetic conditions: in the sister, a maternally inherited pathogenic variant c.1661C > T, p.Pro554Leu in SLC6A8 (NM_005629.4) was identified causing cerebral creatine deficiency syndrome 1 (MIM #300352) which was confirmed by MR spectroscopy and treated accordingly. In the brother, a paternally inherited 16p13.11 duplication was identified by exome sequencing and considered to be likely associated with his and possibly his father's phenotype. The 16p13.11 duplication had been previously identified in an array CGH but had not been prioritized due to the lack of segregation in the siblings. In conclusion, we report a case of intra-familial locus heterogeneity of developmental delay in two siblings. We advocate for the need of unbiased and comprehensive genetic testing to provide accurate diagnosis despite locus heterogeneity.
AU  - Brugger, M.*
AU  - Brunet, T.*
AU  - Wagner, M.
AU  - Orec, L.E.*
AU  - Schwaibold, E.M.C.*
AU  - Boy, N.*
C1  - 60493
C2  - 49480
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Locus heterogeneity in two siblings presenting with developmental delay, intellectual disability and autism spectrum disorder.
JO  - Gene
VL  - 768
PB  - Elsevier
PY  - 2021
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Background: Mutations in the ATP1A3 gene are known to be the cause of three distinct neurological syndromes including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP) and cerebellar ataxia, arefexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS). Recent studies have suggested the broader diversity of ATP1A3-related disorders. This study aimed to investigate the clinical spectrum in patients carrying causative mutations within the ATP1A3 gene.Method: The medical histories of nine unrelated patients with diverse phenotypes harboring variants in ATP1A3 were retrospectively analyzed after they were referred to a tertiary epilepsy center in one of the two different health care systems (Germany or Thailand). Clinical features, neurophysiological data, imaging results, genetic characteristics and treatments were reviewed.Results: Three patients harbor novel mutations in the ATP1A3 gene. Atypical clinical features and imaging findings were observed in two cases, one with hemiplegia-hemiconvulsion-epilepsy syndrome, and the other with neurodegeneration with brain iron accumulation. All nine patients presented with intellectual impairment. Alternating hemiplegia of childhood (AHC) was the most common phenotype (67%). Flunarizine and topiramate led to symptom reduction in 83% and 25% of AHC cases administered, respectively.Conclusion: The present case series expands the clinical and genetic spectrum of ATPIA3-related disorders.
AU  - Boonsimma, P.*
AU  - Gasser, M.M.*
AU  - Netbaramee, W.*
AU  - Wechapinan, T.*
AU  - Srichomthong, C.*
AU  - Ittiwut, C.*
AU  - Wagner, M.
AU  - Krenn, M.*
AU  - Zimprich, F.*
AU  - Abicht, A.*
AU  - Biskup, S.*
AU  - Roser, T.*
AU  - Borggraefe, I.*
AU  - Suphapeetiporn, K.*
AU  - Shotelersuk, V.*
C1  - 59351
C2  - 48785
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Mutational and phenotypic expansion of ATP1A3-related disorders: Report of nine cases.
JO  - Gene
VL  - 749
PB  - Elsevier
PY  - 2020
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Homozygous loss-of-function variants in MYO18B have been associated with congenital myopathy, facial dysmorphism and Klippel-Feil anomaly. So far, only four patients have been reported. Comprehensive description of new cases that help to highlight recurrent features and to further delineate the phenotypic spectrum are still missing. We present the fifth case of MYO18B-associated disease in a newborn male patient. Trio exome sequencing identified the previously unreported homozygous nonsense variant c.6433C > T, p.(Arg2145*) in MYO18B (NM_032608.5). While most phenotypic features of our patient align with previously reported cases, we describe the prenatal features for the first time. Taking the phenotypic description of our patient into account, we propose that the core phenotype comprises a severe congenital myopathy with feeding difficulties in infancy and characteristic dysmorphic features.
AU  - Brunet, T.*
AU  - Westphal, D.S.*
AU  - Weber, S.
AU  - Juenger, H.*
AU  - Vlaho, S.*
AU  - Hoefele, J.*
AU  - Meitinger, T.*
AU  - Rieger-Fackeldey, E.*
AU  - Wagner, M.
C1  - 58709
C2  - 48605
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - A novel pathogenic variant in MYO18B associating early-onset muscular hypotonia, and characteristic dysmorphic features, delineation of the phenotypic spectrum of MYO18B-related conditions.
JO  - Gene
VL  - 742
PB  - Elsevier
PY  - 2020
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Lymphedema are characterized by interstitial edema leading to swelling of extremities. They can be divided into primary and secondary lymphedema. Developmental abnormalities of the lymphatic system are responsible for the primary form of lymphedema. The secondary form of lymphedema is caused by damage of the lymphatic system due to external factors.Lymphedema can rarely be observed in patients with tuberous sclerosis complex (TSC), which is a neurocutaneous syndrome caused by pathogenic variants in the genes TSC1 or TSC2. Patients with TSC usually present with neurological manifestations and the development of multiple benign tumors of ectodermal origin. Typical onset for several symptoms is during the first year of life and in some cases lesions can be detected prenatally. Epilepsy is one of the most common manifestations, affecting up to 90% of TSC patients, and is associated with developmental delay. Early pharmacotherapy improves long term patient outcome.Trio exome sequencing was performed in a 3 weeks old girl with congenital lymphedema of the right lower extremity. Using a filter for de novo variants, the heterozygous missense variant c.2524C > T, p.(Gln842Ter) in TSC1 (NM_000368.4) could be identified. After the first onset of infantile spams at age 7 months treatment with vigabatrin was started immediately.We propose to include TSC1 and TSC2 analysis in the diagnostic work-up of patients with (isolated) congenital lymphedema as early diagnosis facilitates consequent treatment strategies potentially improving the prognosis of TSC patients.
AU  - Klinner, J.*
AU  - Krüger, M.*
AU  - Brunet, T.*
AU  - Makowski, C.*
AU  - Riedhammer, K.M.*
AU  - Mollweide, A.*
AU  - Wagner, M.
AU  - Hoefele, J.*
C1  - 59306
C2  - 48776
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
TI  - Congenital lymphedema as a rare and first symptom of tuberous sclerosis complex.
JO  - Gene
VL  - 753
PB  - Elsevier
PY  - 2020
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Patients with co-occurrence of two independent pathologies pose a challenge for clinicians as the phenotype often presents as an unclear syndrome. In these cases, exome sequencing serves as a powerful instrument to determine the underlying genetic causes. Here, we present the case of a 4-year old boy with proteinuria, microhematuria, hypercalciuria, nephrocalcinosis, livedo-like rash, recurrent abdominal pain, anemia and continuously elevated CRP. Single exome sequencing revealed the pathogenic nonsense mutation p.(Arg98*) in the CLCN5 gene causing the X-linked inherited, renal tubular disorder Dent's disease. Furthermore, the two pathogenic and compound heterozygous missense variants p.(Gly47Ala) and p.(Pro251Leu) in the CECR1 gene could be identified. Mutations in the CECR1 gene are associated with a hereditary form of polyarteritis nodosa, called ADA2-deficiency. Both parents were carriers of a single heterozygous variant in CECR1 and the mother was carrier of the CLCN5 variant. This case evidently demonstrates the advantage of whole exome sequencing compared to single gene testing as the pathology in the CECR1 gene might have only been diagnosed after the occurrence of signs of systemic vasculitis like strokes or hemorrhages. Therefore, treatment and prevention can now start early to improve the outcome of these patients.
AU  - Günthner, R.*
AU  - Wagner, M.
AU  - Thurm, T.*
AU  - Ponsel, S.*
AU  - Höfele, J.*
AU  - Lange-Sperandio, B.*
C1  - 52867
C2  - 44507
CY  - Amsterdam
SP  - 23-26
TI  - Identification of co-occurrence in a patient with Dent's disease and ADA2-deficiency by exome sequencing.
JO  - Gene
VL  - 649
PB  - Elsevier Science Bv
PY  - 2018
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Patients with Silver-Russell syndrome (SRS), a syndromic growth retardation syndrome, usually harbor an epimutation at chromosome 11p15 or a maternal uniparental disomy of chromosome 7. However, to date the genetic cause remains unknown in around 40% of SRS cases, suggesting genetic heterogeneity and involvement of other genes.We present a 4-year-old female patient with the clinical diagnosis of SRS and negative results in common genetic SRS diagnostics. Whole exome sequencing identified a de novo heterozygous 7.3 kb deletion on chromosome 12q14.3 including exon 1 and 2 of HMGA2.HMGA2 encodes an architectural transcription factor and has already been linked to body size variations in various genome-wide association studies and mouse models. Reviewing the literature, we found additional four patients with a phenotype of SRS harboring point mutations or structural variants involving HMGA2. We conclude that genetic testing of HMGA2 should be considered in routine diagnostics in patients with the suspicion of SRS.
AU  - Leszinski, G.S.*
AU  - Warncke, K.*
AU  - Hoefele, J.*
AU  - Wagner, M.
C1  - 53407
C2  - 44849
CY  - Po Box 211, 1000 Ae Amsterdam, Netherlands
SP  - 110-114
TI  - A case report and review of the literature indicate that HMGA2 should be added as a disease gene for Silver-Russell syndrome.
JO  - Gene
VL  - 663
PB  - Elsevier Science Bv
PY  - 2018
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Microdeletion 1q44 on the long arm of chromosome 1 leads to a phenotype that includes microcephaly, seizure, agenesis or hypogenesis of the corpus callosum, polydactyly, congenital heart defects and severe developmental delay along with characteristic facial dysmorphic signs. Until today, the distinct genetic causes for the different symptoms remain unclear. We here report a 1.2Mb de novo microdeletion 1q44 identified by performing a SNP array analysis. The female patient presented with microcephaly, seizure, hypogenesis of corpus callosum, postaxial hexadactyly, an atrial septal defect, a ventricular septal defect, hypertelorism, a long and smooth philtrum, thin vermilion borders, and micrognathia, all common features of microdeletion 1q44. An additionally performed chromosome analysis excluded any chromosomal rearrangements. The deleted region included the genes ZBTB18 as well as HNRNPU amongst others. Both are possibly candidate genes for the dysgenesis of the corpus callosum. AKT3, another candidate gene, was not affected by the deletion in this patient. Thus, the genetic findings in this case report spotlight ZBTB18 and HNRNPU in the genesis of the typical microdeletion 1q44 symptoms, especially concerning the dysgenesis of the corpus callosum, and therefore could help to unveil more of the genetic background of this syndrome.
AU  - Westphal, D.S.
AU  - Andres, S.*
AU  - Beitzel, K.I.*
AU  - Makowski, C.*
AU  - Meitinger, T.
AU  - Hoefele, J.*
C1  - 50790
C2  - 42861
CY  - Amsterdam
SP  - 41-44
TI  - Identification of a de novo microdeletion 1q44 in a patient with hypogenesis of the corpus callosum, seizures and microcephaly - A case report.
JO  - Gene
VL  - 616
PB  - Elsevier Science Bv
PY  - 2017
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Using a gene trap approach in ES cells, the novel mouse gene Trm1-like with substantial sequence homology to human C1orf25 mRNA (GenBank accession no. AF288399) was identified. Murine Trm1-like encodes a putative protein with limited similarity to N2,N2-dimethylguanosine tRNA methyltransferase (Trm1) from other organisms, however its function is not known. The potential role of Trm1-like was investigated in a mouse mutant lacking intact Trm1-like transcripts due to integration of the gene trap vector in the first intron. Trm1-like deficient mice are viable and show no apparent anatomical defects. Behavioural tests, however, revealed significantly altered motor coordination and aberrant exploratory behaviour. LacZ activity of the trapped mouse Trm1-like gene reflects expression in various neuronal structures during embryonic development, including spinal ganglia, trigeminal nerve and ganglion, olfactory and nasopharyngeal epithelium, and nuclei of the metencephalon, thalamus and medulla oblongata. The gene is also expressed in lung, oesophagus, epiglottis, ependyma, vertebral column, spinal cord, and brown adipose tissue. Trm1-like expression persists in the adult brain with dynamically changing patterns in cortex and cerebellum. Although Trm1-like is not essential for embryonic mouse development, it may have a role in modulating postnatal neuronal functions.
AU  - Vauti, F.*
AU  - Goller, T.*
AU  - Beine, R.*
AU  - Becker, L.*
AU  - Klopstock, T.*
AU  - Hölter, S.M.
AU  - Wurst, W.
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Hrabě de Angelis, M.
AU  - Arnold, H.-H.*
C1  - 2587
C2  - 24319
SP  - 174-185
TI  - The mouse Trm1-like gene is expressed in neural tissues and plays a role in motor coordination and exploratory behaviour.
JO  - Gene
VL  - 389
IS  - 2
PB  - Elsevier Science
PY  - 2007
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Using a versatile and highly sensitive retroviral microarray, we have investigated particle preparations from three different human packaging cell lines harboring retroviral vector systems based on human immunodeficiency virus (HIV) and murine leukemia virus (MLV). 293Rev/Gag/Poli cells inducibly express high titers of HIV-derived particles for packaging of HIV vectors. The Phoenix-GP and the Anjou 65 cell lines constitutively express MLV vector particles. We compared the transcription profiles of human endogenous retroviruses (HERVs) in all cell lines with the HERV sequences present in the particles. In addition, the influence of the transfected vector plasmid on the copackaging of HERVs was investigated. All particle preparations showed a defined pattern of endogenous retroviral sequences that differed from the cellular HERV expression pattern. HERV transcripts were observed in the particle preparations independent of whether a vector construct was coexpressed or not.
AU  - Zeilfelder, U.*
AU  - Frank, O.*
AU  - Sparacio, S.*
AU  - Schön, U.
AU  - Bosch, V.*
AU  - Seifarth, W.*
AU  - Leib-Mösch, C.
C1  - 4584
C2  - 24373
SP  - 175-179
TI  - The potential of retroviral vectors to cotransfer human endogenous retroviruses (HERVs) from human packaging cell lines.
JO  - Gene
VL  - 390
IS  - 1-2
PB  - Elsevier
PY  - 2007
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Guimera, J.
AU  - Vogt Weisenhorn, D.M.
AU  - Echevarria, D.*
AU  - Martinez, S.*
AU  - Wurst, W.
C1  - 3725
C2  - 23957
SP  - 65-76
TI  - Molecular characterization, structure and developmental expression of Megane bHLH factor.
JO  - Gene
VL  - 377
PY  - 2006
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Kramer-Hämmerle, S.
AU  - Hahn, A.*
AU  - Brack-Werner, R.
AU  - Werner, T.*
C1  - 1285
C2  - 23038
SP  - 31-38
TI  - Elucidating effects of long-term expression of HIV-1 Nef on astrocytes by microarray, promoter, and literature analyses.
JO  - Gene
VL  - 358
PY  - 2005
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Feederle, R.*
AU  - Delecluse, H.J.*
AU  - Rouault, J.P.*
AU  - Schepers, A.
AU  - Hammerschmidt, W.
C1  - 5214
C2  - 22374
SP  - 91-97
TI  - Efficient somatic gene targeting in the lymphoid human cell I DG75.
JO  - Gene
VL  - 343
PY  - 2004
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Kammerer, R.
AU  - Popp, T.*
AU  - Singer, B.B.*
AU  - Schlender, J.*
AU  - Zimmermann, W.*
C1  - 5290
C2  - 22383
SP  - 99-109
TI  - Identification of allelic variants of the bovine immune regulatory molecule CEACAM1 implies a pathogen-driven evolution.
JO  - Gene
VL  - 339
PY  - 2004
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Tallafuß, L.
AU  - Bally-Cuif, L.
C1  - 22099
C2  - 20757
SP  - 23-32
TI  - Formation of the head-trunk boundary in the animal body plan : An evolutionary perspective.
JO  - Gene
VL  - 287
PY  - 2002
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Krausz, E.
AU  - Graw, J.
C1  - 20759
C2  - 17629
TI  - A new cat reporter gene vector designed for rapid and efficient cloning of PCR products.
JO  - Gene
VL  - 177 99-102
PY  - 1996
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Zarbalis, K.
AU  - Chatterjee, B.
AU  - Löster, J.
AU  - Werner, T.
AU  - Graw, J.
C1  - 20760
C2  - 17634
SP  - 181-184
TI  - Sequence analysis of the beta B2-crystallin cDNA of hamster containing a domain conserved among vertebrates.
JO  - Gene
VL  - 174
PY  - 1996
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - The promoter of the murine γE-crystallin (γE-Cry) encoding gene (γ(E-cry) was analyzed for specific interactions with lenticular proteins in a gel-retardation assay. A 21-bp fragment immediately downstream of the transcription initiation site (DOTIS) is demonstrated to be responsible for specific interactions with lens extracts. The DOTIS-binding protein (s) accept only the sense DNA strand as target; anti-sense or double-stranded DNA do not interact with these proteins. The DOTIS sequence element is highly conserved among the murine γD-, γE- and γ F-cry and is present at comparable positions in the orthologous rat genes. Only a weak or even no protein-binding activity is observed if a few particular bases are changed, as in the rat γA-, γC- and γE-cry elements. DOTIS-binding proteins were found in commercially available bovine α-Cry preparations. The essential participation of α-Cry in the DNA-binding protein complex was confirmed using α-Cry-specific monoclonal antibody. The results reported here point to a novel function of α-Cry besides the structural properties in the lens.
AU  - Pietrowski, D.
AU  - Durante, M.J.
AU  - Liebstein, A.
AU  - Schmitt-John, T.
AU  - Werner, T.
AU  - Graw, J.
C1  - 40057
C2  - 38076
SP  - 171-178
TI  - α-Crystallins are involved in specific interactions with the murine γD/E/F-crystallin-encoding gene.
JO  - Gene
VL  - 144
IS  - 2
PY  - 1994
SN  - 0378-1119
ER  - 

TY  - JOUR
AU  - Graw, J.
AU  - Liebstein, A.
AU  - Pietrowski, D.
AU  - Schmitt-John, T.
AU  - Werner, T.
C1  - 20650
C2  - 13864
SP  - 145-156
TI  - Genomic Sequences of Murine ..B- and ..C-crystalling Genes and Complete Evolutionary Pattern of Mouse, Rat and Human ..-crystallins derived from exon 3.
JO  - Gene
VL  - 136
PY  - 1993
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - The murine genes, γB-cry and γC-cry, encoding the γB- and γC-crystallins, were isolated from a genomic DNA library. The complete nucleotide (nt) sequences of both genes were determined from 661 and 711 bp, respectively, upstream from the first exon to the corresponding polyadenylation sites, comprising more than 2650 and 2890 bp, respectively. The new sequences were compared to the partial cDNA sequences available for the murine γB-cry and γC-cry, as well as to the corresponding genomic sequences from rat and man, at both the nt and predicted amino acid (aa) sequence levels. In the γB-cry promoter region, a canonical CCAAT-box, a TATA-box, putative NF-I and C/EBP sites were detected. An R-repeat is inserted 366 bp upstream from the transcription start point. In contrast, the γC-cry promoter does not contain a CCAAT-box, but some other putative binding sites for transcription factors (AP-2, UBP-1, LBP-1) were located by computer analysis. The promoter regions of all six γ-cry from mouse, rat and human, except human ψγF-cry, were analyzed for common sequence elements. A complex sequence element of about 70-80 bp was found in the proximal promoter, which contains a γ-cry-specific and almost invariant sequence (crygpel) of 14 nt, and ends with the also invariant TATA-box. Within the complex sequence element, a minimum of three further features specific for the γA-, γB- and γD/E/F-cry genes can be defined, at least two of which were recently shown to be functional: In addition to these four sequence elements, a subtype-specific structure of inverted repeats with different-sized spacers can be deduced from the multiple sequence alignment. A phylogenetic analysis based on the promoter region, as well as the complete exon 3 of all γ-cry from mouse, rat and man, suggests separation of only five γ-cry subtypes (γA-, γB-, γC-, γD- and γE/F-cry) prior to species separation.
AU  - Graw, J.
AU  - Liebstein, A.
AU  - Pietrowski, D.
AU  - Schmitt-John, T.
AU  - Werner, T.
C1  - 40271
C2  - 38994
SP  - 145-156
TI  - Genomic sequences of murine γB- and γC-crystallm-encoding genes: promoter analysis and complete evolutionary pattern of mouse, rat and human γ-crystallins.
JO  - Gene
VL  - 136
IS  - 1-2
PY  - 1993
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - We tested the effect of the immunoglobulin (Ig) heavy- and κ-chain 3' enhancers on the expression of Ig genes in B-cells. Inclusion of the heavy-chain 3' enhancer in addition to the μ intron enhancer increased the expression rate up to sixfold, but this effect was strongly position dependent, in that it was only observed when the element was located downstream from the constant exons. Furthermore, the stimulatory effect could be augmented by increasing the distance between the constant gene segments and the 3' enhancer. When the 3' enhancer was located upstream from the variable gene promoter, the transcription was dramatically suppressed. Thus, the heavy-chain 3' enhancer does not fit into the usual definition of an enhancer element. The implications for the production of recombinant antibodies are discussed.
AU  - Mocikat, R.
AU  - Harloff, C.
AU  - Kütemeier, G.
C1  - 40260
C2  - 40007
SP  - 349-353
TI  - The effect of the rat immunoglobulin heavy-chain 3' enhancer is position dependent.
JO  - Gene
VL  - 136
IS  - 1-2
PY  - 1993
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - Cathepsin B-encoding cDNA (CTSB) clones have been isolated from a λgt10 library of a murine osteosarcoma by differential screening during a search for genes which are typically expressed during osteogenic differentiation in mouse mandibular condyles in vitro. Sequencing of the CTSB 3' end revealed that the isolated sequence contained an 825-bp 3'-noncoding region, the polyadenylation signal and the poly(A) tail. The enhanced CTSB expression during the early stages of the enchondral ossification-like process in mandibular condyles in vitro suggests that CTSB participates in the degradation of cartilage matrix prior to the synthesis of bone matrix proteins.
AU  - Friemert, C.
AU  - Closs, E.I.
AU  - Silbermann, M.H.
AU  - Erfle, V.F.
AU  - Strauß, P.G.
C1  - 40820
C2  - 12165
SP  - 259-261
TI  - Isolation of a cathepsin B-encoding cDNA from murine osteogenic cells.
JO  - Gene
VL  - 103
IS  - 2
PY  - 1991
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - The murine γE-crystallin-encoding gene (γE-cry) was isolated from a genomic DNA library. The nucleotide (nt) sequence was determined of 1100 bp upstream from the first exon to the polyadenylation site, comprising more than 3600 bp. The gene was characterized by phylogenetic nt sequence analysis in context with the already described γ-cry genes from rat, mouse and human. The γE-cry genes (mouse and rat) are clearly separate from the corresponding γE-cry genes. Based on the phylogeny, the discussion about the murine γ2-cry classification as γF-cry [Bloemendal et al., Exp. Eye Res. 48 (1989) 465-466] is resolved. The murine γE-cry gene has characteristics similar to other genes from the γ-cry gene family, except for an 18-fold repeat of the sequence, 5'-CTCAG, located at the 3'-end of intron B. There is no similar repeat structure in any other γ-cry gene. No binding site for a common transcription factor could be detected among the 1100 bp of the 5'-region.
AU  - Graw, J.
AU  - Coban, L.
AU  - Liebstein, A.
AU  - Werner, T.
C1  - 40763
C2  - 38671
SP  - 265-270
TI  - Murine γE-crystallin is distinct from murine γ2-crystallin.
JO  - Gene
VL  - 104
IS  - 2
PY  - 1991
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - We have cloned by the polymerase chain reaction a 2.1-kb fragment carrying heavy-chain joining (J(H)) gene segments and a part of the J(H)-C(μ) intron of the rat. Sequencing showed that the rat genome has four functional J(H) segments and that only a slight divergence has occurred after the separation of rat and mouse. A systematic sequence comparison between the two species and human revealed an additional J(H) pseudogene in rat and mouse 5' of J(H)1 which has not been described so far. The implications in evolutionary terms are discussed. In addition, we give an assessment of the misincorporation rate of the Taq polymerase.
AU  - Lang, P.
AU  - Mocikat, R.
C1  - 40801
C2  - 38041
SP  - 261-264
TI  - Immunoglobulin heavy-chain joining genes in the rat: Comparison with mouse and human.
JO  - Gene
VL  - 102
IS  - 2
PY  - 1991
SN  - 0378-1119
ER  - 

TY  - JOUR
AB  - We have cloned a region of repetitive DNA from the phytopathogenic fungus, Phytophthora parasitica. The cloned region consists of 17 highly homologous units arranged in tandem. The consensus sequence is 562 bp long and carries the information for a tRNAAsp. All sequence motifs required for efficient RNA polymerase HI transcription are present, and the tRNA derived from the nucleotide sequence is able to form a complete cloverleaf structure with high homology to previously characterized tRNAAsp molecules. The isolated tRNAAsp gene cluster is located at a distance of 20 kb from the TRP1 gene of P. parasitica. It comprises about 0.1 % of the total genomic DNA. Similar clusters were detected in four other Phytophthora species.
AU  - Rump, A.
AU  - Karlovsky, P.
C1  - 40755
C2  - 38923
SP  - 51-56
TI  - Tandem arrangement of tRNAAsp-encoding genes in Phytophthora spp.
JO  - Gene
VL  - 102
IS  - 1
PY  - 1991
SN  - 0378-1119
ER  -