Ana Paula Castro

Carmen Torres

Gilberto Igrejas

Isabel Carvalho

José António Antonio Carvalho

Patrícia Poeta

Sandra Martínez-Álvarez

English

Ana Paula Castro [0000-0002-9576-2184]

Carmen Torres [0000-0003-3709-1690]

Repositorio de Universidad de La Rioja

Cenci Bolognetti (to F.C.); “Progetti per Avvio alla Ricerca - Tipo 1”,Sapienza University of Rome (to E.D’A.).M. Bonito: None. E. D’Atanasio: None. F. Ravasini: None. S.Cariati: None. B. Bonucci: None. A. Finocchio: None. A.Novelletto: None. F. Cruciani: None. B. Trombetta: None.P20 Functional Genomics and EpigenomicsP20.001.D Investigating the meaning of age-related changesin DNA methylation by studying the correlation betweenepigenetic age acceleration and progressive human appear-ance traitsRezvan Noroozi1, Aleksandra Pisarek1, Joanna Rudnicka1, MichałBoroń2, Kamila Migacz-Gruszka3, EPIGENOME Consortium, AnetaSitek4, Andrzej Ossowski5, Wojciech Branicki1,2, Magdalena Spól-nicka2, Ewelina Pośpiech11Malopolska Centre of Biotechnology, Jagiellonian University,Kraków, Poland, 2Central Forensic Laboratory of the Police, Warsaw,Poland, 3Department of Dermatology, Collegium Medicum of theJagiellonian University, Kraków, Poland, 4Department of Anthropol-ogy, Faculty of Biology and Environmental Protection, University ofŁódź, Łódź, Poland, 5Department of Forensic Genetics, PomeranianMedical University in Szczecin, Szczecin, Poland.Introduction: DNA methylation markers have been proposed as apredictor of biological age. At the same time, phenotypic aging isa potential model for exploring the molecular mechanisms ofaging. By investigating the correlation between epigenetic ageacceleration (EAA) and externally visible phenotypes we aim toinvestigate molecular pathways involved in aging processes anddisclose promising targets for antiaging therapies.Materials and Methods: A cohort of about 1000 individuals ofEuropean descent with described physical phenotype andcollected lifestyle information will be examined using Infinium®Global Screening Array and Infinium® MethylationEPIC 850Kmicroarray. DNA methylation data will be examined using variousage prediction models to calculate EAA. The EAA values will befurther correlated with phenotypic traits including hair loss, hairgreying, and wrinkles formation as well as with genetic variation.Results and Conclusion: The study will improve our under-standing of the role of interactions between genes, DNAmethylation, and EAA in determining age-related appearancetraits. We will assess the heritability of the aging rate and measurethe importance of environmental factors for accelerated aging.The role of individual CpG and SNP markers will be tracked inenrichment analysis. The study will have practical value inforensics by developing prototype predictive models for specificage-related features based on genetic and epigenetic information,as well as may find practical application in the cosmetic industryby developing products to prevent or slow down phenotypicaging. This research was supported by the grant from the NationalCentre for Research and Development no DOB-BIO10/06/01/2019.R. Noroozi: None. A. Pisarek: None. J. Rudnicka: None. M.Boroń: None. K. Migacz-Gruszka: None. A. Sitek: None. A.Ossowski: None. W. Branicki: None. M. Spólnicka: None. E.Pośpiech: None.P20.002.A A multi-omics approach to study monozygotictwins discordant for amyotrophic lateral sclerosisMartina Tosi1, Miriam Zuccalà1, Francesco Favero1, Lucia Corrado1,Roberta Croce1, Chiara Basagni1, Nadia Barizzone1, Laura Follia2,Fabiola De Marchi3, Elena Chinni4, Letizia Mazzini3, Davide Corà1,Maurizio Leone4, Sandra D’Alfonso11University of Eastern Piedmont UPO, Novara, Italy, 2University ofTorino, Torino, Italy, 3ALS Center AOU Maggiore della Carità, Novara,Italy, 4SC Neurologia, Dipartimento di Scienze Mediche, IRCCS CasaSollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerativedisease, characterised by progressive death of upper and lowermotor neurons. The majority of ALS cases are sporadic, while 10%are familial. ALS aetiology is still not completely understood. Toinvestigate genetic and epigenetic factors underlying ALS, westudied a monozygotic twin pair discordant for ALS with a multi-omics approach combining whole exome sequencing withgenome-wide methylome- and transcriptome data from wholeblood and PBMCs. For methylation, we used the IlluminaEPICArray which covers 850,000 methylations sites and theChaAMP software for the analyses, while for gene expressionstudy, Illumina TruSeq Stranded mRNA sequencing was per-formed. The results were considered independently and incombination to identify disease-relevant methylation changesand their downstream impact. Twins tested negative for muta-tions in main ALS-genes. We identified 59 differentially expressedgenes (DEGs) (p.adj < 0.1; |log2FC| >1) involved in immune systempathways. After QC, we found 2 differentially methylated probes(pvalue adj ≤ 0.1) in CACNA1G, expressed mostly in brain, andVAX1 genes; while filtering by delta beta (Δβ) values, we identified2 probes with Δβ ≤ - 0.25 (in an intergenic region and RUSC1-AS1)and 2 probes with Δβ ≥ 0.25 (in AARS and KPNA4). None of themfell into the highlighted DEGs. Finally, mRNA-seq results werecompared with larger literature datasets. Further comparativeanalyses on external epigenetic datasets as well as CNV and SNVanalyses on exome data are ongoing to elucidate possibleepigenetic and somatic genetic factors that could underliesusceptibility to sporadic ALS.M. Tosi: None. M. Zuccalà: None. F. Favero: None. L. Corrado:None. R. Croce: None. C. Basagni: None. N. Barizzone: None. L.Follia: None. F. De Marchi: None. E. Chinni: None. L. Mazzini:None. D. Corà: None. M. Leone: None. S. D’Alfonso: None.P20.003.B Resistance profile and genetic diversity amongselected ESBL-producing Escherichia coli isolates from urocul-tures in a portuguese hospitalIsabel Carvalho1,2,3,4,5, José António António Carvalho6, Ana PaulaCastro6, Sandra Martínez-Álvarez5, Gilberto Igrejas2,3,4, CarmenTorres5, Patrícia Poeta1,41Microbiology and Antibiotic Resistance Team (MicroART), Depart-ment of Veterinary Sciences, University of Trás-os-Montes and Alto-Douro), Vila Real, Portugal, 2Department of Genetics and Biotechnol-ogy, UTAD, Vila Real, Portugal, 3Functional Genomics and ProteomicsUnit, UTAD, Vila Real, Portugal, 4Laboratory Associated for GreenChemistry (LAQV‐REQUIMTE), New University of Lisbon, Monte daCaparica, Portugal, 5Area Biochemistry and Molecular Biology,University of La Rioja, Logroño, Spain, 6Medical Center of Trás-os-Montes e Alto Douro E.P.E., Vila Real, Portugal.Introduction: Antimicrobial-resistant bacteria are contributing tomortality and morbidity worldwide. The Extended-Spectrumβ-lactamase-producing E. coli is considered one of the greatconcerns regarding the public health issue. The purpose of thiswork was to determine prevalence and genetic characteristics ofselected ESBL-producing E. coli isolates from urinary infections.Materials and Methods: Twenty cefotaxime/ceftazidime-resis-tant E. coli isolates were obtained aleatory from urocultures in aPortuguese hospital, during June 2017-July 2018. Identificationwas performed by MALDI-TOF MS. Antimicrobial susceptibilityAbstracts from the 54th European Society of Human Genetics (ESHG) Conference541European Journal of Human Genetics (2022) 30:88 – 608against 13 antibiotics was analyzed by disk diffusion test.Screening of ESBLs was performed and resistance genes wereanalyzed by PCR/sequencing. Phylogenetic grouping was alsoperformed by multiplex-PCR.Results: ESBL-production was detected in 90% of the isolates(18/20), mostly associated with CTX-M-15 (n= 13) and CTX-M-1 (n= 1) enzymes. Tetracycline resistance was associated with tetA (n= 5) and tetB (n= 3). The most common phylogenetic groupamong ESBL-producers was B2 (n= 13), followed by D (n= 2), C(n= 1) and A (n= 1). The isolates carrying the blaCTX-M-15 genewere ascribed to phylogroups B2 and D, and the blaCTX-M-1-carrying isolate was typed as phylogroup C. The two ESBL-negative E. coli isolates also carried a CTX-M gene (which variantwas not determined).Conclusions: These findings indicate that the CTX-M-15enzyme is the main mechanism of ESBL-production amongurinary infections isolates in our hospital, being these isolates ofthe phylogroups B2 and D.Acknowledgments: First author - FCT through PhD grant SFRH/BD/133266/2017 (Medicina Clínica e Ciências da Saúde); ProjectSAF2016-76571-R from AEI (Spain) and FEDER of EU; LAQV - FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020).I. Carvalho: None. J.A. Carvalho: None. A.P. Castro: None. S.Martínez-Álvarez: None. G. Igrejas: None. C. Torres: None. P.Poeta: None.P20.004.C E6 and E7 HPV16 oncogenes influence genetranscription trough the genome-wide pattern deposition ofMBD2,3 components of NuRD nucleosome remodelingcomplexAnca Botezatu, Adriana Plesa, Iulia V. Iancu, Marinela Bostan, MirelaMihaila, Adrian Albulescu, Alina fudulu, Carmen C. Diaconu, GabrielaAntonInstute of Virology "St.S.Nicolau", Bucharest, Romania.Human papilloma virus (HPV) is the etiologic agent of cervicalcancer and the third most commonly diagnosed type of cancerin women worldwide. The nucleosome remodelling anddeacetylation complex (NuRD) is a group of associated proteinswith ATP-dependent chromatin remodelling and histonedeacetylase activities. MBD2/3 proteins from NuRD complexexhibit methyl-CpG-binding domains, which mediate an inter-action with methylated DNA. The current study aims to assessthe viral oncogenes influence on the MBDs overall bindingpattern to CpG islands. ChIP-Seq for MBD2/3 genome wideDNA binding pattern (e.g. promoters, gene control region,transcriptional enhancers, etc.) in untreated and HPV 16 E6/E7shRNAs treated CaSki cell culture was performed and theresults were analysed using Base Space Illumina apps. MBD2/3proteins were localized at the level of intron, intergenic regionsand TSS. After ChIP-Seq peak score analysis, a cut-off of 9 wasestablish and 54 gene loci were identified. The correspondinggenes were further analysed in qRT-PCR and their expressionwas found to be deregulated. When both oncogenes (E6 andE7) were silenced, we noted an enrichment of MBD2/3 proteinsat CDK6, DLC1, NRIP1 gene loci involved in oestrogen receptor(ER) signalling pathway. Another interesting gene loci involvedin mRNA processing and cancer growth and metastasis wereidentified (EIF4G3 and DCP2). Viral oncogenesact synergistically on the gene transcription pattern byinteracting with the MBD2/3 proteins of NuRD complex.Epigenetic gene control is a complex phenomenon that isguided by internal, cellular and external factors as well as viralinfections. Acknowledgments: TE39/2020A. Botezatu: None. A. Plesa: None. I.V. Iancu: None. M.Bostan: None. M. Mihaila: None. A. Albulescu: None. A. fudulu:None. C.C. Diaconu: None. G. Anton: None.P20.005.D New cis-regulatory elements modulate CFTRexpressionMégane COLLOBERT1, Ozvan Bocher1, Anaïs Le Nabec1, Emma-nuelle Génin2, Claude Férec1,3, Stéphanie Moisan1,31Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France, 2Inserm, UnivBrest, EFS, UMR 1078, GGB, Brest, France, 3Univ Brest, CHRU Brest,UMR 1078, Brest, France.8% of the human genome is covered with candidate cis-regulatoryelements (cCREs). Anomalies of CREs at distance from a gene havebeen identified as being involved in various genetic diseases.Although, more than 2100 variants have been detected in CysticFibrosis Transmembrane conductance Regulator (CFTR) gene,responsible of Cystic Fibrosis (CF) or CFTR-related disorders, somepatients have an incomplete genotype or present extremesphenotypes. Development of chromatin conformation studytechniques identified several long-range regulatory elements ofCFTR gene. Our aim is to highlight the role and involvement ofregulatory elements on the architecture and conformation of theCFTR gene.GWAS3D score application allowed us to highlightinvolvement of four CFTR introns in gene regulation, introns 26(4374+ 1,3 kb), 24 (4095+ 7,2 kb), 1 (185+ 10 kb) et 12 (1811+0,8 kb). Introns 1 and 12 have already been described as two maincooperative CFTR CREs in intestinal cells. Activity tests in Caco-2intestinal cells show strong cooperative effects of the fourpredicted introns on CFTR promoter activity. Chromatin immuno-precipitation analyses demonstrate enrichment of a large networkof keys transcription factors (TFs) in intestinal cells, such HNF1a,p300, FOXA1/A2, CDX2 and TCF4, in introns 24 and 26 enhancers.In conclusion, two new CREs with cooperative enhancer activitieshave been identified, enriched with important TFs, redefining the3D regulation model of the CFTR gene in intestinal cells. Ongoingstudies of chromatin conformation and CRISPR interference willfurther characterize the role of these new enhancers.M. Collobert: None. O. Bocher: None. A. Le Nabec: None. E.Génin: None. C. Férec: None. S. Moisan: None.P20.006.A Functional characterisation of GJB2 cis regulatoryelements and WGS of heterozygous patients with NSHLAnaïs LE NABEC1, Mégane Collobert1, Alicia Quillévéré1, Cédric LeMaréchal1,2, Claude Férec1,2, Stéphanie Moisan1,21Univ Brest, Inserm, EFS, UMR 1078, GGB, brest, France, 2Univ Brest,CHRU Brest, UMR 1078, Brest, France.Three-dimensional chromatin organization plays a key role ongene expression. Gene regulation depends on cis-regulatoryelements which can interact with gene promoter by chromatinloop. Alteration of chromatin architecture and/or cis-actingelements can lead to enhanceropathies. Several unelucidatednonsyndromic hearing loss and deafness 1 (DFNB1) cases carryingout only one heterozygous pathogenic mutation on Gap JunctionBeta 2 (GJB2) gene, led to strongly suggest the presence of distantcis-regulation. Thanks to chromatin conformation study, wepreviously identified several cis-regulatory elements which haveenhancer action and silencer effect on GJB2 expression. Analysis ofCTCF binding allowed to purpose a DFNB1 3D looping model. Weidentified cooperative effects between enhancers. To confirm anAbstracts from the 54th European Society of Human Genetics (ESHG) Conference542European Journal of Human Genetics (2022) 30:88 – 608

Resistance profile and genetic diversity among selected ESBL-producing Escherichia coli isolates from urocultures in a portuguese hospital

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Resistance profile and genetic diversity among selected ESBL-producing Escherichia coli isolates from urocultures in a portuguese hospital

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