The Medical Genetics Laboratory has a well-established tradition of biomedical research in the various areas pertaining to the discipline and in support of other topics, such as understanding the biological basis of cancer.
Currently, the main research topics involve:
- Advanced diagnostics based on a multi-omics platform for the study of rare and neurodevelopmental diseases. The integrated diagnostic platform combines long-read sequencing, ultra-deep sequencing, RNA sequencing, whole-exome sequencing, and DNA methylation profiling to resolve genetically unsolved cases. The multi-omics approach allows the identification of complex structural variants, mosaicisms, and epigenetic alterations undetectable by conventional methods, improving diagnostic yield and clinical interpretation from a precision medicine perspective with a special focus on neurofibromatosis.
- Epigenomics and phenotypic modulation in neurodevelopmental disorders. The laboratory studies the role of DNA methylation as a modulator of clinical expressivity in chromatinopathies and neurodevelopmental disorders. Through DNA methylation profiling and advanced bioinformatics analysis, disease-specific episignatures are defined and correlated with phenotypic severity, supporting variant interpretation and diagnostic stratification.
- Precision medicine in genetic syndromes from predisposition to cancer development. The laboratory has developed an integrated multi-omics profiling program in rare cancers and inherited cancer predisposition syndromes, combining germline and somatic Whole Exome Sequencing, tumor methylation analysis, and spatial transcriptomics to identify molecular drivers and prognostic biomarkers. Tissue characterization is complemented by liquid biopsy (ctDNA ultra-deep sequencing, fragmentomic and methylomic analysis, and miRNA profiling) for dynamic disease monitoring.
- Functional genetics in Mendelian genodermatoses. This line of research is focused on understanding altered molecular networks in genodermatoses, with a focus on Darier Disease and ATP2A2-NOTCH1 interaction. The approach integrates genomics, transcriptomics, patient-specific cell cultures, and in vitro functional assays to define genotype-phenotype correlations and potential therapeutic targets.
- Genetics of psychiatric disorders and polygenic risk modeling. The laboratory in collaboration with the UO of Psychiatry, applies polygenic risk models (PRS) to identify biologically distinct subtypes in complex psychiatric disorders, particularly obsessive-compulsive disorder and bipolar disorder. The integration of genome-wide genotyping, functional analysis, and clinical data allows delineating different genetic trajectories and promoting precision medicine approaches in psychiatric settings.
Main methodologies applied:
- Nucleic acid extraction, Real Time PCR and Sanger Sequencing
- Germinal and somatic Whole Exome Sequencing (WES)
- Long-read sequencing using MinIon and PromethIon (Oxford Nanopore Technologies)
- Ultra-deep targeted sequencing (up to 20,000-30.000X)
- Genome-wide SNP genotyping, GWAS-based analysis, and Polygenic Risk Score (PRS) analysis
- RNA Sequencing (RNA-Seq)
- High-resolution Spatial Transcriptomics
- DNA methylation profiling (Illumina Infinium EPIC array)
- Fragmentomics and methylomics analysis on ctDNA
- Liquid biopsy (ctDNA/ctRNA sequencing, miRNA profiling)
- Patient-specific primary cultures
- In vitro functional assays (Western blot, qPCR, Luciferase assays, ATP-based cell viability assays)
- Artificial Intelligence and Machine Learning-based predictive models for multi-omics integration and clinical stratification
Main Equipment:
- MiSeq Illumina next-generation sequencer,
- NextSeq550dX Illumina next-generation sequencer
- NextSeq2000 Illumina next-generation sequencer
- Applied Biosystems Sanger sequencer
- Sanger long-read MinIon and PromethIon ONT
- Infinium array scanner for methylation NextSeq550dX Illumina
- Roche 480 Real Time PCR
- Thermal cyclers
- Agilent 4200 TapeStation System for library quantification NGS
- Maxwell 16 system Promega nucleic acid and protein extractor and MagCore Plus Diatech
- Nanondrop One Thermo Scientific
- Qubit Thermo Fisher fluorometer
Keywords
Genomics, molecular genetics, epigenetics, next-generation sequencing, rare diseases, genotype/phenotype.
