- Research Interest
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DELIVER - Decipher unExpLored genetIc Variation inrEproductive failuRe
We aim at understanding the contribution of genomic variants to the failure of early human embryonic development. Past and current research in this context investigates mostly aneuploidies or insertion/deletions of few up to 10Mb, leaving unexplored the two extremes of this range, i.e. small-size and very large structural variants. We focus on this unexplored variation analyzing DNA sequence data from euploid miscarried embryos produced with third generation sequencing and analyzed with pangenomic techniques. The third-generation sequencing produces reads of length suitable to confidently discover large structural variants, while the pangenome analysis enables the discovery of variants not present in the reference sequence, and highly likely to be detrimental.
We are interested in sequencing euploid embryos from miscarriages, therefore we do a pre-sequencing screening to exclude aneuploidies and comorbidities. Euploid embryos are sequenced and sequences are used to identify mutations. We expect that highly deleterious dominant mutations as well as rare moderately to highly deleterious recessive mutations contribute to miscarriage. Participant inclusion criteria (e.g. recurrence, consanguinity, selection of comorbidities) will ensure the prevalence of genetic over environmental causes.
HD-DittoGraph - a digital human Embryonic Stem Cell platform for Hungtinton’s repeats
This project aims to identify the genetic factors that are implicated in instability of the CAG repeats in the Hungtinton’s gene HTT, both during mitotic cell replication and in post-mitotic neurons. We use a human embryonic stem (hES) cellC-based cell platform, barcoded DNA libraries, CRISPR technologies and long-read third generation DNA sequencing.
This project is in collaboration with: Elena Cattaneo and Dario Besusso, University of Milano, Italy - Allegra Via- ELIXIR-IIB Training Platform
Mouse Pangenomics
The members of BXDs family have been inbred for 20-200 generations. They are of great value for mapping complex traits and phenome-wide association analysis. Current genomic studies on BXD assume a single linear reference genome, making it difficult to observe sequences diverging from the reference, therefore limiting the accuracy and completeness of analyses. Pangenome models overcome this limitation as they contain the full genomic information of a species.
We are building a reference pangenome for all extant members of all BXD families leveraging third generation and 10X sequence data. We will analyze the genetic variation in relation to thousands of phenotypes in the GeneNetwork
(A) odgi-vizlinear visualization of the pangenome of chromosome 19. Each line represents a haplotype. Line interruptions (white) are insertions in one or more strains, therefore deletions in the others (vertical white stripes). The left side is the centromere, the right side is the telomere.In these two regions sequences are fragmented. (B) Extract of the pangenome from the Zfp91gene showing a 2,006 bp insertion found in DBA/2J and 48% of the BXD strains(green nodes in the graph). The insertion is in complete linkage with two other insertions of 4 bp and 135 bp in a region spanning 2.8 kbp.(C) Strain-specific haplotypes (gray segments are not in scale)
This project is in collaboration with - Robert Williams , David Ashbrook, Pjotr Prins, Erik Garrison, Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center. Memphis, TN
PARDOM - Domestications of Phaseolus
Phaseolus is a unique example of multiple parallel domestication events that provide a natural experiment to study convergent phenotypic evolution associated with convergent genomic and/or transcriptomic changes. With the project PARDOM (Parallel Domestications: the Phaseolus replicated experiment to understand genome evolution and adaptation), we want to study convergent evolution in four replicates of the domestication process in P. vulgaris (PV) and P. lunatus (PL), two highly collinear species each domesticated independently in Mesoamerica and the Andes, resulting in at least four independent domestication events.
This project is in collaboration with: - Roberto Papa
I am a genomicist and an expert in human evolutionary and population genomics and bioinformatics.
I graduated in Evolutionary Biology from the University of Naples Federico II and did postdoctoral research at the University of Ferrara (Italy) and at Wellcome Trust Sanger Institute in Cambridge (UK). I am now leading the Population genomics laboratory at the IGB-CNR (Naples, Italy) and I am Assistant Professor at the University of Tennessee, College of Medicine, in the Department of Genetics, Genomics and Informatics
In my postdoctoral research I was part of the international consortium 1000 Genomes[PMID: 26432245; 23128226] where I led contributions to two specific aspects. First, I contributed to develop FunSeq [PMID: 24092746], a tool that integrates non-coding information from relevant biological databases for the functional characterization of non-coding variants. Second, I lead a genome-wide scan to identify genomic regions with exceptionally high levels of population differentiation [PMID: 24980144] demonstrating that these regions are enriched for positive selection events and that one half may be the result of classic selective sweeps. Findings from both sub-projects have since been applied to demographic inference and the molecular diagnosis of cancer and myeloid malignancies [PMID: 27121471, 22446628], and to deeper studies on positive selection at the ABCA12 gene [PMID: 30890716].
During my PhD I worked on human isolated populations contributing to characterize several isolated populations, describing the genomic consequences of isolation [PMID: 17476112, 19550436, 22713810], contributing to genetic association studies [PMID: 16611673, 18162505] and to characterize rare variation [PMID: 28643794]
silvia.buonaiuto@igb.cnr.it
Project Title: DELIVER - Decipher unExpLored genetIc Variation inrEproductive failuRe.
My project studies idiopathic recurrent miscarriage to identify genetic variants likely to be causative and ultimately improve prenatal diagnosis. I have a PhD degree From the university Luigi Vanvitelli, a master’s degree in Biology from the University of Napoli Federico II. I did a master thesis in molecular biology at the Department of Biology.
madeleine.emms@igb.cnr.it
Project Title: PARDOM, Parallel Domestications: the Phaseolus replicated experiment to understand genome evolution and adaptation.
Two species in the genus Phaseolus have been domesticated independently in both Mesoamerica and the Andes, representing multiple parallel domestication events and so providing a natural experiment to study convergent evolution using population genetics. I am also finishing my PhD in Zoology at the University of Cambridge, UK, where I used population genetics to determine the population response of coral reef fishes to climate-induced habitat loss by looking back to the Last Glacial Maximum. I have an MSc in Marine Science from King Abdullah University of Science and Technology (KAUST), Saudi Arabia, and a BSc in Marine Biology from the University of St. Andrews (Scotland). I also worked for several NGOs in coral reef conservation and education prior to starting my PhD.
gianluca.damaggio@igb.cnr.it
Project Title: HD-DittoGraph - a digital human Embryonic Stem Cell platform for Hungtinton’s repeats .
My project aims at acquiring the ability to precisely detect perturbations of short tandem repeats of the Huntington’s gene in proliferative cells, leveraging third-generation sequencing data. Currently, I am a PhD student at the University of Naples Federico II, visiting student at the IGB-CNR in Naples, and a Junior Research Fellow at the University of Milano Statale in the Laboratory of Elena Cattaneo
fvillan1@uthsc.edu
Project Title: Mouse Pangenomics
I am building the pangenome of inbred mice using third generation sequence data. I am a PhD student at the University of Tennessee. I have a master degree in Biology from the University of Salerno (Italy).
Project Title: Gene expression regulation through methylation in the genome of human embryos (in collaboration with Marialaura Zitiello)
Project Title: Deciphering the role of structural variation in miscarried embryos
The aim of my project is to investigate the contribution of structural variation to the genetic causes of euploid miscarriages. I use short-reads sequence data from ten miscarried embryos to call structural variants (SV) using the method developed by Sirén et al. (Science 374.6574 (2021): abg8871). To complete the analysis, I will integrate functional information from genomic annotations to understand to which extent SV can cause miscarriages.
Project Title: Gene expression regulation through methylation in the genome of human embryos (in collaboration with Antonella Mecca)