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]