Vincenza Colonna

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Vincenza Colonna

Researcher

  +39 081 6132 254  

   vincenza.colonna@igb.cnr.it, vcolonna@uthsc.edu, enza.colonna@gmail.com 

Population Genetics and Genetic Epidemiology

Keywords: population genomics

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

Prioritization  of  putatively  detrimental  variants  in  euploid  miscarriages. Buonaiuto S, Biase ID, Aleotti V, Ravaei A, Marino A, Damaggio G, Chierici M, Pulijala M, D’AmbrosioP, Esposito G, Ayub Q, Furlanello C, Greco P, Capalbo A, Rubini M, Biase SD, Colonna V. Sci Rep.  2022 12(1):1997.   doi:10.1038/s41598-022-05737-3.  PMID: 35132093; PMCID: PMC8821623.
 
Efficient dynamic variation graphs  Eizenga J, Novak A, Kobayashi E, Villani F, Cisar C, Heumos S, Hickey G, Colonna V, Paten B, Garrison E Bioinformatics 2021 Jan 29;36(21):5139-5144. doi:10.1093/bioinformatics/btaa640. PMID: 33040146; PMCID: PMC7850124.
 
Genomic diversity and novel genome-wide association with fruit morphology in Capsicum, from 746kpolymorphic sites  Colonna V, D’Agostino N, Garrison E, Albrechtsen A, Jonas Meisner J, Facchiano A, Cardi T, TripodiP. Sci Rep. 2019 Jul 11;9(1):10067. doi: 10.1038/s41598-019-46136-5. PubMedPMID: 31296904
 
Positive selection in Europeans and East-Asians at the ABCA12 gene. Sirica R, Buonaiuto M, Petrella V, Sticco L, Tramontano D, Antonini D, Missero C, Guardiola O,Andolfi G, Kumar H, Ayub Q, Xue Y, Tyler-Smith C, Salvemini M, D’Angelo G, Colonna V Sci Rep. 2019 Mar 19;9(1):4843. doi:10.1038/s41598-019-40360-9. PubMed PMID: 30890716
 
Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated Europeanpopulations. Xue Y, Mezzavilla M, Haber M, McCarthy S, Chen Y, Narasimhan V, Gilly A, Ayub Q, Colonna V,Southam L, Finan C, Massaia A, Chheda H, Palta P, Ritchie G, Asimit J, Dedoussis G, Gasparini P,Palotie A, Ripatti S, Soranzo N, Toniolo D, Wilson JF, Durbin R, Tyler-Smith C, Zeggini E. Nat Commun. 2017 Jun 23;8:15927. PubMed PMID: 28643794
 
A global reference for human genetic variation. 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, KorbelJO, Marchini JL, McCarthy S, McVean GA, Abecasis GR. Nature. 2015 Oct 1;526(7571):68-74. PubMed PMID: 26432245
 
Genetic landscape ofpopulations along the Silk Road: admixture and migration patterns. Mezzavilla M, Vozzi D, Pirastu N, Girotto G, d’Adamo P, Gasparini P, Colonna V. BMC Genet. 2014 Dec 5;15:131.PubMed PMID: 25476266
 
Human genomic regions with exceptionally high levels of popula-tion differentiation identified from 911 whole-genome sequences. Colonna V, Ayub Q, Chen Y, Pagani L, Luisi P, Pybus M, Garrison E, Xue Y, Tyler-Smith C; 1000Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, HandsakerRE, Kang HM, Marth GT, McVean GA.Genome Biol. 2014 Jun 30;15(6):R88.doi: 10.1186/gb-2014-15-6-r88. PubMed PMID: 24980144
 
Integrative annotation ofvariants from 1092 humans: application to cancer genomics. Khurana E*, Fu Y*, Colonna V*, Mu XJ*, Kang HM, Lappalainen T, Sboner A, Lochovsky L, Chen J,Harmanci A, Das J, Abyzov A, Balasubramanian S, Beal K, Chakravarty D, Challis D, Chen Y, ClarkeD, Clarke L, Cunningham F, Evani US, Flicek P, Fragoza R, Garrison E, Gibbs R, G ̈um ̈us ZH, HerreroJ, Kitabayashi N, Kong Y, Lage K, Liluashvili V, Lipkin SM, MacArthur DG, Marth G, Muzny D,Pers TH, Ritchie GR, Rosenfeld JA, Sisu C, Wei X, Wilson M, Xue Y, Yu F; 1000 Genomes ProjectConsortium, Dermitzakis ET, Yu H, Rubin MA, Tyler-Smith C, Gerstein M. Science. 2013 Oct 4;342(6154):1235587.doi: 10.1126/science.1235587. PubMed PMID: 24092746
 
Small effective population size andgenetic  homogeneity  in  the  Val  Borbera  isolate. Colonna V, Pistis G, Bomba L, Mona S, Matullo G, Boano R, Sala C, Vigan`o F, Torroni A, Achilli A,Hooshiar Kashani B, Malerba G, Gambaro G, Soranzo N, Toniolo D.Eur J Hum Genet. 2013 Jan;21(1):89-94.  PubMedPMID: 22713810
 
 
An integrated map of genetic variation from 1,092human genomes. 1000 Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM,Handsaker RE, Kang HM, Marth GT, McVean GA. Nature. 2012 Nov 1;491(7422):56-65. PubMed PMID: 23128226
 
IFITM3 restricts the morbidity and mortality associated with influenza. Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ,Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, XueY,  Colonna V,  Tyler-Smith  C,  Dunning  J,  Gordon x SB;  GenISIS  Investigators;  MOSAIC  Investigators,Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P. Nature.  2012 Mar 25;484(7395):519-23.  PubMed PMID: 2244662
 
A world in a grain of sand: human history from geneticdata. Colonna V, Pagani L, Xue Y, Tyler-Smith C Genome Biol. 2011 Nov 21;12(11):234. PubMed PMID: 22104725
 
Human genome diversity: frequently asked questions. Barbujani G, Colonna V. Trends Genet. 2010Jul;26(7):285-95. PubMed PMID: 20471132

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
Postdoctoral fellow

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
Postdoctoral fellow

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
PhD student

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

Flavia Villani
PhD student

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).

Antonella Mecca
Master student

Project Title: Gene expression regulation through methylation in the genome of human embryos (in collaboration with Marialaura Zitiello) 

Our project aims to understand how methylation contribute to miscarriages. To do so, we look for differences in methylation profile between miscarried and normal embryos. We analyze genome sequence data of two human embryos, one miscarried and one voluntary aborted, to identify and compare their methylation profiles. We use the long reads obtained from Nanopore sequencing technology.
Angela Sequino
Master student

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.

Marialaura Zitiello
Master student

Project Title: Gene expression regulation through methylation in the genome of human embryos (in collaboration with Antonella Mecca)

Our project aims to understand how methylation contribute to miscarriages. To do so, we look for differences in methylation profile between miscarried and normal embryos. We analyze genome sequence data of two human embryos, one miscarried and one voluntary aborted, to identify and compare their methylation profiles. We use the long reads obtained from Nanopore sequencing technology.