The study of the genetic component of neurological complex disorders has a relevant impact from a clinical and public health perspective.
The present Unit is involved in the different steps of epidemiological studies which specifically address this issue, from sample size assessment to patients’ recruitment, from wet laboratory work-flow to statistical analyses and interpretation of genetic data.
The availability of high throughput technology, including an Illumina platform, in the Unit allows to perform large case-control genome-wide association studies and to test the specific contribution of single nucleotide polymorphisms (SNPs) and copy number variation regions in the risk and prognosis of neurological complex diseases.
Projects are also available on the analysis of mRNA transcripts, including whole-genome expression studies and whole-genome micro-RNA transcripts analyses, which are in early phases.
1990-1996: Medical degree, University of Milan, Italy;
1997-2002: Residency in Neurology, Department of Neurology, Scientific Institute San Raffaele, Milan;
2001-2002: Master of science in epidemiology and biostatistics, Joseph L. Mailman School of public health, Columbia University, New York;
2001-2002: Post-doctoral fellowship, Epilepsy Family Study, Gertrude H. Sergievsky Center, Columbia University, New York, NY;
2003-2006: International PhD program in Molecular Medicine, Scientific Institute San Raffaele, Milan;
2003-2005: PhD student, Human Molecular Genetics Unit, Scientific Institute San Raffaele;
2004-2005: Post-doctoral fellowship, Department of Biostatistics and Genetic Epidemiology at the Serono Genetics Institute (SGI), Evry, France;
2006-ongoing: Physician scientist, Department of Neurology and Neuro-rehabilitation and Institute of experimental neurology (INSPE), Scientific Institute San Raffaele, Milan;
2008: Contract professor of “Neuroepidemiology and genetic epidemiology” at the “Università Vita e Salute”, Scientific Institute and University San Raffaele, Milan; contract professor of “neuroepidemiology” at the Residency school of Neurology.
1996 Magna cum laude graduation in Medicine at the University of Milan
1999 De Visart prize (University of Milan)
2006 Best of free communications – European Neurological Society (ENS) meeting
- Financial support:
Research Training Fellowship Epilepsy Foundation (November 2002-November 2003): Successful application (refused).
Progetto Giovani Ricercatori – Ministero della Salute (2008): Identification of genetic factors involved in primary progressive multiple sclerosis: a model of neuro-degeneration. P.I. Dott. Filippo Martinelli Boneschi (Ospedale San Raffaele).
Fondazione Italiana Sclerosi Multipla (FISM) (2008): Genetic and transcriptional analysis of DPP6: a novel candidate gene in primary progressive Multiple Sclerosis. P.I.: Dott. Filippo Martinelli Boneschi (Ospedale San Raffaele).
Fondazione Cariplo (2008): Nuovi marcatori farmacogenetici e diagnostici per la demenza di Alzheimer. P.I.: Dott. Diego Albani (Istituto di Ricerche Farmacologiche “Mario Negri”)
Author of more than 50 peer-reviewed publications.
Reviewer of the European Journal of Neurology, American Journal of Human Genetics, Journal of Neurological Sciences.
Our Unit is involved in several projects and approaches which are commonly aimed to disentangle the genetic component of complex neurological diseases.
Such disorders are highly prevalent in the general population, and they are determined by a combination of genetic and environmental risk factors, each with a low to moderate effect, contributing to the observed phenotype.
Multiple Sclerosis (MS), which is the most common inflammatory disorder of the central nervous system (CNS), and Alzheimer’s disease (AD), which is the most prevalent neuro-degenerative disorder, represent the two clinical entities which share the interest of the Unit. Additional projects are also available on migraine and stroke, but in early phases.
A case-control association approach is used, which compare the genetic architecture in terms of single nucleotide polymorphisms and copy-number variant regions (CNVs) in affected and unaffected individuals.
These studies involve several steps: 1) Phenotypic characterization. A careful clinical characterization is needed, and it is achieved with the strict collaboration of neurologists. Clinical database and data management is also mandatory to collect phenotypical parameters. 2) Wet-laboratory work-flow. The availability of an Illumina platform in our Unit allows to type candidate genomic regions, but also the entire genome using tagging single nucleotide polymorphisms (SNPs) as proxies for a larger set of genetically redundant SNPs. A pilot genome-wide study in 180 AD-treated patients has been already performed in the Unit, aimed to identify genetic predictors of clinical response. 3) Statistical and bioinformatic analyses. Once genotypic data are generated in the wet laboratory work-flow, conventional (chi-square analysis; Fisher’s exact test) and non-conventional statistical tests and approaches (false-discovery rate estimation; permutation procedures; pathway analyses) need to be used to select and prioritize SNPs and CNVs associated with the trait of interest, whether disease occurrence, clinical response to treatment, or prognosis. The availability of genome-wide data typed with Illumina® on a large set of MS patients and controls as part of the IMSGC consortium will serve as database for the application of these approaches.Il contenuto va qui, fai clic sul pulsante modifica per modificare questo testo.
Gironi M*, Martinelli-Boneschi F*, Sacerdote P, Solaro C, Zaffaroni M, Cavarretta R, Moiola L, Bucello S, Radaelli M, Pilato V, Rodegher M, Cursi M, Franchi S, Martinelli V, Nemni R, Comi G*, Martino G*. A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis. Multiple Sclerosis. 2008;14(8):1076-83.
Martinelli Boneschi F, Aridon P, Zara F, Guerrini R, Comi G, Casari G. No evidence of ATP1A2 involvement in Twelve Multiplex Italian families with Benign Familial Infantile Seizures. Neuroscience letters 2005; 388(2):71-4.
Furlan R, Rovaris M, Martinelli Boneschi F, Bergami A, Gironi M, Deleidi M, Agosta F, Franciotta D, Scarpini E, Uccelli A, Zaffaroni M, Kurne A, Comi G, Olsson T, Filippi M, Martino G. Immunological patterns identifying disease course and evolution in multiple sclerosis patients. Journal of Neuroimmunology 2005; 165(1-2):192-200.
Del Bo R, Scarlato M, Ghezzi S, Martinelli Boneschi F, Fenoglio C, Galbiati S, Virgilio R, Galimberti D, Galimberti G, Crimi M, Ferrarese C, Scarpini E, Bresolin N, Comi GP. Vascular endothelial growth factor gene variability is associated with increased risk for AD. Annals of Neurology 2005;57(3):373-80.
Kalachikov S, Evgrafov O, Ross B, Winawer M, Barker-Cummings C, Martinelli Boneschi F, Choi C, Morozov P, Das K, Teplitskaya E, Yu A, Cayanis E, Penchaszadeh G, Kottmann AH, Pedley TA, Hauser WA, Ottman R, Gilliam TC. Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet. 2002;30(3):335-41Il contenuto va qui, fai clic sul pulsante modifica per modificare questo testo.