Study of copy number variants in autism spectrum disorders and their comorbidities
Autism Spectrum Disorders (ASDs) are a group of multifactorial, heterogeneous neurodevelopmental disorders characterized by deficits in communication and social interaction, and repetitive behaviors. The prevalence is ~1% worldwide with a 4:1 male to female ratio. Several co-morbidities have been associated with Autism Spectrum Disorders including intellectual disability, craniofacial malformations, head circumference defects (micro/macrocephaly), gastrointestinal problems, and heart malformations.
CNVs (e.g. deletion, duplication, insertion, inversion) represent the most frequent types of genetic lesion in both rare and common human genetic disorders. To date, close to 500 CNVs have been associated with ASD. The interpretation of these lesions is both acute and challenging. The primary focus in our laboratory is to understand how genetic variation can impact the development and homeostasis of the nervous system. To this goal, we have developed animal models and assays to study the impact of gene dosage defects on basic neurodevelopmental processes to:
- Discover genes and alleles that contribute to diseases
- Capture and validate genetic interactions (cis- and trans-modulators)
- Identify genes implicated in ASD-associated comorbidities
The laboratory employs an innovative orthogonal approach to tackle the current challenges in the field by combining in vivo modeling in the developing zebrafish and genomic tools. Ultimately, our work will contribute to the stratification of this highly heterogeneous group of disorders and will, in turn, inform diagnosis and patient care.
- Functional dissection of the 16p11.2 BP2-BP3 CNV in zebrafish and mice
- Study of the impact on brain development and function in Kctd13 knockout mice
- Functional dissection of the 4p16.1 CNV in a syndromic form of autism
- Determining the impact of gene dosage perturbation of CHD8, a ASD candidate, on the development of the peripheral nervous system
- Autism Genes And Susceptibility For Gastrointestinal Defects: Functional Studies Utilizing Zebrafish Embryo As An In Vivo Model
Erica Davis (CHDM, Duke University, USA)
Bertrand Isidor (CHU, Nantes, France)
Nicholas Katsanis (CHDM, Duke University, USA)
Jean Louis Mandel (IGBMC, Illkirch, France)
Amélie Piton (IGBMC, Illkirch, France)
Alexandre Reymond (CIG, Lausanne, Switzerland)
Raman Sharma (Robinson Reserch Institute, University of Adelaide, Australia)
Michael Talkowski (MGH, Broad Institute, Boston, USA)
Binnaz Yalcin (IGBMC, Illkirch, France)
- Christelle Golzio - ANR Jeunes chercheurs grant - - 2017
- Maria Nicla Loviglio - FRM “Post-doctorat en France” Fellowship - - 2017
- Camille Bonnet - Région Grand-Est PhD Fellowship - - 2017
- Christelle Golzio - LabEx INRT Starting package grant - 2016 - - 2016
- Maria Nicla Loviglio - SNSF Early Postdoc Mobility Fellowship 2016 - - 2016
Am J Med Genet A Jan 2020 ; 182:257-267 .
Eur J Hum Genet Feb. 17, 2020 .
Hum Mol Genet May 1, 2019 ; 28:1474-1486 .
Hum Mol Genet March 15, 2019 ; 28:912-927 .
Mol Psychiatry Feb 2018 ; Published online:1-22 .
Front Neurol Jan. 15, 2018 ; 8:747 .
Neuron Jan. 18, 2017 ; 93:331-347 .
Am J Hum Genet Oct. 5, 2017 ; 101:564-577 .
Hum Genomics July 19, 2017 ; 11:16 .
Am J Hum Genet April 6, 2017 ; 100:689 .