1) Genetic basis of episodic disorders: migraine and ataxia
Episodic neurological diseases, such as ataxia and migraine, fit well into the paradygm of common, complex diseases with rarer mendelian, monogenic forms. They have been classified as "channelopathies" on the basis of their molecular etiology. This term has been coined to designate those diseases caused by defects in ion channels, which include a wide variety of phenotypes, ranging from heart defects to diseases of the central nervous system (CNS). The identification of mutations in a subunit of one of these ion channels, CACNA1A, underlying migraine and ataxia in human and mouse, underscores the close relationship among these disorders at the molecular level. Our aim is to study the genetic basis of episodic neurological channelopathies, following positional cloning and candidate gene approaches in mendelian cases, and association studies in multifactorial forms. Functional studies of mutated ion channels are also being performed in cell lines.
Collaborators
Dr. José Manuel Fernández (Universitat Pompeu Fabra) Dr. Alfons Macaya (Hospital Universitari Vall d’Hebron)
Dr. Bernat Narberhaus (Hospital Sant Joan de Déu, Manresa) Dr. Miguel Valverde (Universitat Pompeu Fabra) Dr. Víctor Volpini (Institut de Recerca Oncològica, IRO)
2) Genetic predisposition to neuropsychiatric disorders: drug addictions and ADHD
Attention deficit hyperactivity disorder (ADHD) and drug addictions are highly prevalent neuropsychiatric disorders. Although environmental factors play an essential role in both disorders, there are strong evidences of a complex genetic contribution. Our research aims to evaluate the involvement of genes with a potential role in cocaine and heroin dependence, including those involved in physical and behavioural alterations, those related to comorbid personality and psychopathological traits and those encoding proteins involved in drug transport and metabolism. We also focus on genes potentially involved in the susceptibility to develop ADHD, selected on the basis of pharmacological, biochemical and neuropathological data, and animal models and linkage/association studies. The methodological approach is based on high throughput SNP genotyping with case-control and family-based designs, followed by functional analysis of those genetic variants showing significant association to the trait.
Collaborators Dr. Mònica Bayés (Centre de Regulació Genòmica, Barcelona) Dr. Xavier Estivill (Centre de Regulació Genòmica, Barcelona) Dr. Miquel Casas (Servei de Psiquiatria, Hospital Vall d’Hebron) Carlos Roncero (Servei de Psiquiatria, Hospital Vall d’Hebron) Dr. Rafael Artuch (Hospital Sant Joan de Déu, Barcelona)
Dr. Rafael Maldonado (Universitat Pompeu Fabra, Barcelona)
3) Genetic basis of lysosomal storage disorders: Maroteaux-Lamy syndrome
Mucopolysaccharidosis VI or Maroteaux-Lamy syndrome is a rare autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), a lysosomal enzyme involved in the degradation of dermatan sulphate and chondroitin sulphate. Intralysosomal accumulation of these glycosaminoglycans causes a progressive damage in skeletal and muscular tissues. Patients usually present dwarfism, dysostosis multiplex and diverse skeletal defects, aortic dysfunction, hepatoesplenomegaly and corneal clouding. Our research focuses on the identification of the molecular defects of the ARSB gene underlying the disease in patients from Spain and Argentina. Our aim is also to functionally characterize the mutant alleles at RNA and protein levels, by analyzing abnormal splicing, putative nonsense mediated RNA decay mechanisms, altered intracellular protein trafficking and defective enzymatic activity.
with rarer mendelian, monogenic forms. They have been classified as "channelopathies" on the basis of their molecular etiology. This term has been coined to designate those diseases caused by defects in ion channels, which include a wide variety of phenotypes, ranging from heart defects to diseases of the central nervous system (CNS). The identification of mutations in a subunit of one of these ion channels, CACNA1A, underlying migraine and ataxia in human and mouse, underscores the close relationship among these disorders at the molecular level. Our aim is to study the genetic basis of episodic neurological channelopathies, following positional cloning and candidate gene approaches in mendelian cases, and association studies in multifactorial forms. Functional studies of mutated ion channels are also being performed in cell lines.
Our research aims to evaluate the involvement of genes with a potential role in cocaine and heroin dependence, including those involved in physical and behavioural alterations, those related to comorbid personality and psychopathological traits and those encoding proteins involved in drug transport and metabolism. We also focus on genes potentially involved in the susceptibility to develop ADHD, selected on the basis of pharmacological, biochemical and neuropathological data, and animal models and linkage/association studies. The methodological approach is based on high throughput SNP genotyping with case-control and family-based designs, followed by functional analysis of those genetic variants showing significant association to the trait. 
Mucopolysaccharidosis VI or Maroteaux-Lamy syndrome is a rare autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), a lysosomal enzyme involved in the degradation of dermatan sulphate and chondroitin sulphate. Intralysosomal accumulation of these glycosaminoglycans causes a progressive damage in skeletal and muscular tissues. Patients usually present dwarfism, dysostosis multiplex and diverse skeletal defects, aortic dysfunction, hepatoesplenomegaly and corneal clouding. Our research focuses on the identification of the molecular defects of the ARSB gene underlying the disease in patients from Spain and Argentina. Our aim is also to functionally characterize the mutant alleles at RNA and protein levels, by analyzing abnormal splicing, putative nonsense mediated RNA decay mechanisms, altered intracellular protein trafficking and defective enzymatic activity.