Several loci (PARK1 to 13) for familial Parkinson Disease (PD) have been described, but for some of them the specific gene remains elusive. GIGYF2 (Grb10-Interacting GYF Protein-2) has been recently proposed to be the causative gene at the PARK11 locus as a total of 10 different genetic variants were identified in this gene in 123 Italian and 126 French familial PD cases, being absent in 318 controls. Although GIGYF2 represents a good candidate gene for PD, being known to modulate the IGF-1 (insulin-like growth factor 1) signaling through its interaction with the Grb10 protein, further studies did not confirm its association with the disease. Therefore, to elucidate the role of GIGYF2 in the pathogenesis of familial and sporadic PD, we screened GIGYF2 in a large Italian population of familial and sporadic PD patients and controls. Moreover, we analyzed the function of GIGYF2 in vivo, using the zebrafish model. Mutational screening of GIGYF2 was performed by a combination of high-resolution melting analysis and direct DNA sequencing. Exons containing previously reported mutations were analyzed in 552 cases (243 familial, 309 sporadic) and 552 controls. Thereafter, a subset of 184 familial PD cases and an equal number of controls were subjected to a full screening of all 27 coding exons. This analysis identified 7 different missense variations in a total of 8 individuals (3 PD patients and 5 controls). Abrogation of gigyf2 function in zebrafish embryos by morpholino oligonucleotide injection did not lead to a drastic loss of neurons in the diencephalic dopaminergic (DA) neuron clusters, neither caused a change in the expression levels of otp1 and prox1 genes, two of the major players in diencephalic DA neurons development, suggesting that gigyf2 is not required for proper DA neuron differentiation. These data, together with those recently reported by other groups, suggest that GIGYF2 is unlikely to be the PARK11 gene.

Mutational screening and functional analyses in the zebrafish model of GIGYF2 as a candidate gene for Parkinson disease / I. Guella, L. Del Giacco, R. Asselta, A. Pistocchi, V. Rimoldi, F. Sironi, P. Primignani, M. Zini, G. Pezzoli, S. Duga, S. Goldwurm. ((Intervento presentato al 4. convegno Meeting on the molecular mechanisms of neurodegeneration tenutosi a Milano nel 2009.

Mutational screening and functional analyses in the zebrafish model of GIGYF2 as a candidate gene for Parkinson disease

I. Guella;L. Del Giacco;R. Asselta;A. Pistocchi;V. Rimoldi;S. Duga;
2009-05

Abstract

Several loci (PARK1 to 13) for familial Parkinson Disease (PD) have been described, but for some of them the specific gene remains elusive. GIGYF2 (Grb10-Interacting GYF Protein-2) has been recently proposed to be the causative gene at the PARK11 locus as a total of 10 different genetic variants were identified in this gene in 123 Italian and 126 French familial PD cases, being absent in 318 controls. Although GIGYF2 represents a good candidate gene for PD, being known to modulate the IGF-1 (insulin-like growth factor 1) signaling through its interaction with the Grb10 protein, further studies did not confirm its association with the disease. Therefore, to elucidate the role of GIGYF2 in the pathogenesis of familial and sporadic PD, we screened GIGYF2 in a large Italian population of familial and sporadic PD patients and controls. Moreover, we analyzed the function of GIGYF2 in vivo, using the zebrafish model. Mutational screening of GIGYF2 was performed by a combination of high-resolution melting analysis and direct DNA sequencing. Exons containing previously reported mutations were analyzed in 552 cases (243 familial, 309 sporadic) and 552 controls. Thereafter, a subset of 184 familial PD cases and an equal number of controls were subjected to a full screening of all 27 coding exons. This analysis identified 7 different missense variations in a total of 8 individuals (3 PD patients and 5 controls). Abrogation of gigyf2 function in zebrafish embryos by morpholino oligonucleotide injection did not lead to a drastic loss of neurons in the diencephalic dopaminergic (DA) neuron clusters, neither caused a change in the expression levels of otp1 and prox1 genes, two of the major players in diencephalic DA neurons development, suggesting that gigyf2 is not required for proper DA neuron differentiation. These data, together with those recently reported by other groups, suggest that GIGYF2 is unlikely to be the PARK11 gene.
Settore BIO/11 - Biologia Molecolare
Settore BIO/06 - Anatomia Comparata e Citologia
Mutational screening and functional analyses in the zebrafish model of GIGYF2 as a candidate gene for Parkinson disease / I. Guella, L. Del Giacco, R. Asselta, A. Pistocchi, V. Rimoldi, F. Sironi, P. Primignani, M. Zini, G. Pezzoli, S. Duga, S. Goldwurm. ((Intervento presentato al 4. convegno Meeting on the molecular mechanisms of neurodegeneration tenutosi a Milano nel 2009.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/57407
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