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Auteur L. Alison MCINNES |
Documents disponibles écrits par cet auteur (2)
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Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions / Takeshi SAKURAI in Autism Research, 4-1 (February 2011)
[article]
Titre : Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions Type de document : Texte imprimé et/ou numérique Auteurs : Takeshi SAKURAI, Auteur ; Nathan P. DORR, Auteur ; Nagahide TAKAHASHI, Auteur ; L. Alison MCINNES, Auteur ; Gregory A. ELDER, Auteur ; Joseph D. BUXBAUM, Auteur Année de publication : 2011 Article en page(s) : p.28-39 Langues : Anglais (eng) Mots-clés : social behavior intellectual disability autism mouse model Index. décimale : PER Périodiques Résumé : Identifying genes involved in social behavior is important for autism research. Williams–Beuren syndrome (WBS) is a developmental syndrome with unique neurocognitive features, including low IQ, deficits in visuospatial and visual-motor abilities, hypersensitivity to sounds, hypersociability, and increased general anxiety. The syndrome is caused by a recurrent hemizygous deletion of the 7q11.23 region, containing about 28 genes. One of genes in the region, GTF2I, has been implicated in the hypersociability and visuospatial deficits of WBS based on genotype–phenotype correlation studies of patients with atypical deletions. In order to clarify the involvement of GTF2I in neurocognitive function, especially social behavior, we have developed and characterized Gtf2i-deficient mice. We found that homozygous deletion of Gtf2i causes lethality during embryonic development with neural tube closure defects and exencephaly, consistent with other reports. Gtf2i heterozygous animals show no gross changes in brain structure or development. Furthermore, heterozygous animals show no alterations in learning and memory, including spatial memory as assessed by the Morris water maze, but show alterations in the recognition of novel objects. Interestingly, they show increased social interaction with unfamiliar mice and do not show typical social habituation processes, reminiscent of the hypersociability observed in WBS patients. The mice do not appear to show increased anxiety, supporting a specific effect of Gtf2i on defined domains of the WBS phenotype. These data indicate that Gtf2i is involved in several aspects of embryonic development and the development of social neurocircuitry and that GTF2I haploinsufficiency could be a contributor to the hypersociability in WBS patients. En ligne : http://dx.doi.org/10.1002/aur.169 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118
in Autism Research > 4-1 (February 2011) . - p.28-39[article] Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions [Texte imprimé et/ou numérique] / Takeshi SAKURAI, Auteur ; Nathan P. DORR, Auteur ; Nagahide TAKAHASHI, Auteur ; L. Alison MCINNES, Auteur ; Gregory A. ELDER, Auteur ; Joseph D. BUXBAUM, Auteur . - 2011 . - p.28-39.
Langues : Anglais (eng)
in Autism Research > 4-1 (February 2011) . - p.28-39
Mots-clés : social behavior intellectual disability autism mouse model Index. décimale : PER Périodiques Résumé : Identifying genes involved in social behavior is important for autism research. Williams–Beuren syndrome (WBS) is a developmental syndrome with unique neurocognitive features, including low IQ, deficits in visuospatial and visual-motor abilities, hypersensitivity to sounds, hypersociability, and increased general anxiety. The syndrome is caused by a recurrent hemizygous deletion of the 7q11.23 region, containing about 28 genes. One of genes in the region, GTF2I, has been implicated in the hypersociability and visuospatial deficits of WBS based on genotype–phenotype correlation studies of patients with atypical deletions. In order to clarify the involvement of GTF2I in neurocognitive function, especially social behavior, we have developed and characterized Gtf2i-deficient mice. We found that homozygous deletion of Gtf2i causes lethality during embryonic development with neural tube closure defects and exencephaly, consistent with other reports. Gtf2i heterozygous animals show no gross changes in brain structure or development. Furthermore, heterozygous animals show no alterations in learning and memory, including spatial memory as assessed by the Morris water maze, but show alterations in the recognition of novel objects. Interestingly, they show increased social interaction with unfamiliar mice and do not show typical social habituation processes, reminiscent of the hypersociability observed in WBS patients. The mice do not appear to show increased anxiety, supporting a specific effect of Gtf2i on defined domains of the WBS phenotype. These data indicate that Gtf2i is involved in several aspects of embryonic development and the development of social neurocircuitry and that GTF2I haploinsufficiency could be a contributor to the hypersociability in WBS patients. En ligne : http://dx.doi.org/10.1002/aur.169 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region / L. Alison MCINNES in Molecular Autism, (March 2010)
[article]
Titre : A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region Type de document : Texte imprimé et/ou numérique Auteurs : L. Alison MCINNES, Auteur ; Catalina BETANCUR, Auteur ; Joseph GLESSNER, Auteur ; Lisa EDELMANN, Auteur ; Elina R. MANGHI, Auteur ; Marietha FALLAS, Auteur ; Patricia JIMENEZ GONZALEZ, Auteur ; Tracy BRANDT, Auteur ; Marion PILORGE, Auteur ; Alisa NAKAMINE, Auteur ; Joseph D. BUXBAUM, Auteur ; Hakon HAKONARSON, Auteur Année de publication : 2010 Article en page(s) : 12 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background
The 15q24 microdeletion syndrome has been recently described as a recurrent, submicroscopic genomic imbalance found in individuals with intellectual disability, typical facial appearance, hypotonia, and digital and genital abnormalities. Gene dosage abnormalities, including copy number variations (CNVs), have been identified in a significant fraction of individuals with autism spectrum disorders (ASDs). In this study we surveyed two ASD cohorts for 15q24 abnormalities to assess the frequency of genomic imbalances in this interval.
Methods
We screened 173 unrelated subjects with ASD from the Central Valley of Costa Rica and 1336 subjects with ASD from 785 independent families registered with the Autism Genetic Resource Exchange (AGRE) for CNVs across 15q24 using oligonucleotide arrays. Rearrangements were confirmed by array comparative genomic hybridization and quantitative PCR.
Results
Among the patients from Costa Rica, an atypical de novo deletion of 3.06 Mb in 15q23-q24.1 was detected in a boy with autism sharing many features with the other 13 subjects with the 15q24 microdeletion syndrome described to date. He exhibited intellectual disability, constant smiling, characteristic facial features (high anterior hairline, broad medial eyebrows, epicanthal folds, hypertelorism, full lower lip and protuberant, posteriorly rotated ears), single palmar crease, toe syndactyly and congenital nystagmus. The deletion breakpoints are atypical and lie outside previously characterized low copy repeats (69,838-72,897 Mb). Genotyping data revealed that the deletion had occurred in the paternal chromosome. Among the AGRE families, no large 15q24 deletions were observed.
Conclusions
From the current and previous studies, deletions in the 15q24 region represent rare causes of ASDs with an estimated frequency of 0.1 to 0.2% in individuals ascertained for ASDs, although the proportion might be higher in sporadic cases. These rates compare with a frequency of about 0.3% in patients ascertained for unexplained intellectual disability and congenital anomalies. This atypical deletion reduces the minimal interval for the syndrome from 1.75 Mb to 766 kb, implicating a reduced number of genes (15 versus 38). Sequencing of genes in the 15q24 interval in large ASD and intellectual disability samples may identify mutations of etiologic importance in the development of these disorders.En ligne : http://dx.doi.org/10.1186/2040-2392-1-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102
in Molecular Autism > (March 2010) . - 12 p.[article] A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region [Texte imprimé et/ou numérique] / L. Alison MCINNES, Auteur ; Catalina BETANCUR, Auteur ; Joseph GLESSNER, Auteur ; Lisa EDELMANN, Auteur ; Elina R. MANGHI, Auteur ; Marietha FALLAS, Auteur ; Patricia JIMENEZ GONZALEZ, Auteur ; Tracy BRANDT, Auteur ; Marion PILORGE, Auteur ; Alisa NAKAMINE, Auteur ; Joseph D. BUXBAUM, Auteur ; Hakon HAKONARSON, Auteur . - 2010 . - 12 p.
Langues : Anglais (eng)
in Molecular Autism > (March 2010) . - 12 p.
Index. décimale : PER Périodiques Résumé : Background
The 15q24 microdeletion syndrome has been recently described as a recurrent, submicroscopic genomic imbalance found in individuals with intellectual disability, typical facial appearance, hypotonia, and digital and genital abnormalities. Gene dosage abnormalities, including copy number variations (CNVs), have been identified in a significant fraction of individuals with autism spectrum disorders (ASDs). In this study we surveyed two ASD cohorts for 15q24 abnormalities to assess the frequency of genomic imbalances in this interval.
Methods
We screened 173 unrelated subjects with ASD from the Central Valley of Costa Rica and 1336 subjects with ASD from 785 independent families registered with the Autism Genetic Resource Exchange (AGRE) for CNVs across 15q24 using oligonucleotide arrays. Rearrangements were confirmed by array comparative genomic hybridization and quantitative PCR.
Results
Among the patients from Costa Rica, an atypical de novo deletion of 3.06 Mb in 15q23-q24.1 was detected in a boy with autism sharing many features with the other 13 subjects with the 15q24 microdeletion syndrome described to date. He exhibited intellectual disability, constant smiling, characteristic facial features (high anterior hairline, broad medial eyebrows, epicanthal folds, hypertelorism, full lower lip and protuberant, posteriorly rotated ears), single palmar crease, toe syndactyly and congenital nystagmus. The deletion breakpoints are atypical and lie outside previously characterized low copy repeats (69,838-72,897 Mb). Genotyping data revealed that the deletion had occurred in the paternal chromosome. Among the AGRE families, no large 15q24 deletions were observed.
Conclusions
From the current and previous studies, deletions in the 15q24 region represent rare causes of ASDs with an estimated frequency of 0.1 to 0.2% in individuals ascertained for ASDs, although the proportion might be higher in sporadic cases. These rates compare with a frequency of about 0.3% in patients ascertained for unexplained intellectual disability and congenital anomalies. This atypical deletion reduces the minimal interval for the syndrome from 1.75 Mb to 766 kb, implicating a reduced number of genes (15 versus 38). Sequencing of genes in the 15q24 interval in large ASD and intellectual disability samples may identify mutations of etiologic importance in the development of these disorders.En ligne : http://dx.doi.org/10.1186/2040-2392-1-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102