| 1. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 2. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 3. |
- Leblond, Claire S, et al.
(författare)
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Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n=396 patients and n=659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P=0.004, OR=2.37, 95% CI=1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P=0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.
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| 4. |
- Sequeira, Ana F., et al.
(författare)
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Cross-Eyed : Cross-Spectral Iris/Periocular Recognition Database and Competition
- 2016
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Ingår i: Proceedings of the 15th International Conference of the Biometrics Special Interest Group. - Piscataway, N.J. : IEEE. - 9783885796541 - 9781509007806
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Konferensbidrag (refereegranskat)abstract
- This work presents a novel dual-spectrum database containing both iris and periocular images synchronously captured from a distance and within a realistic indoor environment. This database was used in the 1st Cross-Spectrum Iris/Periocular Recognition Competition (Cross-Eyed 2016). This competition aimed at recording recent advances in cross- spectrum iris and periocular recognition. Six submissions were evaluated for cross-spectrum periocular recognition, and three for iris recognition. The submitted algorithms are briefly introduced. Detailed results are reported in this paper, and comparison of the results is discussed.
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| 5. |
- Sequeira, Ana F., et al.
(författare)
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Cross-Eyed 2017 : Cross-Spectral Iris/Periocular Recognition Competition
- 2017
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Konferensbidrag (refereegranskat)abstract
- This work presents the 2nd Cross-Spectrum Iris/Periocular Recognition Competition (Cross-Eyed2017). The main goal of the competition is to promote and evaluate advances in cross-spectrum iris and periocular recognition. This second edition registered an increase in the participation numbers ranging from academia to industry: five teams submitted twelve methods for the periocular task and five for the iris task. The benchmark dataset is an enlarged version of the dual-spectrum database containing both iris and periocular images synchronously captured from a distance and within a realistic indoor environment. The evaluation was performed on an undisclosed test-set. Methodology, tested algorithms, and obtained results are reported in this paper identifying the remaining challenges in path forward. © 2017 IEEE
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