Xp11.2 Duplication in Females: Unique Features of a Rare Copy Number Variation.
Ontology highlight
ABSTRACT:
SUBMITTER: Czako M
PROVIDER: S-EPMC8080037 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Detailed analyses of the clone-based genome assembly reveal that the recent duplication content of mouse (4.94%) is now comparable to that of human (5.5%), in contrast to previous estimates from the whole-genome shotgun sequence assembly. However, the architecture of mouse and human genomes differs markedly: most mouse duplications are organized into discrete clusters of tandem duplications that show depletion of genes and transcripts and enrichment of long interspersed nuclear element (LINE) and long terminal repeat (LTR) retroposons. We assessed copy number variation of the C57BL/6J duplicated regions within 15 mouse strains previously used for genetic association studies, sequencing and the Mouse Phenome Project. We determined that over 60% of these base pairs are polymorphic among the strains (on average, there was 20 Mb of copy-number-variable DNA between different mouse strains). Our data suggest that different mouse strains show comparable, if not greater, copy number polymorphism when compared to human; however, such variation is more locally restricted. We show large and complex patterns of interstrain copy number variation restricted to large gene families associated with spermatogenesis, pregnancy, viviparity, pheromone signaling and immune response.
| S-EPMC2574762 | biostudies-literature
Project description:Detailed analyses of the clone-based genome assembly reveal that the recent duplication content of mouse (4.94%) is now comparable to that of human (5.5%), in contrast to previous estimates from the whole-genome shotgun sequence assembly. The architecture of mouse and human genomes differ dramatically; most mouse duplications are organized into discrete clusters of tandem duplications that are depleted for genes/transcripts and enriched for LINE1 and LTR retroposons. We assessed copy-number variation of the C57BL/6J duplicated regions within 15 mouse strains used for genetic association studies, sequencing, and the mouse phenome project. We determined that over 60% of these basepairs are polymorphic between the strains (on average 20 Mbp of copy-number variable DNA between different mouse strains). Our data suggest that different mouse strains show comparable, if not greater, copy-number polymorphism when compared to human; however, such variation is more locally restricted. We show large and complex patterns of inter-strain copy-number variation restricted to large gene families associated with spermatogenesis, pregnancy, viviparity, phermone signaling, and immune response. Keywords: comparative genomic hybridization
2008-05-10 | GSE11369 | GEO
Project description:Recent studies have established the role of rare copy number variants (CNVs) in several neurological disorders but the contribution of rare CNVs to cerebral palsy (CP) is not known. Fifty Caucasian families having children with CP were studied using two microarray designs. Potentially pathogenic, rare (<1% population frequency) CNVs were identified, and their frequency determined, by comparing the CNVs found in cases with 8329 adult controls with no known neurological disorders. Ten of the 50 cases (20%) had rare CNVs of potential relevance to CP; there were a total of 14 CNVs, which were observed in <0.1% (<8/8329) of the control population. Eight inherited from an unaffected mother: a 751-kb deletion including FSCB, a 1.5-Mb duplication of 7q21.13, a 534-kb duplication of 15q11.2, a 446-kb duplication including CTNND2, a 219-kb duplication including MCPH1, a 169-kb duplication of 22q13.33, a 64-kb duplication of MC2R, and a 135-bp exonic deletion of SLC06A1. Three inherited from an unaffected father: a 386-kb deletion of 12p12.2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25.3, and a 265-kb duplication of DAAM1. This is the first systematic study of CNVs in CP, and although it did not identify de novo mutations, has shown inherited, rare CNVs involving potentially pathogenic genes and pathways requiring further investigation.
| S-EPMC3865415 | biostudies-literature
Project description:Detailed analyses of the clone-based genome assembly reveal that the recent duplication content of mouse (4.94%) is now comparable to that of human (5.5%), in contrast to previous estimates from the whole-genome shotgun sequence assembly. The architecture of mouse and human genomes differ dramatically; most mouse duplications are organized into discrete clusters of tandem duplications that are depleted for genes/transcripts and enriched for LINE1 and LTR retroposons. We assessed copy-number variation of the C57BL/6J duplicated regions within 15 mouse strains used for genetic association studies, sequencing, and the mouse phenome project. We determined that over 60% of these basepairs are polymorphic between the strains (on average 20 Mbp of copy-number variable DNA between different mouse strains). Our data suggest that different mouse strains show comparable, if not greater, copy-number polymorphism when compared to human; however, such variation is more locally restricted. We show large and complex patterns of inter-strain copy-number variation restricted to large gene families associated with spermatogenesis, pregnancy, viviparity, phermone signaling, and immune response. Keywords: comparative genomic hybridization Genomic DNA of 14 inbred mouse strains was tested against reference C57BL/6J sample. C57BL/6J DNA sample from another individual was tested as negative control.
2008-05-10 | E-GEOD-11369 | biostudies-arrayexpress
Project description:OBJECTIVE:To identify shared genes and pathways between common absence epilepsy (AE) subtypes (childhood absence epilepsy [CAE], juvenile absence epilepsy [JAE], and unclassified absence epilepsy [UAE]) that may indicate common mechanisms for absence seizure generation and potentially a diagnostic continuum. METHODS:We used high-density single-nucleotide polymorphism arrays to analyze genome-wide rare copy number variation (CNV) in a cohort of 144 children with AEs (95 CAE, 26 UAE, and 23 JAE). RESULTS:We identified CNVs that are known risk factors for AE in 4 patients, including 3x 15q11.2 deletion. We also expanded the phenotype at 4 regions more commonly identified in other neurodevelopmental disorders: 1p36.33 duplication, 1q21.1 deletion, 22q11.2 duplication, and Xp22.31 deletion and duplication. Fifteen patients (10.5%) were found to carry rare CNVs that disrupt genes associated with neuronal development and function (8 CAE, 2 JAE, and 5 UAE). Four categories of protein are each disrupted by several CNVs: (1) synaptic vesicle membrane or vesicle endocytosis, (2) synaptic cell adhesion, (3) synapse organization and motility via actin, and (4) gap junctions. CNVs within these categories are shared across the AE subtypes. CONCLUSIONS:Our results have reinforced the complex and heterogeneous nature of the AEs and their potential for shared genetic mechanisms and have highlighted several pathways that may be important in epileptogenesis of absence seizures.
| S-EPMC4830185 | biostudies-literature
Project description:The Illumina Human Omni2.5 array is a high resolution microarray platform for studying copy number variations in the human genome. It is widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed this platform to investigate the risk factor CNVs in 281 individuals diagnosed with Antisocial Personality Disorder.
2021-06-01 | GSE116022 | GEO
Project description:Little is known about genes that underlie isolated single-suture craniosynostosis. In this study, we hypothesize that rare copy number variants (CNV) in patients with isolated single-suture craniosynostosis contain genes important for cranial development. Using whole genome array comparative genomic hybridization (CGH), we evaluated DNA from 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications. We identified a 1.1 Mb duplication encompassing RUNX2 in two affected cousins with metopic synostosis and hypodontia. Given that RUNX2 is required as a master switch for osteoblast differentiation and interacts with TWIST1, mutations in which also cause craniosynostosis, we conclude that the duplication in this family is pathogenic, albeit with reduced penetrance. In addition, we find that a total of 7.5% of individuals with single-suture synostosis in our series have at least one rare deletion or duplication that contains genes and that has not been previously reported in unaffected individuals. The genes within and disrupted by CNVs in this cohort are potential novel candidate genes for craniosynostosis.
| S-EPMC3104131 | biostudies-literature
Project description:While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD).We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial.CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100-200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction.Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects.
| S-EPMC4104153 | biostudies-literature
Project description:Although heritable factors are an important determinant of risk of early-onset cancer, the majority of these malignancies appear to occur sporadically without identifiable risk factors. Germline de novo copy-number variations (CNVs) have been observed in sporadic neurocognitive and cardiovascular disorders. We explored this mechanism in 382 genomes of 116 early-onset cancer case-parent trios and unaffected siblings. Unique de novo germline CNVs were not observed in 107 breast or colon cancer trios or controls but were indeed found in 7% of 43 testicular germ cell tumor trios; this percentage exceeds background CNV rates and suggests a rare de novo genetic paradigm for susceptibility to some human malignancies.
| S-EPMC3415553 | biostudies-literature
Project description:Neurodevelopmental problems (NPs) are more common in males, whereas anxiety and depression are more common in females. Rare copy number variants (CNVs) have been implicated in neurodevelopmental disorders. The aim of this study was to characterize the relationship between rare CNVs with NPs, anxiety, and depression in a childhood population sample, as well as to examine sex-specific effects. We analyzed a sample of N?=?12,982 children, of whom 5.3% had narrowly defined NPs (clinically diagnosed), 20.9% had broadly defined NPs (based on validated screening measures, but no diagnosis), and 3.0% had clinically diagnosed anxiety or depression. Rare (<1% frequency) CNVs were categorized by size (100-500?kb or?>?500?kb), type, and putative relevance to NPs. We tested for association of CNV categories with outcomes and examined sex-specific effects. Medium deletions (OR[CI]?=?1.18[1.05-1.33], p?=?.0053) and large duplications (OR[CI]?=?1.45[1.19-1.75], p?=?.00017) were associated with broadly defined NPs. Large deletions (OR[CI]?=?1.85[1.14-3.01], p?=?.013) were associated with narrowly defined NPs. There were no significant sex differences in CNV burden in individuals with NPs. Although CNVs were not associated with anxiety/depression in the whole sample, in individuals diagnosed with these disorders, females were more likely to have large CNVs (OR[CI]?=?3.75[1.45-9.68], p?=?.0064). Rare CNVs are associated with both narrowly and broadly defined NPs in a general population sample of children. Our results also suggest that large, rare CNVs may show sex-specific phenotypic effects.
| S-EPMC6767107 | biostudies-literature