Primate genome architecture linked with formation mechanisms and functional consequences of structural variation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA196636 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:While nucleotide-resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact on phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing we constructed fine-resolution, species-specific structural variation and segmental duplication maps for five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, comprising thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques. Non-allelic homologous recombination, linked with genomic architecture, primarily shaped the genomes of great apes resulting in different SV formation mechanism landscapes across species, with distinct functional consequences. Transcriptome analyses across nonhuman primates and humans revealed significant effects of species-specific gene duplications on gene expression, with these effects displaying remarkable diversity in direction and magnitude. Thirteen inter-species gene duplications coincided with the species-specific gain of expression in a new tissue, implicating these duplications in function acquisition. Agilent arrays were custom designed for probes to be relatively evenly spaced across the reference genomes of chimpanzee, orang-utan, and rhesus macaque. For each species 9 one million probe arrays were used to cover the autosomes and a single 400k probe array was used for the sex chromosomes.
2013-08-10 | E-GEOD-45741 | biostudies-arrayexpress
Project description:While nucleotide-resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact on phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing we constructed fine-resolution, species-specific structural variation and segmental duplication maps for five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, comprising thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques. Non-allelic homologous recombination, linked with genomic architecture, primarily shaped the genomes of great apes resulting in different SV formation mechanism landscapes across species, with distinct functional consequences. Transcriptome analyses across nonhuman primates and humans revealed significant effects of species-specific gene duplications on gene expression, with these effects displaying remarkable diversity in direction and magnitude. Thirteen inter-species gene duplications coincided with the species-specific gain of expression in a new tissue, implicating these duplications in function acquisition.
2013-08-10 | GSE45741 | GEO
Project description:Although nucleotide resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact of phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing, we constructed fine-resolution genomic structural variation maps in five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, which are comprised of thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques compared with great apes. By comparison, nonallelic homologous recombination is specifically active in the great apes, which is correlated with architectural differences between the genomes of great apes and macaque. Transcriptome analyses across nonhuman primates and humans revealed effects of species-specific whole-gene duplication on gene expression. We identified 13 gene duplications coinciding with the species-specific gain of tissue-specific gene expression in keeping with a role of gene duplication in the promotion of diversification and the acquisition of unique functions. Differences in the present day activity of SV formation mechanisms that our study revealed may contribute to ongoing diversification and adaptation of great ape and Old World monkey lineages.
| S-EPMC3785719 | biostudies-literature
Project description:Linked-Read Sequencing to Resolve Complex Structural Variants
| PRJNA516494 | ENA
Project description:Linked-Read Sequencing to Resolve Complex Structural Variants
| PRJNA516493 | ENA
Project description:Copy number variants (CNVs) influence the expression of genes that map not only within the rearrangement, but also to its flanks. To assess the possible mechanism(s) underlying this “neighboring effect”, we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. Using chromosome conformation capture (4C-seq), we observed that a set of genes flanking the Williams-Beuren Syndrome critical region (WBSCR) were often looping together, possibly forming an interacting cluster with each other and the WBSCR. Deletion of the WBSCR disrupts the expression of this group of flanking genes, as well as long-range interactions between them and the rearranged interval. We also pinpointed concomitant changes in histone modifications between samples.We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thereby possibly modulating expression globally and modifying the phenotype. For example, we determined that the chromatin conformation, histone marks and relative expression levels of the flanking AUTS2 gene, mutations of which are associated with autism and intellectual disabilities, are modified in cell lines from Williams-Beuren syndrome patients. Examination of 4C-seq interaction profile of seven different genes (of which three in duplicate) in 2 different cell lines.
2013-11-20 | E-GEOD-33867 | biostudies-arrayexpress
Project description:Copy number variants (CNVs) influence the expression of genes that map not only within the rearrangement, but also to its flanks. To assess the possible mechanism(s) underlying this “neighboring effect”, we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. Using chromosome conformation capture (4C-seq), we observed that a set of genes flanking the Williams-Beuren Syndrome critical region (WBSCR) were often looping together, possibly forming an interacting cluster with each other and the WBSCR. Deletion of the WBSCR disrupts the expression of this group of flanking genes, as well as long-range interactions between them and the rearranged interval. We also pinpointed concomitant changes in histone modifications between samples.We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thereby possibly modulating expression globally and modifying the phenotype. For example, we determined that the chromatin conformation, histone marks and relative expression levels of the flanking AUTS2 gene, mutations of which are associated with autism and intellectual disabilities, are modified in cell lines from Williams-Beuren syndrome patients.
2013-11-20 | GSE33867 | GEO
Project description:Structural variation has played an important role in the evolutionary restructuring of human and great ape genomes. We generated approximately 10-fold genomic sequence coverage from a western lowland gorilla and integrated these data into a physical and cytogenetic framework to develop a comprehensive view of structural variation. We discovered and validated over 7,665 structural changes within the gorilla lineage including sequence resolution of inversions, deletions, duplications and retrotranspositions. A comparison with human and other ape genomes shows that the gorilla genome has been subjected to the highest rate of segmental duplication. We show that both the gorilla and chimpanzee genomes have experienced independent yet parallel patterns of structural mutation that have not occurred in humans, including the formation of subtelomeric heterochromatic caps, the hyperexpansion of segmental duplications and bursts of retroviral integrations. Our analysis suggests that the chimpanzee and gorilla genomes are structurally more derived than either orangutan or human. all combinations of human, chimpanzee and gorilla are used in 2 different arrayCGH designs. First, a standard 2.1 was used to detected CNVs, and second, we used a custom designed arrayCGH to validate gorilla specific duplications and deletions
2011-05-01 | E-GEOD-27072 | biostudies-arrayexpress
Project description:Structural variation has played an important role in the evolutionary restructuring of human and great ape genomes. We generated approximately 10-fold genomic sequence coverage from a western lowland gorilla and integrated these data into a physical and cytogenetic framework to develop a comprehensive view of structural variation. We discovered and validated over 7,665 structural changes within the gorilla lineage including sequence resolution of inversions, deletions, duplications and retrotranspositions. A comparison with human and other ape genomes shows that the gorilla genome has been subjected to the highest rate of segmental duplication. We show that both the gorilla and chimpanzee genomes have experienced independent yet parallel patterns of structural mutation that have not occurred in humans, including the formation of subtelomeric heterochromatic caps, the hyperexpansion of segmental duplications and bursts of retroviral integrations. Our analysis suggests that the chimpanzee and gorilla genomes are structurally more derived than either orangutan or human.
2011-05-01 | GSE27072 | GEO
Project description:We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se.
2020-03-02 | GSE116057 | GEO