Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hidden genetic variation shapes the structure of functional elements in Drosophila.

ABSTRACT: Mutations that add, subtract, rearrange, or otherwise refashion genome structure often affect phenotypes, although the fragmented nature of most contemporary assemblies obscures them. To discover such mutations, we assembled the first new reference-quality genome of Drosophila melanogaster since its initial sequencing. By comparing this new genome to the existing D. melanogaster assembly, we created a structural variant map of unprecedented resolution and identified extensive genetic variation that has remained hidden until now. Many of these variants constitute candidates underlying phenotypic variation, including tandem duplications and a transposable element insertion that amplifies the expression of detoxification-related genes associated with nicotine resistance. The abundance of important genetic variation that still evades discovery highlights how crucial high-quality reference genomes are to deciphering phenotypes.

SUBMITTER: Chakraborty M

PROVIDER: S-EPMC5742068 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Hidden genetic variation shapes the structure of functional elements in Drosophila.

Chakraborty Mahul M VanKuren Nicholas W NW Zhao Roy R Zhang Xinwen X Kalsow Shannon S Emerson J J JJ

Nature genetics 20171218 1

Mutations that add, subtract, rearrange, or otherwise refashion genome structure often affect phenotypes, although the fragmented nature of most contemporary assemblies obscures them. To discover such mutations, we assembled the first new reference-quality genome of Drosophila melanogaster since its initial sequencing. By comparing this new genome to the existing D. melanogaster assembly, we created a structural variant map of unprecedented resolution and identified extensive genetic variation t ...[more]

PMID: 29255259

Similar Datasets

A common set of DNA regulatory elements shapes Drosophila appendages.

Project description:Animals have body parts made of similar cell types located at different axial positions, such as limbs. The identity and distinct morphology of each structure is often specified by the activity of different "master regulator" transcription factors. Although similarities in gene expression have been observed between body parts made of similar cell types, how regulatory information in the genome is differentially utilized to create morphologically diverse structures in development is not known. Here, we use genome-wide open chromatin profiling to show that among the Drosophila appendages, the same DNA regulatory modules are accessible throughout the genome at a given stage of development, except at the loci encoding the master regulators themselves. In addition, open chromatin profiles change over developmental time, and these changes are coordinated between different appendages. We propose that master regulators create morphologically distinct structures by differentially influencing the function of the same set of DNA regulatory modules.

| S-EPMC3866527 | biostudies-literature

Population structure shapes copy number variation in malaria parasites

Project description:If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in 7 countries in Africa, SE Asia and S. America using a high density SNP/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500bp to 59kb, as well as 10,107 flanking, biallelic SNPs. Overall, CNVs were rare, small and skewed towards low frequency variants, consistent with the deleterious model. Relative to African and SE Asian populations, CNVs were significantly more common in S. America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g. DNA helicase, and 3 conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen. SNP/CGH hybridisation of 175 malaria parasite samples

2015-11-19 | E-GEOD-75137 | biostudies-arrayexpress

A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci.

Project description:Genome-wide association studies (GWAS) have been highly informative in discovering disease-associated loci but are not designed to capture all structural variations in the human genome. Using long-read sequencing data, we discovered widespread structural variation within SINE-VNTR-Alu (SVA) elements, a class of great ape-specific transposable elements with gene-regulatory roles, which represents a major source of structural variability in the human population. We highlight the presence of structurally variable SVAs (SV-SVAs) in neurological disease-associated loci, and we further associate SV-SVAs to disease-associated SNPs and differential gene expression using luciferase assays and expression quantitative trait loci data. Finally, we genetically deleted SV-SVAs in the BIN1 and CD2AP Alzheimer's disease-associated risk loci and in the BCKDK Parkinson's disease-associated risk locus and assessed multiple aspects of their gene-regulatory influence in a human neuronal context. Together, this study reveals a novel layer of genetic variation in transposable elements that may contribute to identification of the structural variants that are the actual drivers of disease associations of GWAS loci.

| S-EPMC8997352 | biostudies-literature

A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci

Project description:Genome-wide association studies (GWAS) have been highly informative in discovering disease-associated loci, but are not designed to capture all structural variations in the human genome. Using long-read sequencing data, we discovered widespread structural variation within SVA (Sine-VNTR-Alu) elements, a class of great-ape specific transposable elements with gene-regulatory roles, which represents a major source of structural variability in the human population. We highlight the presence of structurally variable SVAs (SV-SVAs) in neurological disease-associated loci, and further associate SV-SVAs to disease-associated SNPs and differential gene expression using luciferase assays and expression quantitative trait loci data. Finally, we genetically deleted SV-SVAs in the BIN1 and CD2AP Alzheimer-associated risk loci and in the BCKDK Parkinson disease-associated risk locus and assessed multiple aspects of their gene-regulatory influence in a human neuronal context. Together, this study reveals a novel layer of genetic variation in transposable elements that may contribute to identification of the structural variants that are the actual drivers of disease-associations of GWAS loci.

2022-01-17 | GSE167409 | GEO

HSP90 Shapes the Consequences of Human Genetic Variation.

Project description:HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases.

| S-EPMC5325763 | biostudies-literature

Population structure shapes copy number variation in malaria parasites

2015-11-19 | GSE75137 | GEO

Mitochondrial polymorphism shapes intrapopulation behavioural variation in wild <i>Drosophila</i>.

Project description:Intrapopulation variation in behaviour, including activity, boldness and aggressiveness, is becoming more widely recognized and is hypothesized to substantially affect ecological and evolutionary dynamics. Although previous studies used candidate-gene approaches and genome-wide association analyses to identify genes correlated with variations in activity and aggressiveness, behavioural variation may not be fully captured in the nuclear genome, as it does not account for mitochondrial genomes. Mitochondrial genes encode products that are key regulators of the cellular energy-producing pathways in metabolic processes and are thought to play a significant role in life-history and reproductive traits. In this study, we considered many isofemale lines of Drosophila immigrans established from two wild populations to investigate whether intrapopulation variation in the mitochondrial genome affected activity level within this species. We identified two major haplogroups in these populations, and activity levels in both larvae and adults differed significantly between the two haplogroups. This result indicated that intrapopulation variation in activity level may be partially controlled by mitochondrial genes, along with the interaction between nuclear and mitochondrial genes and the age of individual organisms.

| S-EPMC8315832 | biostudies-literature

Population Structure Shapes Copy Number Variation in Malaria Parasites.

Project description:If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen.

| S-EPMC4760083 | biostudies-literature

A common set of DNA regulatory elements shapes Drosophila appendages

Project description:We mapped open chromatin by FAIRE-seq and measured gene expression by RNA-seq in 3 types of Drosophila samples: staged whole embryos, imaginal discs, pharate appendages. We first demonstrate that regions of open chromatin precisely define regions of enhancer activity in developing embryos. In contrast to the dynamic changes in open chromatin observed between different stages of embryogenesis, we found that the open chromatin profiles in wing, leg, and haltere imaginal discs are nearly identical. This was also true again later in development, where the adult appendages also share nearly identical open chromatin profiles. Therefore, at a given developmental time point, different appendages are specified using a shared set of DNA regulatory elements. However, from one time point to the next, the set of accessible regulatory elements changes. Open chromatin profiles in appendage imaginal discs are almost entirely different than those of the adult appendages. We propose that master regulator transcription factors create morphologically distinct structures by differentially influencing the function of the same set of DNA regulatory modules. Open chromatin profiling during Drosophila development: 3 stages of embryogenesis (2-replicates each); wing, leg, and haltere 3rd instar imaginal discs (3-replicates each); 3rd larval central nervous system (2-replicates); eye-antennal imaginal discs (2-replicates); wing, leg, and haltere pharate appendages (2-replicates each); Genomic DNA Inputs. Sequencing performed on Illumina GAII and HiSeq.

2013-11-07 | E-GEOD-38727 | biostudies-arrayexpress

Parental care shapes the evolution of molecular genetic variation.

Project description:Cooperative social behaviors, such as parental care, have long been hypothesized to relax selection leading to the accumulation of genetic variation in populations. Although the idea has been discussed for decades, there has been relatively little experimental work to investigate how social behavior contributes to genetic variation in populations. Here, we investigate how parental care can shape molecular genetic variation in the subsocial insect, Nicrophorus vespilloides. Using whole-genome sequencing of populations that had evolved in the presence or absence of parental care for 30 generations, we show that parental care maintains levels of standing genetic variation. In contrast, under a harsh environment without care, strong directional selection caused a reduction in genetic variation. Furthermore, we show that adaptation to the loss of care is associated with genetic divergence between populations at loci related to stress, morphological development, and transcriptional regulation. These data reveal how social behavior is linked to the genetic processes that shape and maintain genetic diversity within populations, and provides rare empirical evidence for an old hypothesis.

| S-EPMC10693002 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data