Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular basis of complex heritability in natural genotype-to-phenotype relationships

ABSTRACT: The intrinsic complexity of quantitative traits was evident even before the molecular nature of the gene was understood. Yet we still lack a detailed molecular understanding of complex heritability. Here we alleviated statistical roadblocks to high-resolution genetic mapping by using an inbred population of diploid yeast with very low linkage disequilibrium and more individuals than segregating polymorphisms. We mapped over 18,000 quantitative trait loci, resolving more than 3,300 to single nucleotides. This allowed us to explore the molecular origins of complexity, hybrid vigor, pleiotropy, and gene ´ environment interactions and to rigorously estimate the distribution of fitness effects of natural genetic variation. Our results describe a comprehensive, high-resolution genotype-to-phenotype map and define general principles underlying the complexity of heredity.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE123702 | GEO | 2018/12/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states

Project description:Single cell RNA-sequencing revealed extensive transcriptional cell state diversity in cancer, often observed independently from genetic heterogeneity, raising the central question of how malignant cell states are encoded epigenetically. To address this, we performed multi-omics single-cell profiling – integrating DNA methylation, transcriptome, and genotyping within the same cells – of diffuse gliomas, tumors characterized by defined transcriptional cell state diversity. Direct comparison of the epigenetic profiles of distinct cell states revealed key switches for state transitions recapitulating neurodevelopmental trajectories, and highlighted dysregulated epigenetic mechanisms underlying gliomagenesis. We further developed a quantitative framework to measure cell state heritability and transition dynamics based on high resolution lineage trees directly in human samples. We demonstrated heritability of malignant cell states, with key differences in hierarchal vs. plastic cell state architectures in IDH-mutant glioma vs. IDH-wildtype glioblastoma, respectively. This work provides a framework anchoring transcriptional cancer cell states in their epigenetic encoding, inheritance and transition dynamics.

2021-05-31 | GSE151506 | GEO

Saccharomyces cerevisiae

Project description:Antagonistic pleiotropy conceals molecular adaptations in changing environments

| PRJNA597653 | ENA

Hsp90 shapes adaptation by controlling the fitness consequences of regulatory variation

Project description:The essential stress-responsive chaperone Hsp90 impacts development and adaptation from microbes to humans. Yet despite evidence of its role in evolution, pathogenesis, and oncogenic transformation, the molecular mechanisms by which Hsp90 alters the consequences of mutations remain vigorously debated. Here we exploit the power of nucleotide-resolution genetic mapping in Saccharomyces cerevisiae to uncover more than 1,000 natural variant-to-phenotype associations governed by this molecular chaperone. Strikingly, Hsp90 more frequently modified the phenotypic effects of cis-regulatory variation than variants that altered protein sequence. Moreover, these interactions made the largest contribution to Hsp90-dependent heredity. Nearly all interacting variants—both regulatory and protein-coding—fell within clients of Hsp90 or targets of its direct binding partners. Hsp90 activity affected mutations in evolutionarily young genes, segmental deletions, and heterozygotes, highlighting its influence on variation central to evolutionary novelty. Reconciling the diverse epistatic effects of this chaperone, synthetic transcriptional regulation and reconstructions of natural alleles by genome editing revealed a central role for Hsp90 in regulating the fundamental relationship between activity and phenotype. Our findings establish that non-coding variation is a core driver of Hsp90’s influence on heredity, offering a mechanistic explanation for the chaperone’s strong effects on evolution and development across species.

2023-10-30 | GSE242925 | GEO

Heritability of alternative splicing in the human genome

Project description:Alternative pre-mRNA splicing increases proteomic diversity and provides a potential mechanism underlying both phenotypic diversity and susceptibility to genetic disorders in human populations. To investigate the variation in splicing among humans on a genomewide scale, we use a comprehensive exon-targeted microarray to examine alternative splicing in lymphoblasts derived from the CEPH HapMap population. We show the identification of transcripts containing annotated and novel sequence verified exon skipping, intron retention, and cryptic splice site usage that are specific between individuals. Using family-based linkage analysis, we demonstrate Mendelian inheritance and segregation of specific splice isoforms with regulatory haplotypes for three genes. Allelic association was further used to identify individual SNPs or regulatory haplotype blocks linked to the alternative splicing event, taking advantage of the high-resolution genotype information from the CEPH HapMap population. Keywords: Comparative genomic hybridiation within a 3 generation pedigree We used 14 individuals from the 3 generation CEPH/UTAH 1444 pedigree for our analysis of looking at heritability of differentially spliced exons within the family. 3 biological growths of individuals NA12739, NA12740, NA12750, and NA12751 were used and a single biological growth for the remaining 10 individuals.

2007-08-07 | E-GEOD-7952 | biostudies-arrayexpress

Functional Genomics of Human Skeletal Development and the Patterning of Height Heritability [RNA-Seq]

Project description:High-resolution profiling of epigenetic/transcriptomic behaviours of chondrocytes during skeletal development suggest the importance of generalized growth to adult height patterning

2024-11-15 | GSE252288 | GEO

Functional Genomics of Human Skeletal Development and the Patterning of Height Heritability [ATAC-Seq]

2024-11-15 | GSE252289 | GEO

Mus musculus

Project description:Reprogramming roadblocks are system-dependent

| PRJNA289631 | ENA

Heritability of alternative splicing in the human genome

2007-08-08 | GSE7952 | GEO

Trans regulatory evolution of a young microRNA during Drosophila spermatogenesis

Project description:Both cis and trans regulatory evolution underlies phenotypic innovation and diversification. However, how the nascent trans regulators escape negative pleiotropy, which may constrain their evolution and contribution to adaptation, remain unclear. Here, we compare the testis transcriptomes at single-cyst level between knockout lines of miRNA-983, an adaptively evolving young miRNA, in D. melanogaster and D. simulans, and the replacement line of dme-miR-983 with dsi-miR-983 in D. melanogaster. By distinguishing context effects and miR-983 effects in the framework of cis and trans regulation of gene expression, we demonstrate that miR-983 contributes to interspecific expression divergence in spite of its antagonism with context effects which is often predominant. Gain and loss of miR-983 effects involve distinct gene sets featured in different phases of spermatogenesis, which may help minimize pleiotropy. The magnitude of miR-983 effects is negatively associated with the variability of target gene expression dynamics during spermatogenesis. Moreover, knocking out dme-miR-983 in D. melanogaster affects sperm length and sperm competitive ability, which can be rescued partially by dsi-miR-983. Our results provide empirical evidence for the resolution of negative pleiotropy, and also have broad evolutionary implications for the biological function of trans regulators.

2022-07-13 | GSE190885 | GEO

Self-renewal and differentiation dynamics of native hematopoietic stem and progenitor cells at single-cell resolution

Project description:Hematopoiesis has a long track record of embracing single-cell functional and molecular profiling technologies. However, a single-cell resolution quantitative model of native hematopoiesis has never been reported. Here, we employ persistent labelling of stem cells combined with time-series single-cell RNA-Seq (scRNA-Seq) to build the first quantitative model of the native blood stem and progenitor dynamics in the mouse bone marrow at single-cell resolution. We capture compartment-wide flux and net proliferation rates in real-time, thus revealing the distinct ways in which different blood lineages maintain their cellular output. By exploring the molecular layers of scRNA-Seq, we pinpoint molecular changes associated with changes in cell behavior, such as increased differentiation or growth rates. Finally, unlike immunophenotyping data, our model can easily be integrated with external data. This enabled quantitative comparison between homeostatic and transplantation conditions which highlighted lineages and specific stages within them with up-regulated differentiation.

2023-06-20 | GSE207412 | GEO

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