The Haplotype Reference Consortium
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001001710 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Rapid advances in high-throughput DNA sequencing technologies are accelerating the pace of research into personalized medicine. While methods for variant discovery and genotyping from whole genome sequencing (WGS) datasets have been well established, linking variants together into a single haplotype remains a challenge. An understanding of complete haplotypes of an individual will help clarify the consequences of inheriting multiple alleles in combination, identify novel disease associations, and augment studies of gene regulation. Although numerous methods have been developed to reconstruct haplotypes from WGS data, chromosome-span haplotypes at high resolution have been difficult to obtain. Here we present a novel method to accurately reconstruct chromosome-span haplotypes from proximity-ligation and DNA shotgun sequencing. We demonstrate the utility of this approach in producing high-resolution chromosome-span haplotype phasing in mouse and human. While proximity-ligation based methods were originally designed to investigate spatial organization of the genome, our results lend support for their use as a general tool for haplotyping in the future. Hi-C experiments in two replicates of Human GM12878 Lymphoblastoid cells and two replicates of F123 mouse ES cells (4 total samples)
2013-11-03 | E-GEOD-48592 | biostudies-arrayexpress
Project description:Rapid advances in high-throughput DNA sequencing technologies are accelerating the pace of research into personalized medicine. While methods for variant discovery and genotyping from whole genome sequencing (WGS) datasets have been well established, linking variants together into a single haplotype remains a challenge. An understanding of complete haplotypes of an individual will help clarify the consequences of inheriting multiple alleles in combination, identify novel disease associations, and augment studies of gene regulation. Although numerous methods have been developed to reconstruct haplotypes from WGS data, chromosome-span haplotypes at high resolution have been difficult to obtain. Here we present a novel method to accurately reconstruct chromosome-span haplotypes from proximity-ligation and DNA shotgun sequencing. We demonstrate the utility of this approach in producing high-resolution chromosome-span haplotype phasing in mouse and human. While proximity-ligation based methods were originally designed to investigate spatial organization of the genome, our results lend support for their use as a general tool for haplotyping in the future.
2013-11-03 | GSE48592 | GEO
Project description:Constructing high-quality haplotype-resolved genome assemblies has substantially improved the ability to detect and characterize genetic variants. A targeted approach providing readily access to the rich information from haplotype-resolved genome assemblies will be appealing to groups of basic researchers and medical scientists focused on specific genomic regions. Here, using the 4.5 megabase, notoriously difficult-to-assemble major histocompatibility complex (MHC) region as an example, we demonstrated an approach to construct haplotype-resolved assembly of the targeted genomic region with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assembly, our targeted approach achieved comparable completeness and accuracy with reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal MHC haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses of the MHC region. Given its highly efficient use of resources, our approach can greatly facilitate population genetic studies of targeted regions, and may pave a new way to elucidate the molecular mechanisms in disease etiology.
2022-11-15 | GSE192499 | GEO
Project description:Constructing high-quality haplotype-resolved genome assemblies has substantially improved the ability to detect and characterize genetic variants. A targeted approach providing readily access to the rich information from haplotype-resolved genome assemblies will be appealing to groups of basic researchers and medical scientists focused on specific genomic regions. Here, using the 4.5 megabase, notoriously difficult-to-assemble major histocompatibility complex (MHC) region as an example, we demonstrated an approach to construct haplotype-resolved assembly of the targeted genomic region with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assembly, our targeted approach achieved comparable completeness and accuracy with reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal MHC haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses of the MHC region. Given its highly efficient use of resources, our approach can greatly facilitate population genetic studies of targeted regions, and may pave a new way to elucidate the molecular mechanisms in disease etiology.
2022-11-15 | GSE192501 | GEO
Project description:To explore the effect of human MHC haplotype on gene expression phenotype across the MHC, we examine the MHC transcriptomic landscape at the haplotype-specific resolution for three prominent MHC haplotypes (A2-B46-DR9, A33-B58-DR3 and A1-B8-DR3) derived from the RNA-sequencing of MHC-homozygous B-LCLs. We demonstrate that MHC-wide gene expression pattern is dictated by the underlying MHC haplotype and identify 37 differentially expressed genes among the haplotypes.
2017-07-07 | GSE83403 | GEO
Project description:Rapid advances in biochemical technologies have enabled several strategies for typing candidate HLA alleles, but linking them into a single MHC haplotype structure remains challenging. Here we have developed a multi-loci haplotype phasing technique and demonstrate its utility towards phasing of MHC and KIR loci in human samples. We accurately (~99%) reconstruct the complete haplotypes for over 90% of sequence variants spanning the 4-megabase region of these two loci. By haplotyping a majority of coding and non-coding alleles at the MHC and KIR loci in a single assay, this method has the potential to assist transplantation matching and facilitate investigation of the genetic basis of human immunity and disease. Complete haplotype phasing of 2 loci (MHC and KIR) in 1 human cell line.
2016-02-01 | E-GEOD-65726 | biostudies-arrayexpress
Project description:Rapid advances in biochemical technologies have enabled several strategies for typing candidate HLA alleles, but linking them into a single MHC haplotype structure remains challenging. Here we have developed a multi-loci haplotype phasing technique and demonstrate its utility towards phasing of MHC and KIR loci in human samples. We accurately (~99%) reconstruct the complete haplotypes for over 90% of sequence variants spanning the 4-megabase region of these two loci. By haplotyping a majority of coding and non-coding alleles at the MHC and KIR loci in a single assay, this method has the potential to assist transplantation matching and facilitate investigation of the genetic basis of human immunity and disease.
2016-02-01 | GSE65726 | GEO
Project description:The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a type of complex genomic rearrangement (CGR). Although it has been identified as an important mutation signature of pathogenicity for genomic disorders and cancer genomes, its architecture remains unresolved. Here we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping and StrandSeq the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ~2.2-5.5 kb of 100% nucleotide similarity. These data provide experimental evidence supporting the hypothesis that inverted LCRs act as a recombinant substrate. This type of CGR can result in multiple conformers which contributes to generate diverse SV haplotypes in susceptible loci.
2023-12-18 | GSE250451 | GEO
Project description:Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis and public release of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with geographic distance from Africa, as expected under a serial founder effect for an out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected—including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas—the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations. Keywords: High Density SNP array
2008-02-05 | GSE10331 | GEO
Project description:The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work. Gene expression data was determined of peripheral blood samples (n=705) from InChianti cohort.
2013-06-21 | E-GEOD-48152 | biostudies-arrayexpress