Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1198679 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: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:Reading between the lines: molecular characterization of five widely used canine lymphoid tumor cell lines
| PRJNA339402 | ENA
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:The human MHC is a paradigm for genomics, showing striking association with disease but functional variants remain largely unresolved. Using an original hybrid microarray (containing tiling and junction probes) for the MHC and accounting for known sequence diversity, we have drawn the first high-resolution, strand-specific transcriptional map of the MHC, defining differences in gene expression for three common haplotypes associated with autoimmune disease. In total, 6% of the MHC is transcribed with one transcript per 1.4kb, including previously unrecognized intergenic transcription. The distributions of differentially expressed probes and polymorphisms between haplotypes are significantly correlated, arguing for cis effects. Haplotype-specific transcription involved 96 differentially expressed genes, including ZFP57, which was validated in a cohort of healthy volunteers, while 526 exons show haplotypic differences. We also find splicing events are significantly more extensive in the MHC than in the rest of the genome. This study marks a new step in immunogenetics. The results files (.wig and .gff) contain tiling data for both the shared-path and the alternate paths (shared and haplotype-specific) , defining transcriptional activity across the entire MHC region in each sample. Lymphoblastoid cell lines carrying three common autoimmunity haplotypes (COX, PGF, QBL) were analysed in triplicate using the custom MHC array, under both unstimulated and stimulated (200nM PMA and 125nM ionomycin for 6 hours) conditions.
2011-05-23 | E-GEOD-22453 | biostudies-arrayexpress
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.
2016-02-01 | GSE65726 | GEO
Project description:This experiment accompanies the main analysis using a custom MHC array to define the first high-resolution, strand-specific transcriptional map of the MHC, defining differences in gene expression for three common haplotypes associated with autoimmune disease. Unstimulated samples for each haplotype were hybridised to Affymetrix Human Exon 1.0 ST arrays as well the custom MHC array. Exon array data were used to assess the concordance of signal obtained from the two platforms and to investigate the extent of alternative splicing in the MHC, and how it compares to the rest of the genome. Lymphoblastoid cell lines carrying three common autoimmunity haplotypes (COX, PGF, QBL) were analysed in triplicate using the Affymetrix Human Exon 1.0 ST Array.
2011-05-23 | E-GEOD-22454 | biostudies-arrayexpress
Project description:The MHC region encodes HLA genes and is the most complex region in the human genome. The extensive polymorphic nature of the HLA hinders accurate localization and functional assessment of disease risk loci within this region. Using targeted capture sequencing and constructing individualized genomes for transcriptome alignment, we identified 908 novel transcripts within the human MHC region. These include 593 novel isoforms of known genes, 137 antisense strand RNAs, 119 novel long intergenic noncoding RNAs, and 5 transcripts of 3 novel putative protein-coding human endogenous retrovirus genes. We revealed allele-dependent expression imbalance involving 88% of all heterozygous transcribed single nucleotide polymorphisms throughout the MHC transcriptome. Among these variants, we show that the genetic variant associated with Behc ̧et’s disease in the HLA-B/MICA region, which tags HLA-B*51, is within novel long intergenic noncoding RNA transcripts that are exclusively expressed from the haplotype with the protective but not the disease risk allele. Further, we showed that the transcriptome within the MHC region can be defined by 14 distinct coexpression clusters, with evidence of coregulation by unique transcription factors in at least 9 of these clusters. Our data suggest a very complex regulatory map of the human MHC, and can help uncover functional consequences of disease risk loci in this region.
2018-05-02 | GSE108663 | GEO
Project description:The human MHC is a paradigm for genomics, showing striking association with disease but functional variants remain largely unresolved. Using an original hybrid microarray (containing tiling and junction probes) for the MHC and accounting for known sequence diversity, we have drawn the first high-resolution, strand-specific transcriptional map of the MHC, defining differences in gene expression for three common haplotypes associated with autoimmune disease. In total, 6% of the MHC is transcribed with one transcript per 1.4kb, including previously unrecognized intergenic transcription. The distributions of differentially expressed probes and polymorphisms between haplotypes are significantly correlated, arguing for cis effects. Haplotype-specific transcription involved 96 differentially expressed genes, including ZFP57, which was validated in a cohort of healthy volunteers, while 526 exons show haplotypic differences. We also find splicing events are significantly more extensive in the MHC than in the rest of the genome. This study marks a new step in immunogenetics. The results files (.bedgraph and .gff) contain tiling data for both the shared-path and the alternate paths (shared and haplotype-specific) , defining transcriptional activity across the entire MHC region in each sample.
2011-05-23 | GSE22453 | GEO