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.
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.
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.
Project description:Improving the fertility of sheep is an important goal in sheep breeding as it greatly increases the productivity. Dolang sheep is a typical representative breed of lamb in Xinjiang and is the main local sheep breed and meat source in the region. To explore the genes associated with the initiation of puberty in Dolang sheep, the hypothalamic tissues of Dolang sheep prepubertal, pubertal, and postpubertal periods were collected for RNA-seq analysis on the Illumina platform.
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.