Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
Project description:Genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the functional role of many of these SNPs is largely unknown and tissue-specific resources are lacking. Expression quantitative trait loci (eQTL) mapping identifies target genes of disease-associated SNPs. Here, we comprehensively map eQTLs in the human colon, assess their relevance for GWAS of colonic diseases and provide functional characterization.
Project description:The genomic distribution of trait-associated SNPs (TASs) discovered in genome-wide association studies (GWAS) can provide insight into the genetic architecture of complex traits and the design of future studies. Here we report on a maize GWAS that identified TASs underlying five quantitative traits measured across a large panel of samples and examine the characteristics of these TASs. A set of SNPs obtained via RNA sequencing (RNA-seq), most of which are located within annotated genes (~87%) were complemented with additional SNPs from the maize HapMap Project that contains approximately equal proportions of intragenic and intergenic SNPs. TASs were identified via a genome scan while controlling for polygenic background effects. The diverse functions of TAS-containing candidate genes indicate that complex genetic networks shape these traits. The vast majority of the TAS-containing candidate genes have dynamic expression levels among developmental stages. Overall, TASs explain 44~54% of the total phenotypic variation for these traits, with equal contributions from intra- and inter-genic TASs. Association of ligueless2 with upper leaf angle was implicated by two intragenic TASs; rough sheath1 was associated with leaf width by an upstream intergenic TAS; and Zea agamous5 was associated with days to silking by both intra- and inter-genic TASs. A large proportion (82%) of these TASs comes from noncoding regions, similar to findings from human diseases and traits. However, TASs were enriched in both intergenic (53%) and promoter 5kb (24%) regions, but under-represented in a set of nonsynonymous SNPs.
Project description:ATAC-seq was performed in HUDEP-2 cells grown in expansion phase medium following the OMNI-ATAC protocol (Corces MR, et al. Nat. Methods, 2017).