The “MuTHER” (“Multiple Tissue Human Expression Resource”) project is undertaking a coordinated program of analysis designed to understand the relationships between genome sequence variation, methylation status, mRNA expression and disease phenotypes. The project aims to develop a resource of detailed genetic (genome-wide association; resequence) and genomic (expression; methylation) data from a range of tissues collected from a set of ~850 UK twins, as to support efforts to understand mechanisms involved in common trait susceptibility.
The specific aims of the MuTHER consortium are to:
- Investigate the genetic control of gene expression across multiple tissues in terms of heritability and cis and trans regulation.
- Investigate the relationship between genotype, gene expression and complex traits focusing primarily on traits that are tissue-appropriate or are in the established interests of the principal investigators.
- Assess the contribution of methylation to variation in gene expression and complex traits and any interaction with genetic effects.
- Relate gene expression networks to regulatory mechanisms and phenotypes.
- Explore the contribution of environmental factors to variation in gene expression and methylation.
The MuTHER project was established by the Wellcome Trust in 2007. Lymphocytes (LCLs and in some, fresh lymphocytes); subcutaneous fat; muscle and skin biopsies have been obtained from ~856 twins (1/3 monozygotic, 2/3 dizygotic) from the well-characterised TwinsUK BioResource (link to TwinsUK). All samples have been genome-wide expression profiled (Illumina HT-12v3 Chip) and genome-wide association data (Illumina 610k or 1M chip) and methylation data (27k Illumina array in first instance) will also be available shortly.