Scrutinizing the FTO locus: compelling evidence for a complex, long-range regulatory context

摘要: Single nucleotide polymorphisms (SNPs) within a genetic region including the first two introns of gene encoding FTO have consistently been shown to be strongest factors influencing body mass index (BMI). However, this same also contains several regulatory DNA elements that affect expression IRX3 and IRX5, which respectively, are located approximately 500 kb 1.2 Mbp downstream from BMI-associated locus. Through these affected elements, variation at locus influences adipocyte development leading decreased thermogenesis increased lipid storage. These findings provide genomic model for functional implications variations locus, demonstrate importance accounting chromatin-chromatin interactions when constructing hypotheses mechanisms trait disease-associated common variants. Several consortia generated genome-wide datasets describing different aspects chromatin biology can utilized predict functionality propose biologically relevant descriptions specific regions. Here, we review some publically available data resources on genome function organization used gain an overview regions interest generate testable future studies. We use BMI- obesity-associated as subject it poses illustrative example value resources. find public databases strongly support long-range between in with IRXB cluster genes IRX5. Chromatin configuration capture across large stretching RPGRIP1L gene, cluster.