Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of <em>IRX3</em> and <em>IRX5</em>

doi:10.1126/science.abf1008

GSTDTAP > 气候变化

DOI	10.1126/science.abf1008
	Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5
	Débora R. Sobreira; Amelia C. Joslin; Qi Zhang; Iain Williamson; Grace T. Hansen; Kathryn M. Farris; Noboru J. Sakabe; Nasa Sinnott-Armstrong; Grazyna Bozek; Sharon O. Jensen-Cody; Kyle H. Flippo; Carole Ober; Wendy A. Bickmore; Matthew Potthoff; Mengjie Chen; Melina Claussnitzer; Ivy Aneas; Marcelo A. Nóbrega
	2021-06-04
发表期刊	Science
出版年	2021
英文摘要	The biological causes of obesity are not well understood. Sobreira et al. examined the chromatin interactions between key genes in a locus known for its associations with obesity in human patients. In addition to directly interrogating the connections between these genes and examining the mechanisms that regulate their activity, the authors used mouse models to study the target genes' effects on both adipose tissue and brain cells that play a role in regulating dietary preferences. Science , abf1008, this issue p. [1085][1] Whereas coding variants often have pleiotropic effects across multiple tissues, noncoding variants are thought to mediate their phenotypic effects by specific tissue and temporal regulation of gene expression. Here, we investigated the genetic and functional architecture of a genomic region within the FTO gene that is strongly associated with obesity risk. We show that multiple variants on a common haplotype modify the regulatory properties of several enhancers targeting IRX3 and IRX5 from megabase distances. We demonstrate that these enhancers affect gene expression in multiple tissues, including adipose and brain, and impart regulatory effects during a restricted temporal window. Our data indicate that the genetic architecture of disease-associated loci may involve extensive pleiotropy, allelic heterogeneity, shared allelic effects across tissues, and temporally restricted effects. [1]: /lookup/doi/10.1126/science.abf1008
领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：48[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/329875
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Débora R. Sobreira,Amelia C. Joslin,Qi Zhang,et al. Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5[J]. Science,2021.
APA	Débora R. Sobreira.,Amelia C. Joslin.,Qi Zhang.,Iain Williamson.,Grace T. Hansen.,...&Marcelo A. Nóbrega.(2021).Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5.Science.
MLA	Débora R. Sobreira,et al."Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5".Science (2021).