Neuropsychiatric disorders affect hundreds of millions of patients and families worldwide.To decode the molecular framework of these diseases,many studies use human postmortem brain samples.These studies reveal brain-...Neuropsychiatric disorders affect hundreds of millions of patients and families worldwide.To decode the molecular framework of these diseases,many studies use human postmortem brain samples.These studies reveal brain-specific genetic and epigenetic patterns via highthroughput sequencing technologies.Identifying best practices for the collection of postmortem brain samples,analyzing such large amounts of sequencing data,and interpreting these results are critical to advance neuropsychiatry.We provide an overview of human brain banks worldwide,including progress in China,highlighting some well-known projects using human postmortem brain samples to understand molecular regulation in both normal brains and those with neuropsychiatric disorders.Finally,we discuss future research strategies,as well as state-of-the-art statistical and experimental methods that are drawn upon brain bank resources to improve our understanding of the agents of neuropsychiatric disorders.展开更多
Gene expression regulation plays an important role in controlling plant phenotypes and adaptation. Here, we report a comprehensive assessment of gene expression variation through the transcriptome analyses of a large ...Gene expression regulation plays an important role in controlling plant phenotypes and adaptation. Here, we report a comprehensive assessment of gene expression variation through the transcriptome analyses of a large maize-teosinte experimental population. Genome-wide mapping identified 25 660 expression quantitative trait loci （eQTL） for 17 311 genes, capturing an unprecedented range of expression variation. We found that local eQTL were more frequently mapped to adjacent genes, displaying a mode of expression piggybacking, which consequently created co-regulated gene clusters. Genes within the co-regulated gene clusters tend to have relevant functions and shared chromatin modifications. Distant eQTL formed 125 significant distant eQTL hotspots with their targets significantly enriched in specific functional cate- gories. By integrating different sources of information, we identified putative trans- regulators for a variety of metabolic pathways. We demonstrated that the bHLH transcription factor R1 and hexokinase HEX9 might act as crucial regulators for flavonoid biosynthesis and glycolysis, respectively. Moreover, we showed that domestication or improvement has significantly affected global gene expression, with many genes targeted by selection. Of particular interest, the Bx genes for benzoxazinoid biosynthesis may have undergone coordinated cis-regulatory divergence between maize and teosinte, and a transposon insertion that inactivates Bx12 was under strong selection as maize spread into temperate environments with a distinct herbivore community.展开更多
Gene expression is a critical process in biological system that is influenced and modulated by many factors including genetic variation. Expression Quantitative Trait Loci（e QTL） analysis provides a powerful way to ...Gene expression is a critical process in biological system that is influenced and modulated by many factors including genetic variation. Expression Quantitative Trait Loci（e QTL） analysis provides a powerful way to understand how genetic variants affect gene expression. For genome wide e QTL analysis, the number of genetic variants and that of genes are large and thus the search space is tremendous. Therefore, e QTL analysis brings about computational and statistical challenges. In this paper, we provide a comprehensive review of recent advances in methods for e QTL analysis in population-based studies. We first present traditional pairwise association methods, which are widely used in human genetics. To account for expression heterogeneity, we investigate the methods for correcting confounding factors. Next, we discuss newly developed statistical learning methods including Lasso-based models. In the conclusion, we provide an overview of future method development in analyzing e QTL associations. Although we focus on human genetics in this review, the methods are applicable to many other organisms.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.31571312,31970572,and81401114)the National Key R&D Project of China(Grant No.2016YFC1306000)Innovation-driven Project of Central South University(Grant Nos.2015CXS034 and 2018CX033)to CC
文摘Neuropsychiatric disorders affect hundreds of millions of patients and families worldwide.To decode the molecular framework of these diseases,many studies use human postmortem brain samples.These studies reveal brain-specific genetic and epigenetic patterns via highthroughput sequencing technologies.Identifying best practices for the collection of postmortem brain samples,analyzing such large amounts of sequencing data,and interpreting these results are critical to advance neuropsychiatry.We provide an overview of human brain banks worldwide,including progress in China,highlighting some well-known projects using human postmortem brain samples to understand molecular regulation in both normal brains and those with neuropsychiatric disorders.Finally,we discuss future research strategies,as well as state-of-the-art statistical and experimental methods that are drawn upon brain bank resources to improve our understanding of the agents of neuropsychiatric disorders.
文摘Gene expression regulation plays an important role in controlling plant phenotypes and adaptation. Here, we report a comprehensive assessment of gene expression variation through the transcriptome analyses of a large maize-teosinte experimental population. Genome-wide mapping identified 25 660 expression quantitative trait loci （eQTL） for 17 311 genes, capturing an unprecedented range of expression variation. We found that local eQTL were more frequently mapped to adjacent genes, displaying a mode of expression piggybacking, which consequently created co-regulated gene clusters. Genes within the co-regulated gene clusters tend to have relevant functions and shared chromatin modifications. Distant eQTL formed 125 significant distant eQTL hotspots with their targets significantly enriched in specific functional cate- gories. By integrating different sources of information, we identified putative trans- regulators for a variety of metabolic pathways. We demonstrated that the bHLH transcription factor R1 and hexokinase HEX9 might act as crucial regulators for flavonoid biosynthesis and glycolysis, respectively. Moreover, we showed that domestication or improvement has significantly affected global gene expression, with many genes targeted by selection. Of particular interest, the Bx genes for benzoxazinoid biosynthesis may have undergone coordinated cis-regulatory divergence between maize and teosinte, and a transposon insertion that inactivates Bx12 was under strong selection as maize spread into temperate environments with a distinct herbivore community.
基金supported in part by a Faculty Research Grant from the University of North Carolina at Charlotte
文摘Gene expression is a critical process in biological system that is influenced and modulated by many factors including genetic variation. Expression Quantitative Trait Loci（e QTL） analysis provides a powerful way to understand how genetic variants affect gene expression. For genome wide e QTL analysis, the number of genetic variants and that of genes are large and thus the search space is tremendous. Therefore, e QTL analysis brings about computational and statistical challenges. In this paper, we provide a comprehensive review of recent advances in methods for e QTL analysis in population-based studies. We first present traditional pairwise association methods, which are widely used in human genetics. To account for expression heterogeneity, we investigate the methods for correcting confounding factors. Next, we discuss newly developed statistical learning methods including Lasso-based models. In the conclusion, we provide an overview of future method development in analyzing e QTL associations. Although we focus on human genetics in this review, the methods are applicable to many other organisms.
