74
edits
Changes
no edit summary
It has become widely accepted in science[https://en.wikipedia.org/wiki/RNA#cite_note-1 <sup>[1</sup>]] that early in the [https://en.wikipedia.org/wiki/History_of_life_on_Earth history of life on Earth], prior to the evolution of DNA and possibly of protein-based [https://en.wikipedia.org/wiki/Enzyme enzymes] as well, an "[https://en.wikipedia.org/wiki/RNA_world RNA world]" existed in which RNA served as both living organisms' storage method for [https://en.wikipedia.org/wiki/Genetic_information genetic information]—a role fulfilled today by DNA, except in the case of [https://en.wikipedia.org/wiki/RNA_virus RNA viruses]—and potentially performed catalytic functions in cells—a function performed today by protein enzymes, with the notable and important exception of the ribosome, which is a [https://en.wikipedia.org/wiki/Ribozyme ribozyme].<br/> <br/> Full text link : [https://en.wikipedia.org/wiki/RNA https://en.wikipedia.org/wiki/RNA]
=== eQTL ===
'''Distant and local, trans- and cis-eQTLs, respectively''' An expression quantitative trait is an amount of an [https://en.wikipedia.org/wiki/MRNA mRNA] transcript or a [https://en.wikipedia.org/wiki/Protein protein]. These are usually the product of a single [https://en.wikipedia.org/wiki/Gene gene] with a specific chromosomal location. This distinguishes expression quantitative traits from most [https://en.wikipedia.org/wiki/Complex_traits complex traits], which are not the product of the expression of a single gene. Chromosomal loci that explain variance in expression traits are called eQTLs. eQTLs located near the gene-of-origin (gene which produces the transcript or protein) are referred to as '''local eQTLs''' or '''cis-eQTLs.''' By contrast, those located distant from their gene of origin, often on different chromosomes, are referred to as '''distant eQTLs''' or '''trans-eQTLs'''.[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-Fairfax2012-3 <sup>[3<br/sup> ]] [https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-4 <brsup>[4</sup>]] The first genome-wide study of gene expression was carried out in yeast and published in 2002.[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-Brem2002-5 <sup> [5</sup>]] The initial wave of eQTL studies employed microarrays to measure genome-wide gene expression; more recent studies have employed massively parallel [https://en.wikipedia.org/wiki/RNA-Seq RNA sequencing]. Many [https://en.wikipedia.org/wiki/Gene_expression expression] QTL studies were performed in plants and animals, including humans,[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-6 <sup>[6</sup>]] non-human primates[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-7 <sup>[7</sup>]][https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-8 <sup>[8</sup>]] and mice.[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-9 <sup>[9</sup>]] Some cis eQTLs are detected in many [https://en.wikipedia.org/wiki/Tissue_(biology) tissue] types but the majority of trans eQTLs are tissue-dependent (dynamic).[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-10 <sup>[10</sup>]] eQTLs may act in [https://en.wikipedia.org/wiki/Cis-acting cis] (locally) or [https://en.wikipedia.org/wiki/Trans-acting trans] (at a distance) to a [https://en.wikipedia.org/wiki/Gene gene].[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-11 <sup>[11</sup>]] The abundance of a gene [https://en.wikipedia.org/wiki/RNA transcript] is directly modified by [https://en.wikipedia.org/wiki/Polymorphism_(biology) polymorphism] in [https://en.wikipedia.org/wiki/Regulatory_elements regulatory elements]. Consequently, transcript abundance might be considered as a quantitative trait that can be mapped with considerable power. These have been named expression [https://en.wikipedia.org/wiki/QTL QTLs] (eQTLs).[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-12 <sup>[12</sup>]] The combination of [https://en.wikipedia.org/wiki/Genome-wide_association_study whole-genome genetic association studies] and the measurement of global [https://en.wikipedia.org/wiki/Gene_expression gene expression] allows the systematic identification of eQTLs. By assaying gene expression and [https://en.wikipedia.org/wiki/Genetic_variation genetic variation] simultaneously on a genome-wide basis in a large number of individuals, statistical genetic methods can be used to map the genetic factors that underpin individual differences in quantitative levels of expression of many thousands of transcripts.[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-13 <sup>[13</sup>]] Studies have shown that [https://en.wikipedia.org/wiki/Single_nucleotide_polymorphism single nucleotide polymorphisms] (SNPs) reproducibly associated with complex disorders [https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-14 <sup>[14</sup>]] as well as certain pharmacologic phenotypes [https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-15 <sup>[15</sup>]] are found to be significantly enriched for eQTLs, relative to frequency-matched control SNPs. The integration of eQTLs with [https://en.wikipedia.org/wiki/Genome-wide_association_study GWAS] has led to development of the [https://en.wikipedia.org/wiki/Transcriptome-wide_association_study transcriptome-wide association study] (TWAS) methodology.[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-16 <sup>[16</sup>]][https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-17 <sup>[17</sup>]] '''Detecting eQTLs''' Mapping eQTLs is done using standard [https://en.wikipedia.org/wiki/QTL QTL] mapping methods that test the linkage between variation in expression and genetic polymorphisms. The only considerable difference is that eQTL studies can involve a million or more expression microtraits. Standard gene mapping software packages can be used, although it is often faster to use custom code such as QTL Reaper or the web-based eQTL mapping system [https://en.wikipedia.org/wiki/GeneNetwork GeneNetwork]. GeneNetwork hosts many large eQTL mapping data sets and provide access to fast algorithms to map single loci and [https://en.wikipedia.org/wiki/Epistasis epistatic] interactions. As is true in all QTL mapping studies, the final steps in defining DNA variants that cause variation in traits are usually difficult and require a second round of experimentation. This is especially the case for trans eQTLs that do not benefit from the strong prior probability that relevant variants are in the immediate vicinity of the parent gene. Statistical, graphical, and bioinformatic methods are used to evaluate positional candidate genes and entire systems of interactions.[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-Kulp_2006-18 <sup>[18</sup>]][https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-Lee_2009-19 <sup>[19</sup>]] The development of single cell technologies, and parallel advances in statistical methods has made it possible to define even subtle changes in eQTLs as cell-states change.[https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-20 <sup>[20</sup>]][https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci#cite_note-21 <sup>[21</sup>]] Full text link : [https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci https://en.wikipedia.org/wiki/Expression_quantitative_trait_loci]<br/> <br/> <br/> <br/> <br/> <br/> <br/> [https://biolecture.org/Main_Page Main Page] » [https://biolecture.org/UNIST_Geromics_course UNIST Geromics course] » [https://biolecture.org/Geromics_Course_Students_Folder_2024 Geromics Course Students Folder 2024] » [https://biolecture.org/HyoungJinChoi_2024_Geromics_Course HyoungJinChoi 2024 Geromics Course] » [https://biolecture.org/Summary_class_Geromics_2024_HyoungJinChoi Summary class Geromics 2024 HyoungJinCho]