Research progress in allele-specific expression and its regulatory mechanisms

Gaur, Uma; Li, Kui; Mei, Shuqi; Liu, Guisheng

doi:10.1007/s13353-013-0148-y

Cited by 62 publications

(46 citation statements)

References 172 publications

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“…Finally, the strong selection imprint observed in these P450s might explain their unexpected under transcription in the Perm-R strain. Indeed, the apparent under expression of transcripts affected by differential SNPs might be the consequence of a mapping bias due to a higher divergence from the reference genome or an enrichment in low-expressed alleles [65,66]. Although further analyses are required for investigating the role of allele-specific expression in resistance, our data supports the selection of particular detoxification enzyme variants by insecticides.…”

Section: Discussionmentioning

confidence: 61%

Comparative analysis of response to selection with three insecticides in the dengue mosquito Aedes aegypti using mRNA sequencing

et al. 2014

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BackgroundMosquito control programmes using chemical insecticides are increasingly threatened by the development of resistance. Such resistance can be the consequence of changes in proteins targeted by insecticides (target site mediated resistance), increased insecticide biodegradation (metabolic resistance), altered transport, sequestration or other mechanisms. As opposed to target site resistance, other mechanisms are far from being fully understood. Indeed, insecticide selection often affects a large number of genes and various biological processes can hypothetically confer resistance. In this context, the aim of the present study was to use RNA sequencing (RNA-seq) for comparing transcription level and polymorphism variations associated with adaptation to chemical insecticides in the mosquito Aedes aegypti. Biological materials consisted of a parental susceptible strain together with three child strains selected across multiple generations with three insecticides from different classes: the pyrethroid permethrin, the neonicotinoid imidacloprid and the carbamate propoxur.ResultsAfter ten generations, insecticide-selected strains showed elevated resistance levels to the insecticides used for selection. RNA-seq data allowed detecting over 13,000 transcripts, of which 413 were differentially transcribed in insecticide-selected strains as compared to the susceptible strain. Among them, a significant enrichment of transcripts encoding cuticle proteins, transporters and enzymes was observed. Polymorphism analysis revealed over 2500 SNPs showing > 50% allele frequency variations in insecticide-selected strains as compared to the susceptible strain, affecting over 1000 transcripts. Comparing gene transcription and polymorphism patterns revealed marked differences among strains. While imidacloprid selection was linked to the over transcription of many genes, permethrin selection was rather linked to polymorphism variations. Focusing on detoxification enzymes revealed that permethrin selection strongly affected the polymorphism of several transcripts encoding cytochrome P450 monooxygenases likely involved in insecticide biodegradation.ConclusionsThe present study confirmed the power of RNA-seq for identifying concomitantly quantitative and qualitative transcriptome changes associated with insecticide resistance in mosquitoes. Our results suggest that transcriptome modifications can be selected rapidly by insecticides and affect multiple biological functions. Previously neglected by molecular screenings, polymorphism variations of detoxification enzymes may play an important role in the adaptive response of mosquitoes to insecticides.

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Section: Discussionmentioning

confidence: 61%

Comparative analysis of response to selection with three insecticides in the dengue mosquito Aedes aegypti using mRNA sequencing

et al. 2014

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“…Although RNA-seq is more affordable and can generate gene expression and variant data concomitantly, this approach is not suitable for identifying CNVs and does not provide reliable polymorphism data from poorly expressed genes. In addition, allele frequencies inferred from RNA-seq are to be taken with caution because they can be altered by allele-specific expression events (Gaur et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing

et al. 2015

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The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.

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“…• Отсутствуют унифицированные алгоритмы выяв-ления аллель-специфической экспрессии, что при-водит к существенным различиям в результатах, затрудняющим их сопоставление (например, доля генов, экспрессия которых в норме носит аллель-специфический характер, по разным данным, варь ирует от 0,5 [26] до 20-30 % [6,7]). …”

Section: заключениеunclassified

“…Аллель-специфическая экспрессия и ее механизмы По разным оценкам аллель-специфическая экс-прессия затрагивает от 20 до 30 % генов человека [6,7]. Она может носить тканеспецифичный характер, при этом паттерны такой экспрессии ближе всего в тканях, имеющих сходную функцию или общее происхожде-ние [6].…”

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“…Наиболее распространенны-ми, по-видимому, являются цис-регуляторные поли-морфизмы в некодирующих участках гена (промо-торах, интронах или 3'-нетранслируемых областях). Такие полиморфизмы способны влиять на инициа-цию, скорость транскрипции, альтернативный сплай-синг или стабильность транскрипта конкретного ал-леля [7]. В литературе описано аллель-специфическое связывание транскрипционных факторов, в частности NF-κB и CTCF, в случаях, когда полиморфизм затра-гивает связывающие их мотивы, повышая аффинность транс крипционного фактора к сайту связывания и тем самым изменяя уровень экспрессии гена [8,9].…”

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