scholarly journals Allele-specific expression reveals interactions between genetic variation and environment

2015 ◽  
Author(s):  
David A Knowles ◽  
Joe R Davis ◽  
Anil Raj ◽  
Xiaowei Zhu ◽  
James B Potash ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Cellular Level ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Sequencing Studies ◽  
Allele Specific ◽  
Gxe Interactions ◽  
Over Dispersion ◽  
The Impact

The impact of environment on human health is dramatic, with major risk factors including substance use, diet and exercise. However, identifying interactions between the environment and an individual's genetic background (GxE) has been hampered by statistical and computational challenges. By combining RNA sequencing of whole blood and extensive environmental annotations collected from 922 individuals, we have evaluated GxE interactions at a cellular level. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on association between environment and allele-specific expression (ASE). EAGLE increases power by leveraging the controlled, within-sample comparison of environmental impact on different genetic backgrounds provided by ASE, while also taking into account technical covariates and over-dispersion of sequencing read counts. EAGLE identifies 35 GxE interactions, a substantial increase over standard GxE testing. Among EAGLE hits are variants that modulate response to smoking, exercise and blood pressure medication. Further, application of EAGLE identifies GxE interactions to infection response that replicate results reported in vitro, demonstrating the power of EAGLE to accurately identify GxE candidates from large RNA sequencing studies.

scholarly journals Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain

Neuron ◽  
2017 ◽  
Vol 93 (5) ◽  
pp. 1094-1109.e7 ◽  
Author(s):  
Wei-Chao Huang ◽  
Elliott Ferris ◽  
Tong Cheng ◽  
Cornelia Stacher Hörndli ◽  
Kelly Gleason ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Cellular Level ◽  
Mammalian Brain ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

scholarly journals Transposable elements that have recently been mobile in the human genome

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Matias I. Autio ◽  
Talal Bin Amin ◽  
Arnaud Perrin ◽  
Jen Yi Wong ◽  
Roger S.-Y. Foo ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Human Genome ◽  
Genetic Disorders ◽  
Statistical Test ◽  
Population History ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific ◽  
Regulatory Potential

Abstract Background Transposable elements (TE) comprise nearly half of the human genome and their insertions have profound effects to human genetic diversification and as well as disease. Despite their abovementioned significance, there is no consensus on the TE subfamilies that remain active in the human genome. In this study, we therefore developed a novel statistical test for recently mobile subfamilies (RMSs), based on patterns of overlap with > 100,000 polymorphic indels. Results Our analysis produced a catalogue of 20 high-confidence RMSs, which excludes many false positives in public databases. Intriguingly though, it includes HERV-K, an LTR subfamily previously thought to be extinct. The RMS catalogue is strongly enriched for contributions to germline genetic disorders (P = 1.1e-10), and thus constitutes a valuable resource for diagnosing disorders of unknown aetiology using targeted TE-insertion screens. Remarkably, RMSs are also highly enriched for somatic insertions in diverse cancers (P = 2.8e-17), thus indicating strong correlations between germline and somatic TE mobility. Using CRISPR/Cas9 deletion, we show that an RMS-derived polymorphic TE insertion increased the expression of RPL17, a gene associated with lower survival in liver cancer. More broadly, polymorphic TE insertions from RMSs were enriched near genes with allele-specific expression, suggesting widespread effects on gene regulation. Conclusions By using a novel statistical test we have defined a catalogue of 20 recently mobile transposable element subfamilies. We illustrate the gene regulatory potential of RMS-derived polymorphic TE insertions, using CRISPR/Cas9 deletion in vitro on a specific candidate, as well as by genome wide analysis of allele-specific expression. Our study presents novel insights into TE mobility and regulatory potential and provides a key resource for human disease genetics and population history studies.

scholarly journals An in vitro ES cell imprinting model shows that imprinted expression of the Igf2r gene arises from an allele-specific expression bias

Development ◽  
2009 ◽  
Vol 136 (3) ◽  
pp. 437-448 ◽  
Author(s):  
P. A. Latos ◽  
S. H. Stricker ◽  
L. Steenpass ◽  
F. M. Pauler ◽  
R. Huang ◽  
...  
Keyword(s):  
Es Cell ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Expression Bias ◽  
Allele Specific

scholarly journals Effect of read-mapping biases on detecting allele-specific expression from RNA-sequencing data

2009 ◽  
Vol 25 (24) ◽  
pp. 3207-3212 ◽  
Author(s):  
Jacob F. Degner ◽  
John C. Marioni ◽  
Athma A. Pai ◽  
Joseph K. Pickrell ◽  
Everlyne Nkadori ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Sequencing Data ◽  
Read Mapping ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

239 ALLELE-SPECIFIC EXPRESSION OF X CHROMOSOME-LINKED GENE MAO-A DURING PRE-IMPLANTATION DEVELOPMENT IN BOVINE EMBRYO

2010 ◽  
Vol 22 (1) ◽  
pp. 277
Author(s):  
A. R. Ferreira ◽  
G. M. Machado ◽  
T. O. Diesel ◽  
J. O. Carvalho ◽  
R. Rumpf ◽  
...  
Keyword(s):  
X Chromosome ◽  
Bos Taurus ◽  
Paternal Allele ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
X Chromosomes ◽  
Linked Gene ◽  
Mao A ◽  
Allele Specific

The in vitro embryo culture might affect epigenetic mechanisms, which are involved in controlling the expression of genes related to embryonic development and inactivation of X chromosome. Female mammals have 2 X chromosomes, and males have only 1. This has led to a particular mechanism of evolution of dosage compensation, called X-chromosome inactivation, an important epigenetic event that must occur in all mammalian female embryos. During embryogenesis, at the late blastocyst development (Xue F et al. 2002 Nature Genet. 31, 216–220), 1 of the 2 X chromosomes is randomly inactivated in each cell of the inner cell mass and preferentially X paternal in trophoblast. The aim of this study was to characterize the allele-specific expression of the X chromosome-linked gene monoamine oxidase type A (MAO-A) during in vitro pre-implantation embryo development in bovine. For phenotyping of the MAO-A gene, the RT-PCR restriction fragment length polymorphism technique was used. Primers were designed flanking a single nucleotide polymorphism and the sequence of forward inner primer creating a site of restriction to the RsaI enzyme, thus allowing the detection of allele-specific expression (Bos taurus Taurus × Bos taurus indicus). Oocytes were aspirated from 9 Nelore heifers homozygous for theA allele previously genotyped. The oocytes were selected, matured in vitro, and inseminated with X-sorted sperm from a Holstein bull homozygous for the G allele. Two pools of 10 heterozygous in vitro embryos of each developmental stage, 4-cell [44 h post-insemination (p.i.)], 8- to 16-cell (72 h p.i.), morula (144 h p.i.), blastocyst (156 p.i.), and expanded blastocyst (168 h p.i.), were produced and frozen until RNA extraction. Total RNA was extracted using Invisorb® Spin Cell RNA Mini Kit (Invitek, Berlin, Germany) according to the manufacturer’s protocol, and residual genomic DNA was removed with DNase I treatment. cDNA was done using Oligo dT primers (Invitrogen) and superscript III reverse transcriptase (Invitrogen). Nested PCR for each pool was performed and then the amplicons were digested with 10 U of RsaI enzyme (Promega, Madison, WI, USA). The products were separated by electrophoresis on a 3% agarose gel stained with ethidium bromide. The results showed that both alleles were expressionally represented in the 4-cell, 8- to 16-cell, and expanded blastocyst stages, with the X paternal allele disappearing in morula and blastocyst. We can conclude that both, maternal and paternal X chromosomes, are activated in the 2 earliest stages, inactivated in the morula and blastocyst stages, and reactivated in the expanded blastocyst stage. This research was supported by Embrapa Genetic Resources and Biotechnology and the Brazilian National Council for Scientific and Technological Development (CNPq).

Allele-specific expression of the serotonin transporter and its transcription factors following lamotrigine treatment in vitro

2013 ◽  
Vol 162 (5) ◽  
pp. 474-483 ◽  
Author(s):  
Ursula M. D'Souza ◽  
Georgia Powell-Smith ◽  
Kate Haddley ◽  
Timothy R. Powell ◽  
Vivien J. Bubb ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Serotonin Transporter ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific

scholarly journals RNA-Seq Data for Reliable SNP Detection and Genotype Calling: Interest for Coding Variant Characterization and Cis-Regulation Analysis by Allele-Specific Expression in Livestock Species

2021 ◽  
Vol 12 ◽  
Author(s):  
Frédéric Jehl ◽  
Fabien Degalez ◽  
Maria Bernard ◽  
Frédéric Lecerf ◽  
Laetitia Lagoutte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Call Rate ◽  
Rna Seq ◽  
Snp Detection ◽  
Specific Expression ◽  
Genotype Calling ◽  
Allele Specific Expression ◽  
Livestock Species ◽  
Allele Specific ◽  
The Impact

In addition to their common usages to study gene expression, RNA-seq data accumulated over the last 10 years are a yet-unexploited resource of SNPs in numerous individuals from different populations. SNP detection by RNA-seq is particularly interesting for livestock species since whole genome sequencing is expensive and exome sequencing tools are unavailable. These SNPs detected in expressed regions can be used to characterize variants affecting protein functions, and to study cis-regulated genes by analyzing allele-specific expression (ASE) in the tissue of interest. However, gene expression can be highly variable, and filters for SNP detection using the popular GATK toolkit are not yet standardized, making SNP detection and genotype calling by RNA-seq a challenging endeavor. We compared SNP calling results using GATK suggested filters, on two chicken populations for which both RNA-seq and DNA-seq data were available for the same samples of the same tissue. We showed, in expressed regions, a RNA-seq precision of 91% (SNPs detected by RNA-seq and shared by DNA-seq) and we characterized the remaining 9% of SNPs. We then studied the genotype (GT) obtained by RNA-seq and the impact of two factors (GT call-rate and read number per GT) on the concordance of GT with DNA-seq; we proposed thresholds for them leading to a 95% concordance. Applying these thresholds to 767 multi-tissue RNA-seq of 382 birds of 11 chicken populations, we found 9.5 M SNPs in total, of which ∼550,000 SNPs per tissue and population with a reliable GT (call rate ≥ 50%) and among them, ∼340,000 with a MAF ≥ 10%. We showed that such RNA-seq data from one tissue can be used to (i) detect SNPs with a strong predicted impact on proteins, despite their scarcity in each population (16,307 SIFT deleterious missenses and 590 stop-gained), (ii) study, on a large scale, cis-regulations of gene expression, with ∼81% of protein-coding and 68% of long non-coding genes (TPM ≥ 1) that can be analyzed for ASE, and with ∼29% of them that were cis-regulated, and (iii) analyze population genetic using such SNPs located in expressed regions. This work shows that RNA-seq data can be used with good confidence to detect SNPs and associated GT within various populations and used them for different analyses as GTEx studies.

scholarly journals ASEP: Gene-based detection of allele-specific expression across individuals in a population by RNA sequencing

PLoS Genetics ◽  
2020 ◽  
Vol 16 (5) ◽  
pp. e1008786 ◽  
Author(s):  
Jiaxin Fan ◽  
Jian Hu ◽  
Chenyi Xue ◽  
Hanrui Zhang ◽  
Katalin Susztak ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific
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