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The genetic architecture of gene expression levels in wild baboons.

Tung J, Zhou X, Alberts SC, Stephens M, Gilad Y - Elife (2015)

Bottom Line: Primate evolution has been argued to result, in part, from changes in how genes are regulated.We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set.Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, United States.

ABSTRACT
Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates.

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Detection of ASE is not dependent on number of heterozygotes,conditional on total read depth.SNPs within the set tested for ASE (n = 8145) were divided intodeciles based on total read depth. The evidence for a relationship(−log10 of the p-value from a Wilcoxon test) betweennumber of heterozygous individuals at each site and detection ofsignificant ASE is shown on the y-axis for each decile. Dashed line showsa nominal significance threshold of p = 0.01. Blue numbers aboveeach point show the number of sites that fall within the decile; purplenumbers below each point show the maximum total read depth for thatdecile (minimum total read depth is the maximum depth for the previousdecile, or 300 for the lowest decile).DOI:http://dx.doi.org/10.7554/eLife.04729.017
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fig1s14: Detection of ASE is not dependent on number of heterozygotes,conditional on total read depth.SNPs within the set tested for ASE (n = 8145) were divided intodeciles based on total read depth. The evidence for a relationship(−log10 of the p-value from a Wilcoxon test) betweennumber of heterozygous individuals at each site and detection ofsignificant ASE is shown on the y-axis for each decile. Dashed line showsa nominal significance threshold of p = 0.01. Blue numbers aboveeach point show the number of sites that fall within the decile; purplenumbers below each point show the maximum total read depth for thatdecile (minimum total read depth is the maximum depth for the previousdecile, or 300 for the lowest decile).DOI:http://dx.doi.org/10.7554/eLife.04729.017

Mentions: To identify ASE, we focused on SNPs within gene exons with Phred-scaled qualityscores greater than 10. We further required that these sites have more than fivereads in more than two individuals and more than 300 total reads across allheterozygous individuals. This threshold is based on the observation that the powerto detect ASE is dependent on sequencing read coverage at heterozygous sites (Fontanillas et al., 2010). Indeed, in our dataset, power to detect ASE appeared to scale primarily with total read coverage ratherthan number of heterozygous individuals. Sites with more reads tended to have moreheterozygotes (r = 0.266, p < 10−100); however, whensites were partitioned by total read depth (in deciles), sites with significant ASEwere not more likely to harbor more heterozygotes in any decile (Wilcoxon testcomparing number of heterozygotes in significant sites vs background; Figure 1—figure supplement 14).


The genetic architecture of gene expression levels in wild baboons.

Tung J, Zhou X, Alberts SC, Stephens M, Gilad Y - Elife (2015)

Detection of ASE is not dependent on number of heterozygotes,conditional on total read depth.SNPs within the set tested for ASE (n = 8145) were divided intodeciles based on total read depth. The evidence for a relationship(−log10 of the p-value from a Wilcoxon test) betweennumber of heterozygous individuals at each site and detection ofsignificant ASE is shown on the y-axis for each decile. Dashed line showsa nominal significance threshold of p = 0.01. Blue numbers aboveeach point show the number of sites that fall within the decile; purplenumbers below each point show the maximum total read depth for thatdecile (minimum total read depth is the maximum depth for the previousdecile, or 300 for the lowest decile).DOI:http://dx.doi.org/10.7554/eLife.04729.017
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383332&req=5

fig1s14: Detection of ASE is not dependent on number of heterozygotes,conditional on total read depth.SNPs within the set tested for ASE (n = 8145) were divided intodeciles based on total read depth. The evidence for a relationship(−log10 of the p-value from a Wilcoxon test) betweennumber of heterozygous individuals at each site and detection ofsignificant ASE is shown on the y-axis for each decile. Dashed line showsa nominal significance threshold of p = 0.01. Blue numbers aboveeach point show the number of sites that fall within the decile; purplenumbers below each point show the maximum total read depth for thatdecile (minimum total read depth is the maximum depth for the previousdecile, or 300 for the lowest decile).DOI:http://dx.doi.org/10.7554/eLife.04729.017
Mentions: To identify ASE, we focused on SNPs within gene exons with Phred-scaled qualityscores greater than 10. We further required that these sites have more than fivereads in more than two individuals and more than 300 total reads across allheterozygous individuals. This threshold is based on the observation that the powerto detect ASE is dependent on sequencing read coverage at heterozygous sites (Fontanillas et al., 2010). Indeed, in our dataset, power to detect ASE appeared to scale primarily with total read coverage ratherthan number of heterozygous individuals. Sites with more reads tended to have moreheterozygotes (r = 0.266, p < 10−100); however, whensites were partitioned by total read depth (in deciles), sites with significant ASEwere not more likely to harbor more heterozygotes in any decile (Wilcoxon testcomparing number of heterozygotes in significant sites vs background; Figure 1—figure supplement 14).

Bottom Line: Primate evolution has been argued to result, in part, from changes in how genes are regulated.We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set.Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, United States.

ABSTRACT
Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates.

Show MeSH