Dissection of quantitative trait loci in the Lachancea waltii yeast species highlights major hotspots.
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ABSTRACT:
SUBMITTER: Peltier E
PROVIDER: S-EPMC8496267 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Quantitative trait loci (QTL) hotspots (genomic locations affecting many traits) are a common feature in genetical genomics studies and are biologically interesting since they may harbor critical regulators. Therefore, statistical procedures to assess the significance of hotspots are of key importance. One approach, randomly allocating observed QTL across the genomic locations separately by trait, implicitly assumes all traits are uncorrelated. Recently, an empirical test for QTL hotspots was proposed on the basis of the number of traits that exceed a predetermined LOD value, such as the standard permutation LOD threshold. The permutation null distribution of the maximum number of traits across all genomic locations preserves the correlation structure among the phenotypes, avoiding the detection of spurious hotspots due to nongenetic correlation induced by uncontrolled environmental factors and unmeasured variables. However, by considering only the number of traits above a threshold, without accounting for the magnitude of the LOD scores, relevant information is lost. In particular, biologically interesting hotspots composed of a moderate to small number of traits with strong LOD scores may be neglected as nonsignificant. In this article we propose a quantile-based permutation approach that simultaneously accounts for the number and the LOD scores of traits within the hotspots. By considering a sliding scale of mapping thresholds, our method can assess the statistical significance of both small and large hotspots. Although the proposed approach can be applied to any type of heritable high-volume "omic" data set, we restrict our attention to expression (e)QTL analysis. We assess and compare the performances of these three methods in simulations and we illustrate how our approach can effectively assess the significance of moderate and small hotspots with strong LOD scores in a yeast expression data set.
| S-EPMC3416013 | biostudies-literature
Project description:Several quantitative trait loci (QTL) mapping strategies can successfully identify major-effect loci, but often have poor success detecting loci with minor effects, potentially due to the confounding effects of major loci, epistasis, and limited sample sizes. To overcome such difficulties, we used a targeted backcross mapping strategy that genetically eliminated the effect of a previously identified major QTL underlying high-temperature growth (Htg) in yeast. This strategy facilitated the mapping of three novel QTL contributing to Htg of a clinically derived yeast strain. One QTL, which is linked to the previously identified major-effect QTL, was dissected, and NCS2 was identified as the causative gene. The interaction of the NCS2 QTL with the first major-effect QTL was background dependent, revealing a complex QTL architecture spanning these two linked loci. Such complex architecture suggests that more genes than can be predicted are likely to contribute to quantitative traits. The targeted backcrossing approach overcomes the difficulties posed by sample size, genetic linkage, and epistatic effects and facilitates identification of additional alleles with smaller contributions to complex traits.
| S-EPMC2581965 | biostudies-literature
Project description:Evolution of the replication profile in 10 Lachancea species
| PRJNA393002 | ENA
Project description:Background:The frequency of recombination events varies across the genome and between individuals, which may be related to some genomic features. The objective of this study was to assess the frequency of recombination events and to identify QTL (quantitative trait loci) for recombination rate in two purebred layer chicken lines. Methods:A total of 1200 white-egg layers (WL) were genotyped with 580?K SNPs and 5108 brown-egg layers (BL) were genotyped with 42?K SNPs (single nucleotide polymorphisms). Recombination events were identified within half-sib families and both the number of recombination events and the recombination rate was calculated within each 0.5?Mb window of the genome. The 10% of windows with the highest recombination rate on each chromosome were considered to be recombination hotspots. A BayesB model was used separately for each line to identify genomic regions associated with the genome-wide number of recombination event per meiosis. Regions that explained more than 0.8% of genetic variance of recombination rate were considered to harbor QTL. Results:Heritability of recombination rate was estimated at 0.17 in WL and 0.16 in BL. On average, 11.3 and 23.2 recombination events were detected per individual across the genome in 1301 and 9292 meioses in the WL and BL, respectively. The estimated recombination rates differed significantly between the lines, which could be due to differences in inbreeding levels, and haplotype structures. Dams had about 5% to 20% higher recombination rates per meiosis than sires in both lines. Recombination rate per 0.5?Mb window had a strong negative correlation with chromosome size and a strong positive correlation with GC content and with CpG island density across the genome in both lines. Different QTL for recombination rate were identified in the two lines. There were 190 and 199 non-overlapping recombination hotspots detected in WL and BL respectively, 28 of which were common to both lines. Conclusions:Differences in the recombination rates, hotspot locations, and QTL regions associated with genome-wide recombination were observed between lines, indicating the breed-specific feature of detected recombination events and the control of recombination events is a complex polygenic trait.
| S-EPMC6390344 | biostudies-literature
Project description:Functional genomics relies on two essential parameters: the sensitivity of phenotypic measures and the power to detect genomic perturbations that cause phenotypic variations. In model organisms, two types of perturbations are widely used. Artificial mutations can be introduced in virtually any gene and allow the systematic analysis of gene function via mutants fitness. Alternatively, natural genetic variations can be associated to particular phenotypes via genetic mapping. However, the access to genome manipulation and breeding provided by model organisms is sometimes counterbalanced by phenotyping limitations. Here we investigated the natural genetic diversity of Saccharomyces cerevisiae cellular morphology using a very sensitive high-throughput imaging platform. We quantified 501 morphological parameters in over 50,000 yeast cells from a cross between two wild-type divergent backgrounds. Extensive morphological differences were found between these backgrounds. The genetic architecture of the traits was complex, with evidence of both epistasis and transgressive segregation. We mapped quantitative trait loci (QTL) for 67 traits and discovered 364 correlations between traits segregation and inheritance of gene expression levels. We validated one QTL by the replacement of a single base in the genome. This study illustrates the natural diversity and complexity of cellular traits among natural yeast strains and provides an ideal framework for a genetical genomics dissection of multiple traits. Our results did not overlap with results previously obtained from systematic deletion strains, showing that both approaches are necessary for the functional exploration of genomes.
| S-EPMC1802830 | biostudies-literature
Project description:Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat (Triticum aestivum L.). To investigate quantitative trait loci (QTL) associated with SC and SL, a recombinant inbred lines (RIL) population derived from the cross of Bailangmai (BLM, a Tibet landrace) and Chuanyu 20 (CY20, an improved variety) was employed in six environments. Three genomic regions responsible for SC and SL traits were identified on chromosomes 2A and 2D using bulked segregant exome sequencing (BSE-Seq). By constructing genetic maps, six major QTL were repeatedly detected in more than four environments and the best linear unbiased estimation (BLUE) datasets, explaining 7.00-28.56% of the phenotypic variation and the logarithm of the odd (LOD) score varying from 2.50 to 13.22. They were co-located on three loci, designed as QSc/Sl.cib-2AS, QSc/Sl.cib-2AL, and QSc/Sl.cib-2D, respectively. Based on the flanking markers, their interactions and effects on the corresponding trait and other agronomic traits were also analyzed. Comparison analysis showed that QSc/Sl.cib-2AS and QSc/Sl.cib-2AL were possibly two novel loci for SC and SL. QSc/Sl.cib-2AS and QSc/Sl.cib-2D showed pleiotropic effects on plant height and grain morphology, while QSc/Sl.cib-2AL showed effects on spikelet number per spike (SNS) and grain width (GW). Based on the gene annotation, orthologous search, and spatiotemporal expression patterns of genes, TraesCS2A03G0410600 and TraesCS2A03G0422300 for QSc/Sl.cib-2AS, and TraesCS2D03G1129300 and TraesCS2D03G1131500 for QSc/Sl.cib-2D were considered as potential candidate genes, respectively. These results will be useful for fine mapping and developing new varieties with high yield in the future.
| S-EPMC9168683 | biostudies-literature
Project description:In genomewide mapping of expression quantitative trait loci (eQTL), it is widely believed that thousands of genes are trans-regulated by a small number of genomic regions called "regulatory hotspots," resulting in "trans-regulatory bands" in an eQTL map. As several recent studies have demonstrated, technical confounding factors such as batch effects can complicate eQTL analysis by causing many spurious associations including spurious regulatory hotspots. Yet little is understood about how these technical confounding factors affect eQTL analyses and how to correct for these factors. Our analysis of data sets with biological replicates suggests that it is this intersample correlation structure inherent in expression data that leads to spurious associations between genetic loci and a large number of transcripts inducing spurious regulatory hotspots. We propose a statistical method that corrects for the spurious associations caused by complex intersample correlation of expression measurements in eQTL mapping. Applying our intersample correlation emended (ICE) eQTL mapping method to mouse, yeast, and human identifies many more cis associations while eliminating most of the spurious trans associations. The concordances of cis and trans associations have consistently increased between different replicates, tissues, and populations, demonstrating the higher accuracy of our method to identify real genetic effects.
| S-EPMC2600931 | biostudies-literature
Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the âbiological signatureâ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Pairs of Cy5 and Cy3 labeled targets were co-hybridized onto either a custom long oligonucleotide microarray for the interrogation of 231 genes encompassed by QTL1 and QTL2, or a TIGR rat cDNA array consisting of 26,401 probe elements representing 20,465 unique non-QTL genes. A âflip-dyeâ or âbalanced blockâ design was used as the experimental method of choice to account for potential dye-bias labeling effects. Six âbalanced blockâ normalized files are submitted for the long oligonucleotide array interrogating the hearts from S versus S.LEW(5)x6x9 animals, fourteen âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x9 animals, and twelve âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x11 animals. GPR and MEV files cannot be located.
2010-06-25 | E-GEOD-7628 | biostudies-arrayexpress
Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the ‘biological signature’ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Keywords: rat, hypertension, genetics, polygenic trait, microarray, gene expression
2008-03-04 | GSE7628 | GEO
Project description:Distinct floral pollination syndromes have emerged multiple times during the diversification of flowering plants. For example, in western North America, a hummingbird pollination syndrome has evolved more than 100 times, generally from within insect-pollinated lineages. The hummingbird syndrome is characterized by a suite of floral traits that attracts and facilitates pollen movement by hummingbirds, while at the same time discourages bee visitation. These floral traits generally include large nectar volume, red flower colour, elongated and narrow corolla tubes and reproductive organs that are exerted from the corolla. A handful of studies have examined the genetic architecture of hummingbird pollination syndrome evolution. These studies find that mutations of relatively large effect often explain increased nectar volume and transition to red flower colour. In addition, they suggest that adaptive suites of floral traits may often exhibit a high degree of genetic linkage, which could facilitate their fixation during pollination syndrome evolution. Here, we explore these emerging generalities by investigating the genetic basis of floral pollination syndrome divergence between two related Penstemon species with different pollination syndromes--bee-pollinated P. neomexicanus and closely related hummingbird-pollinated P. barbatus. In an F2 mapping population derived from a cross between these two species, we characterized the effect size of genetic loci underlying floral trait divergence associated with the transition to bird pollination, as well as correlation structure of floral trait variation. We find the effect sizes of quantitative trait loci for adaptive floral traits are in line with patterns observed in previous studies, and find strong evidence that suites of floral traits are genetically linked. This linkage may be due to genetic proximity or pleiotropic effects of single causative loci. Interestingly, our data suggest that the evolution of floral traits critical for hummingbird pollination was not constrained by negative pleiotropy at loci that show co-localization for multiple traits.
| S-EPMC4071523 | biostudies-literature