scholarly journals Barcoded reciprocal hemizygosity analysis via sequencing illuminates the complex genetic basis of yeast thermotolerance

2021 ◽  
Author(s):  
Melanie B Abrams ◽  
Julie N Chuong ◽  
Faisal AlZaben ◽  
Claire A Dubin ◽  
Jeffrey M Skerker ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Genetic Dissection ◽  
Proof Of Concept ◽  
Mutagenesis Screen ◽  
Genetics Research ◽  
Multiple Loci ◽  
Genome Wide ◽  
The Difference ◽  
Candidate Loci ◽  
Reciprocal Hemizygosity Analysis

Abstract Decades of successes in statistical genetics have revealed the molecular underpinnings of traits as they vary across individuals of a given species. But standard methods in the field can’t be applied to divergences between reproductively isolated taxa. Genome-wide reciprocal hemizygosity mapping (RH-seq), a mutagenesis screen in an inter-species hybrid background, holds promise as a method to accelerate the progress of interspecies genetics research. Here we describe an improvement to RH-seq in which mutants harbor barcodes for cheap and straightforward sequencing after selection in a condition of interest. As a proof of concept for the new tool, we carried out genetic dissection of the difference in thermotolerance between two reproductively isolated budding yeast species. Experimental screening identified dozens of candidate loci at which variation between the species contributed to the thermotolerance trait. Hits were enriched for mitosis genes and other housekeeping factors, and among them were multiple loci with robust sequence signatures of positive selection. Together, these results shed new light on the mechanisms by which evolution solved the problems of cell survival and division at high temperature in the yeast clade, and they illustrate the power of the barcoded RH-seq approach.

scholarly journals Barcoded RH-seq illuminates the complex genetic basis of yeast thermotolerance

2021 ◽  
Author(s):  
Melanie B. Abrams ◽  
Julie N Chuong ◽  
Faisal AlZaben ◽  
Claire A. Dubin ◽  
Jeffrey M. Skerker ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Yeast Species ◽  
Genetic Dissection ◽  
Proof Of Concept ◽  
Species Hybrid ◽  
Mutagenesis Screen ◽  
Genetics Research ◽  
Multiple Loci ◽  
Genome Wide ◽  
The Difference

Decades of successes in statistical genetics have revealed the molecular underpinnings of traits as they vary across individuals of a given species. But standard methods in the field cant be applied to divergences between reproductively isolated taxa. Genome-wide reciprocal hemizygosity mapping (RH-seq), a mutagenesis screen in an inter-species hybrid background, holds promise as a method to accelerate the progress of interspecies genetics research. Toward this end we pioneered an improvement to RH-seq in which mutants harbor barcodes for cheap and straightforward phenotyping-by-sequencing. As a proof of concept for the new tool, we carried out genetic dissection of the difference in thermotolerance between two reproductively isolated budding yeast species. Experimental screening and sequencing identified dozens of loci at which variation between the species contributed to the thermotolerance trait. These hits were enriched for mitosis genes and other housekeeping factors, and among them were multiple loci with robust sequence signatures of positive selection. Together, our results shed new light on the mechanisms by which evolution solved the problems of cell survival and division at high temperature in the yeast clade, and they illustrate the power of the barcoded RH-seq approach.

scholarly journals Not just methods: User expertise explains the variability of outcomes of genome-wide studies

2016 ◽  
Author(s):  
Katie E. Lotterhos ◽  
Olivier François ◽  
Michael G.B. Blum
Keyword(s):  
Summer School ◽  
Statistical Power ◽  
A Priori ◽  
Simulated Data ◽  
Genome Scan ◽  
Genome Wide ◽  
The Difference ◽  
Difficult Challenge ◽  
Genomic Regions ◽  
Candidate Loci

AbstractGenome scan approaches promise to map genomic regions involved in adaptation of individuals to their environment. Outcomes of genome scans have been shown to depend on several factors including the underlying demography, the adaptive scenario, and the software or method used. We took advantage of a pedagogical experiment carried out during a summer school to explore the effect of an unexplored source of variability, which is the degree of user expertise.Participants were asked to analyze three simulated data challenges with methods presented during the summer school. In addition to submitting lists, participants evaluated a priori their level of expertise. We measured the quality of each genome scan analysis by computing a score that depends on false discovery rate and statistical power. In an easy and a difficult challenge, less advanced participants obtained similar scores compared to advanced ones, demonstrating that participants with little background in genome scan methods were able to learn how to use complex software after short introductory tutorials. However, in a challenge ofintermediate difficulty, advanced participants obtained better scores. To explain the difference, we introduce a probabilistic model that shows that a larger variation in scores is expected for SNPs of intermediate difficulty of detection. We conclude that practitioners should develop their statistical and computational expertise to follow the development of complex methods. To encourage training, we release the website of the summer school where users can submit lists of candidate loci, which will be scored and compared to the scores obtained by previous users.

scholarly journals Genetic Basis of Gluten Aggregation Properties in Wheat (Triticum aestivum L.) Dissected by QTL Mapping of GlutoPeak Parameters

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengfu Zhou ◽  
Ziwei Zhang ◽  
Lihua Jia ◽  
Hongxia Qiu ◽  
Huiyue Guan ◽  
...  
Keyword(s):  
Triticum Aestivum ◽  
Genetic Basis ◽  
Triticum Aestivum L ◽  
Interval Mapping ◽  
Wheat Breeding ◽  
Human Consumption ◽  
Processing Quality ◽  
Genome Wide ◽  
The Difference ◽  
Major Qtl

Bread wheat is one of the most important crops worldwide, supplying approximately one-fifth of the daily protein and the calories for human consumption. Gluten aggregation properties play important roles in determining the processing quality of wheat (Triticum aestivum L.) products. Nevertheless, the genetic basis of gluten aggregation properties has not been reported so far. In this study, a recombinant inbred line (RIL) population derived from the cross between Luozhen No. 1 and Zhengyumai 9987 was used to identify quantitative trait loci (QTL) underlying gluten aggregation properties with GlutoPeak parameters. A linkage map was constructed based on 8,518 SNPs genotyped by specific length amplified fragment sequencing (SLAF-seq). A total of 33 additive QTLs on 14 chromosomes were detected by genome-wide composite interval mapping (GCIM), four of which accounted for more than 10% of the phenotypic variation across three environments. Two major QTL clusters were identified on chromosomes 1DS and 1DL. A premature termination of codon (PTC) mutation in the candidate gene (TraesCS1D02G009900) of the QTL cluster on 1DS was detected between Luozhen No. 1 and Zhengyumai 9987, which might be responsible for the difference in gluten aggregation properties between the two varieties. Subsequently, two KASP markers were designed based on SNPs in stringent linkage with the two major QTL clusters. Results of this study provide new insights into the genetic architecture of gluten aggregation properties in wheat, which are helpful for future improvement of the processing quality in wheat breeding.

scholarly journals Comprehensive Genome-Wide Association Analysis Reveals the Genetic Basis of Root System Architecture in Soybean

2020 ◽  
Vol 11 ◽  
Author(s):  
Waldiodio Seck ◽  
Davoud Torkamaneh ◽  
François Belzile
Keyword(s):  
Root System ◽  
System Architecture ◽  
Phenotypic Variation ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Primary Root ◽  
Root System Architecture ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Genome Wide

Increasing the understanding genetic basis of the variability in root system architecture (RSA) is essential to improve resource-use efficiency in agriculture systems and to develop climate-resilient crop cultivars. Roots being underground, their direct observation and detailed characterization are challenging. Here, were characterized twelve RSA-related traits in a panel of 137 early maturing soybean lines (Canadian soybean core collection) using rhizoboxes and two-dimensional imaging. Significant phenotypic variation (P < 0.001) was observed among these lines for different RSA-related traits. This panel was genotyped with 2.18 million genome-wide single-nucleotide polymorphisms (SNPs) using a combination of genotyping-by-sequencing and whole-genome sequencing. A total of 10 quantitative trait locus (QTL) regions were detected for root total length and primary root diameter through a comprehensive genome-wide association study. These QTL regions explained from 15 to 25% of the phenotypic variation and contained two putative candidate genes with homology to genes previously reported to play a role in RSA in other species. These genes can serve to accelerate future efforts aimed to dissect genetic architecture of RSA and breed more resilient varieties.

scholarly journals Possibility of Human Gender Recognition Using Raman Spectra of Teeth

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3983
Author(s):  
Ozren Gamulin ◽  
Marko Škrabić ◽  
Kristina Serec ◽  
Matej Par ◽  
Marija Baković ◽  
...  
Keyword(s):  
Raman Spectra ◽  
Principal Component ◽  
Support Vector ◽  
Gender Recognition ◽  
Proof Of Concept ◽  
Male And Female ◽  
Tooth Type ◽  
Tooth Apex ◽  
The Difference

Gender determination of the human remains can be very challenging, especially in the case of incomplete ones. Herein, we report a proof-of-concept experiment where the possibility of gender recognition using Raman spectroscopy of teeth is investigated. Raman spectra were recorded from male and female molars and premolars on two distinct sites, tooth apex and anatomical neck. Recorded spectra were sorted into suitable datasets and initially analyzed with principal component analysis, which showed a distinction between spectra of male and female teeth. Then, reduced datasets with scores of the first 20 principal components were formed and two classification algorithms, support vector machine and artificial neural networks, were applied to form classification models for gender recognition. The obtained results showed that gender recognition with Raman spectra of teeth is possible but strongly depends both on the tooth type and spectrum recording site. The difference in classification accuracy between different tooth types and recording sites are discussed in terms of the molecular structure difference caused by the influence of masticatory loading or gender-dependent life events.

scholarly journals The Genetic Basis of Hypertriglyceridemia

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Germán D. Carrasquilla ◽  
Malene Revsbech Christiansen ◽  
Tuomas O. Kilpeläinen
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Cumulative Effect ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Risk Variants ◽  
Genome Wide ◽  
Severe Hypertriglyceridemia ◽  
Increased Risk ◽  
Polygenic Scores

Abstract Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.

scholarly journals Genome-Wide Analyses Identifies Known and New Markers Responsible of Chicken Plumage Color

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 493
Author(s):  
Salvatore Mastrangelo ◽  
Filippo Cendron ◽  
Gianluca Sottile ◽  
Giovanni Niero ◽  
Baldassare Portolano ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Snp Array ◽  
Fixation Index ◽  
Phenotypic Traits ◽  
Plumage Color ◽  
Phenotypic Marker ◽  
Genome Wide ◽  
A Genome ◽  
The Difference ◽  
Genomic Regions

Through the development of the high-throughput genotyping arrays, molecular markers and genes related to phenotypic traits have been identified in livestock species. In poultry, plumage color is an important qualitative trait that can be used as phenotypic marker for breed identification. In order to assess sources of genetic variation related to the Polverara chicken breed plumage colour (black vs. white), we carried out a genome-wide association study (GWAS) and a genome-wide fixation index (FST) scan to uncover the genomic regions involved. A total of 37 animals (17 white and 20 black) were genotyped with the Affymetrix 600 K Chicken single nucleotide polymorphism (SNP) Array. The combination of results from GWAS and FST revealed a total of 40 significant markers distributed on GGA 01, 03, 08, 12 and 21, and located within or near known genes. In addition to the well-known TYR, other candidate genes have been identified in this study, such as GRM5, RAB38 and NOTCH2. All these genes could explain the difference between the two Polverara breeds. Therefore, this study provides the basis for further investigation of the genetic mechanisms involved in plumage color in chicken.

A nonparametric test for association with multiple loci in the retrospective case-control study

2019 ◽  
Vol 29 (2) ◽  
pp. 589-602
Author(s):  
Chan Wang ◽  
Shufang Deng ◽  
Leiming Sun ◽  
Liming Li ◽  
Yue-Qing Hu
Keyword(s):  
Rare Variants ◽  
Association Studies ◽  
Nonparametric Test ◽  
Case Control ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Retrospective Case ◽  
Multiple Loci ◽  
Common Diseases ◽  
The Difference

The genome-wide association studies aim at identifying common or rare variants associated with common diseases and explaining more heritability. It is well known that common diseases are influenced by multiple single nucleotide polymorphisms (SNPs) that are usually correlated in location or function. In order to powerfully detect association signals, it is highly desirable to take account of correlations or linkage disequilibrium (LD) information among multiple SNPs in testing for association. In this article, we propose a test SLIDE that depicts the difference of the average multi-locus genotypes between cases and controls and derive its variance–covariance matrix in the retrospective design. This matrix is composed of the pairwise LD between SNPs. Thus SLIDE can borrow the strength from an external database in the population of interest with a few thousands to hundreds of thousands individuals to improve the power for detecting association. Extensive simulations show that SLIDE has apparent superiority over the existing methods, especially in the situation involving both common and rare variants, both protective and deleterious variants. Furthermore, the efficiency of the proposed method is demonstrated in the application to the data from the Wellcome Trust Case Control Consortium.

Sign in / Sign up

Export Citation Format

Share Document