scholarly journals Detecting gene subnetworks under selection in biological pathways

2017 ◽  
Author(s):  
Alexandre Gouy ◽  
Joséphine T. Daub ◽  
Laurent Excoffier
Keyword(s):  
Complex Traits ◽  
Gene Networks ◽  
High Throughput Sequencing ◽  
Biological Pathways ◽  
General Idea ◽  
Human Populations ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Evolutionary Features ◽  
Gene Network Analysis

ABSTRACTAdvances in high throughput sequencing technologies have created a gap between data production and functional data analysis. Indeed, phenotypes result from interactions between numerous genes, but traditional methods treat loci independently, missing important knowledge brought by network-level emerging properties. Therefore, evidencing selection acting on multiple genes affecting the evolution of complex traits remains challenging. In this context, gene network analysis provides a powerful framework to study the evolution of adaptive traits and facilitates the interpretation of genome-wide data. To tackle this problem, we developed a method to analyse gene networks that is suitable to evidence polygenic selection. The general idea is to search biological pathways for subnetworks of genes that directly interact with each other and that present unusual evolutionary features. Subnetwork search is a typical combinatorial optimization problem that we solve using a simulated annealing approach. We have applied our methodology to find signals of adaptation to high-altitude in human populations. We show that this adaptation has a clear polygenic basis and is influenced by many genetic components. Our approach improves on classical tests for selection based on single genes by identifying both new candidate genes and new biological processes involved in adaptation to altitude.

scholarly journals Sequence and Evolutionary Features for the Alternatively Spliced Exons of Eukaryotic Genes

2019 ◽  
Vol 20 (15) ◽  
pp. 3834 ◽  
Author(s):  
Shi-Yi Chen ◽  
Cao Li ◽  
Xianbo Jia ◽  
Song-Jia Lai
Keyword(s):  
Alternative Splicing ◽  
High Throughput Sequencing ◽  
Point Of View ◽  
Sequencing Technologies ◽  
Eukaryotic Genes ◽  
Splicing Pattern ◽  
Evolutionary Features ◽  
Alternatively Spliced ◽  
Alternative Splicing Events ◽  
Alternatively Spliced Exons

Alternative splicing of pre-mRNAs is a crucial mechanism for maintaining protein diversity in eukaryotes without requiring a considerable increase of genes in the number. Due to rapid advances in high-throughput sequencing technologies and computational algorithms, it is anticipated that alternative splicing events will be more intensively studied to address different kinds of biological questions. The occurrences of alternative splicing mean that all exons could be classified to be either constitutively or alternatively spliced depending on whether they are virtually included into all mature mRNAs. From an evolutionary point of view, therefore, the alternatively spliced exons would have been associated with distinctive biological characteristics in comparison with constitutively spliced exons. In this paper, we first outline the representative types of alternative splicing events and exon classification, and then review sequence and evolutionary features for the alternatively spliced exons. The main purpose is to facilitate understanding of the biological implications of alternative splicing in eukaryotes. This knowledge is also helpful to establish computational approaches for predicting the splicing pattern of exons.

Genomic resources for improving food legume crops

2011 ◽  
Vol 150 (3) ◽  
pp. 289-318 ◽  
Author(s):  
J. KUMAR ◽  
A. PRATAP ◽  
R. K. SOLANKI ◽  
D. S. GUPTA ◽  
A. GOYAL ◽  
...  
Keyword(s):  
Complex Traits ◽  
Genetic Improvement ◽  
High Throughput Sequencing ◽  
Artificial Chromosome ◽  
Interactive Effects ◽  
Genetic Dissection ◽  
Genomic Resources ◽  
Sequencing Technologies ◽  
Food Legumes ◽  
Genomic Regions

SUMMARYFood legumes are the main source of dietary protein for a large part of the world's population, and also play an important role in maintaining soil fertility through nitrogen fixation. However, legume yields and production are often limited by large genotype×environment (G×E) interactions that influence the expression of agronomically important, complex quantitative traits. Consequently, genetic improvement has been slower than expected. Molecular marker technology enables genetic dissection of such complex traits, allowing breeders to identify genomic regions on the chromosome that have main effects or interactive effects. A number of genomic resources have been developed in several legume species during the last two decades, and provide a platform for exploiting marker technology. The present paper reviews the available genomic resources in food legumes: linkage maps, high-throughput sequencing technologies, expression sequence tag (EST) databases, genome sequences, DNA chips, targeting induced local lesions in genomes (TILLING), bacterial artificial chromosome (BAC) libraries and others. It also describes how these resources are being used to tag and map genes/quantitative trait loci (QTLs) for domesticated and other agronomically important traits. This information is important to genetic improvement efforts aiming at improving food and nutrition security worldwide.

scholarly journals Pair-wise Comparison Analysis for Multiple Pool-seq: an efficient method identified anthocyanin biosynthesis genes in rice pericarp

2019 ◽  
Author(s):  
Xinghai Yang ◽  
Xiuzhong Xia ◽  
Zongqiong Zhang ◽  
Baoxuan Nong ◽  
Yu Zeng ◽  
...  
Keyword(s):  
Efficient Method ◽  
Complex Traits ◽  
High Throughput Sequencing ◽  
Anthocyanin Biosynthesis ◽  
Comparison Analysis ◽  
Sequencing Technologies ◽  
Filial Generation ◽  
Genomic Regions ◽  
Pair Wise Comparison ◽  
New Strategies

AbstractThe complex traits are derived from multiple genes and exhibit a large variety of phenotypes. High-throughput sequencing technologies have become the new strategies for mapping the important traits of crops. However, these methods have their own disadvantages and limitations. Here we introduced Pair-wise Comparison Analysis for Multiple Pool-seq (PCAMP) for mapping the candidate genomic regions involved in anthocyanin biosynthesis in rice pericarp. In this protocol, the second filial generation (F2) populations obtained by crossing two parents with different target traits were divided into n (n>=3) subpopulations according to their phenotypes. Thirty phenotypically identical individuals were selected from each subpopulation and DNA samples were extracted to form a pool for sequencing. Finally, we compared the SNP-index between every two Pool-seqs to map the candidate genomic regions. We applied PCAMP to analyse F2 populations and successfully identified five known genes and five new candidate genomic regions for anthocyanin biosynthesis in rice pericarp. These results demonstrate that PCAMP is an efficient new method for dissecting the complex traits of crops.

scholarly journals The genomic landscape of polymorphic human nuclear mitochondrial insertions

2014 ◽  
Author(s):  
Gargi Dayama ◽  
Sarah B Emery ◽  
Jeffrey M Kidd ◽  
Ryan E Mills
Keyword(s):  
High Throughput Sequencing ◽  
Reference Genome ◽  
Current Knowledge ◽  
Genetic Material ◽  
Purifying Selection ◽  
Genomic Variation ◽  
Human Populations ◽  
Sequencing Data ◽  
Sequencing Technologies ◽  
D Loop

The transfer of mitochondrial genetic material into the nuclear genomes of eukaryotes is a well-established phenomenon. Many studies over the past decade have utilized reference genome sequences of numerous species to characterize the prevalence and contribution of nuclear mitochondrial insertions to human diseases. The recent advancement of high throughput sequencing technologies has enabled the interrogation of genomic variation at a much finer scale, and now allows for an exploration into the diversity of polymorphic nuclear mitochondrial insertions (NumtS) in human populations. We have developed an approach to discover and genotype previously undiscovered Numt insertions using whole genome, paired-end sequencing data. We have applied this method to almost a thousand individuals in twenty populations from the 1000 Genomes Project and other data sets and identified 138 novel sites of Numt insertions, extending our current knowledge of existing Numt locations in the human genome by almost 20%. Most of the newly identified NumtS were found in less than 1% of the samples we examined, suggesting that they occur infrequently in nature or have been rapidly removed by purifying selection. We find that recent Numt insertions are derived from throughout the mitochondrial genome, including the D-loop, and have integration biases consistent with previous studies on older, fixed NumtS in the reference genome. We have further determined the complete inserted sequence for a subset of these events to define their age and origin of insertion as well as their potential impact on studies of mitochondrial heteroplasmy.

Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Sharifa Hasana ◽  
Md. Farhad Hossain ◽  
Md. Siddiqul Islam ◽  
Tapan Behl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Massively Parallel Sequencing ◽  
Late Onset ◽  
Current Knowledge ◽  
The Elderly ◽  
Apoe Ε4 ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

A Primer of Population Genetics and Genomics

2020 ◽  
Author(s):  
Daniel L. Hartl
Keyword(s):  
Population Genetics ◽  
Complex Traits ◽  
Evolutionary Biology ◽  
Knowledge Retention ◽  
Learning By Doing ◽  
Human Populations ◽  
Gene Drive ◽  
Molecular Population Genetics ◽  
Genetics And Genomics ◽  
And Mathematics

A Primer of Population Genetics and Genomics, 4th edition, has been completely revised and updated to provide a concise but comprehensive introduction to the basic concepts of population genetics and genomics. Recent textbooks have tended to focus on such specialized topics as the coalescent, molecular evolution, human population genetics, or genomics. This primer bucks that trend by encouraging a broader familiarity with, and understanding of, population genetics and genomics as a whole. The overview ranges from mating systems through the causes of evolution, molecular population genetics, and the genomics of complex traits. Interwoven are discussions of ancient DNA, gene drive, landscape genetics, identifying risk factors for complex diseases, the genomics of adaptation and speciation, and other active areas of research. The principles are illuminated by numerous examples from a wide variety of animals, plants, microbes, and human populations. The approach also emphasizes learning by doing, which in this case means solving numerical or conceptual problems. The rationale behind this is that the use of concepts in problem-solving lead to deeper understanding and longer knowledge retention. This accessible, introductory textbook is aimed principally at students of various levels and abilities (from senior undergraduate to postgraduate) as well as practising scientists in the fields of population genetics, ecology, evolutionary biology, computational biology, bioinformatics, biostatistics, physics, and mathematics.

scholarly journals Reassortment of Genome Segments Creates Stable Lineages Among Strains of Orchid Fleck Virus Infecting Citrus in Mexico

2020 ◽  
Vol 110 (1) ◽  
pp. 106-120 ◽  
Author(s):  
Avijit Roy ◽  
Andrew L. Stone ◽  
Gabriel Otero-Colina ◽  
Gang Wei ◽  
Ronald H. Brlansky ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Sensu Stricto ◽  
Genome Segment ◽  
Rt Pcr ◽  
Sequence Comparisons ◽  
Orchid Fleck Virus ◽  
Reverse Transcription Pcr ◽  
Sequencing Technologies ◽  
Negative Sense

The genus Dichorhavirus contains viruses with bipartite, negative-sense, single-stranded RNA genomes that are transmitted by flat mites to hosts that include orchids, coffee, the genus Clerodendrum, and citrus. A dichorhavirus infecting citrus in Mexico is classified as a citrus strain of orchid fleck virus (OFV-Cit). We previously used RNA sequencing technologies on OFV-Cit samples from Mexico to develop an OFV-Cit–specific reverse transcription PCR (RT-PCR) assay. During assay validation, OFV-Cit–specific RT-PCR failed to produce an amplicon from some samples with clear symptoms of OFV-Cit. Characterization of this virus revealed that dichorhavirus-like particles were found in the nucleus. High-throughput sequencing of small RNAs from these citrus plants revealed a novel citrus strain of OFV, OFV-Cit2. Sequence comparisons with known orchid and citrus strains of OFV showed variation in the protein products encoded by genome segment 1 (RNA1). Strains of OFV clustered together based on host of origin, whether orchid or citrus, and were clearly separated from other dichorhaviruses described from infected citrus in Brazil. The variation in RNA1 between the original (now OFV-Cit1) and the new (OFV-Cit2) strain was not observed with genome segment 2 (RNA2), but instead, a common RNA2 molecule was shared among strains of OFV-Cit1 and -Cit2, a situation strikingly similar to OFV infecting orchids. We also collected mites at the affected groves, identified them as Brevipalpus californicus sensu stricto, and confirmed that they were infected by OFV-Cit1 or with both OFV-Cit1 and -Cit2. OFV-Cit1 and -Cit2 have coexisted at the same site in Toliman, Queretaro, Mexico since 2012. OFV strain-specific diagnostic tests were developed.

scholarly journals Application of Oxford Nanopore Technology to Plant Virus Detection

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1424
Author(s):  
Lia W. Liefting ◽  
David W. Waite ◽  
Jeremy R. Thompson
Keyword(s):  
Plant Virus ◽  
High Throughput Sequencing ◽  
Virus Detection ◽  
Diagnostic Methods ◽  
Plant Virus Detection ◽  
Sequencing Technologies ◽  
Oxford Nanopore ◽  
Virus Diagnostics ◽  
Post Entry ◽  
Read Accuracy

The adoption of Oxford Nanopore Technologies (ONT) sequencing as a tool in plant virology has been relatively slow despite its promise in more recent years to yield large quantities of long nucleotide sequences in real time without the need for prior amplification. The portability of the MinION and Flongle platforms combined with lowering costs and continued improvements in read accuracy make ONT an attractive method for both low- and high-scale virus diagnostics. Here, we provide a detailed step-by-step protocol using the ONT Flongle platform that we have developed for the routine application on a range of symptomatic post-entry quarantine and domestic surveillance plant samples. The aim of this methods paper is to highlight ONT’s feasibility as a valuable component to the diagnostician’s toolkit and to hopefully stimulate other laboratories towards the eventual goal of integrating high-throughput sequencing technologies as validated plant virus diagnostic methods in their own right.

scholarly journals Assessing genotyping errors in mammalian museum study skins using high-throughput genotyping-by-sequencing

2021 ◽  
Author(s):  
Stella C. Yuan ◽  
Eric Malekos ◽  
Melissa T. R. Hawkins
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Massively Parallel Sequencing ◽  
Massively Parallel ◽  
Museum Specimens ◽  
Museum Specimen ◽  
Genotyping Errors ◽  
Allelic Dropout ◽  
Parallel Sequencing ◽  
Sequencing Technologies

AbstractThe use of museum specimens held in natural history repositories for population and conservation genetic research is increasing in tandem with the use of massively parallel sequencing technologies. Short Tandem Repeats (STRs), or microsatellite loci, are commonly used genetic markers in wildlife and population genetic studies. However, they traditionally suffered from a host of issues including length homoplasy, high costs, low throughput, and difficulties in reproducibility across laboratories. Massively parallel sequencing technologies can address these problems, but the incorporation of museum specimen derived DNA suffers from significant fragmentation and exogenous DNA contamination. Combatting these issues requires extra measures of stringency in the lab and during data analysis, yet there have not been any high-throughput sequencing studies evaluating microsatellite allelic dropout from museum specimen extracted DNA. In this study, we evaluate genotyping errors derived from mammalian museum skin DNA extracts for previously characterized microsatellites across PCR replicates utilizing high-throughput sequencing. We found it useful to classify samples based on DNA concentration, which determined the rate by which genotypes were accurately recovered. Longer microsatellites performed worse in all museum specimens. Allelic dropout rates across loci were dependent on sample quantity, with high concentration museum specimens performing as well and recovering quality metrics nearly as high as the frozen tissue sample. Based on our results, we provide a set of best practices for quality assurance and incorporation of reliable genotypes from museum specimens.

scholarly journals Multi-omics approach to precision medicine for immune-mediated diseases

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Mineto Ota ◽  
Keishi Fujio
Keyword(s):  
Treatment Response ◽  
High Throughput Sequencing ◽  
Disease Risk ◽  
Clinical Information ◽  
Clinical Settings ◽  
Social Significance ◽  
Sequencing Technologies ◽  
Immune Mediated ◽  
Recent Innovation ◽  
Future Direction

AbstractRecent innovation in high-throughput sequencing technologies has drastically empowered the scientific research. Consequently, now, it is possible to capture comprehensive profiles of samples at multiple levels including genome, epigenome, and transcriptome at a time. Applying these kinds of rich information to clinical settings is of great social significance. For some traits such as cardiovascular diseases, attempts to apply omics datasets in clinical practice for the prediction of the disease risk have already shown promising results, although still under way for immune-mediated diseases. Multiple studies have tried to predict treatment response in immune-mediated diseases using genomic, transcriptomic, or clinical information, showing various possible indicators. For better prediction of treatment response or disease outcome in immune-mediated diseases, combining multi-layer information together may increase the power. In addition, in order to efficiently pick up meaningful information from the massive data, high-quality annotation of genomic functions is also crucial. In this review, we discuss the achievement so far and the future direction of multi-omics approach to immune-mediated diseases.

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