scholarly journals The Theory and Applications of Measuring Broad-Range and Chromosome-Wide Recombination Rate from Allele Frequency Decay around a Selected Locus

2020 ◽  
Vol 37 (12) ◽  
pp. 3654-3671
Author(s):  
Kevin H -C Wei ◽  
Aditya Mantha ◽  
Doris Bachtrog
Keyword(s):  
Genetic Distance ◽  
Allele Frequency ◽  
Recombination Rate ◽  
High Throughput Sequencing ◽  
Genetic Material ◽  
Cost Effective ◽  
Genetic Distances ◽  
Recombination Rates ◽  
Marker Selection ◽  
Cost Effective Approach

Abstract Recombination is the exchange of genetic material between homologous chromosomes via physical crossovers. High-throughput sequencing approaches detect crossovers genome wide to produce recombination rate maps but are difficult to scale as they require large numbers of recombinants individually sequenced. We present a simple and scalable pooled-sequencing approach to experimentally infer near chromosome-wide recombination rates by taking advantage of non-Mendelian allele frequency generated from a fitness differential at a locus under selection. As more crossovers decouple the selected locus from distal loci, the distorted allele frequency attenuates distally toward Mendelian and can be used to estimate the genetic distance. Here, we use marker selection to generate distorted allele frequency and theoretically derive the mathematical relationships between allele frequency attenuation, genetic distance, and recombination rate in marker-selected pools. We implemented nonlinear curve-fitting methods that robustly estimate the allele frequency decay from batch sequencing of pooled individuals and derive chromosome-wide genetic distance and recombination rates. Empirically, we show that marker-selected pools closely recapitulate genetic distances inferred from scoring recombinants. Using this method, we generated novel recombination rate maps of three wild-derived strains of Drosophila melanogaster, which strongly correlate with previous measurements. Moreover, we show that this approach can be extended to estimate chromosome-wide crossover interference with reciprocal marker selection and discuss how it can be applied in the absence of visible markers. Altogether, we find that our method is a simple and cost-effective approach to generate chromosome-wide recombination rate maps requiring only one or two libraries.

scholarly journals The theory and practice of measuring broad-range recombination rate from marker selected pools

2019 ◽  
Author(s):  
Kevin H.-C. Wei ◽  
Aditya Mantha ◽  
Doris Bachtrog
Keyword(s):  
Genetic Distance ◽  
Allele Frequency ◽  
Recombination Rate ◽  
High Throughput Sequencing ◽  
Genetic Material ◽  
Cost Effective ◽  
Theory And Practice ◽  
Rate Variation ◽  
Sequencing Data ◽  
Genome Wide

ABSTRACTRecombination is the exchange of genetic material between homologous chromosomes via physical crossovers. Pioneered by T. H. Morgan and A. Sturtevant over a century ago, methods to estimate recombination rate and genetic distance require scoring large number of recombinant individuals between molecular or visible markers. While high throughput sequencing methods have allowed for genome wide crossover detection producing high resolution maps, such methods rely on large number of recombinants individually sequenced and are therefore difficult to scale. Here, we present a simple and scalable method to infer near chromosome-wide recombination rate from marker selected pools and the corresponding analytical software MarSuPial. Rather than genotyping individuals from recombinant backcrosses, we bulk sequence marker selected pools to infer the allele frequency decay around the selected locus; since the number of recombinant individuals increases proportionally to the genetic distance from the selected locus, the allele frequency across the chromosome can be used to estimate the genetic distance and recombination rate. We mathematically demonstrate the relationship between allele frequency attenuation, recombinant fraction, genetic distance, and recombination rate in marker selected pools. Based on available chromosome-wide recombination rate models of Drosophila, we simulated read counts and determined that nonlinear local regressions (LOESS) produce robust estimates despite the high noise inherent to sequencing data. To empirically validate this approach, we show that (single) marker selected pools closely recapitulate genetic distances inferred from scoring recombinants between double markers. We theoretically determine how secondary loci with viability impacts can modulate the allele frequency decay and how to account for such effects directly from the data. We generated the recombinant map of three wild derived strains which strongly correlates with previous genome-wide measurements. Interestingly, amidst extensive recombination rate variation, multiple regions of the genomes show elevated rates across all strains. Lastly, we apply this method to estimate chromosome-wide crossover interference. Altogether, we find that marker selected pools is a simple and cost effective method for broad recombination rate estimates. Although it does not identify instances of crossovers, it can generate near chromosome-wide recombination maps in as little as one or two libraries.

scholarly journals Role of cis, trans, and inbreeding effects on meiotic recombination in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Xavier Raffoux ◽  
Mickael Bourge ◽  
Fabrice Dumas ◽  
Olivier C. Martin ◽  
Matthieu Falque
Keyword(s):  
Saccharomyces Cerevisiae ◽  
High Throughput ◽  
Meiotic Recombination ◽  
Recombination Rate ◽  
Combining Ability ◽  
Sequence Similarity ◽  
Genetic Material ◽  
Recombination Rates ◽  
Important Species ◽  
High Throughput Method

ABSTRACTMeiotic recombination is a major driver of genome evolution by creating new genetic combinations. To probe the factors driving variability of meiotic recombination, we used a high-throughput method to measure recombination rates in 26 S. cerevisiae strains from different geographic origins and habitats. Fourteen intervals were monitored for each strain, covering chromosomes VI and XI entirely, and part of chromosome I. We found an average number of crossovers per chromosome ranging between 1.0 and 9.5 across strains (“domesticated” or not), which is higher than the average between 0.5 and 1.5 found in most organisms. In the different intervals analyzed, recombination showed up to 9-fold variation across strains but global recombination landscapes along chromosomes varied less. We also built an incomplete diallel experiment to measure recombination rates in one region of chromosome XI in 10 different crosses involving five parental strains. Our overall results indicate that recombination rate is increasingly positively correlated with sequence similarity between homologs (i) in DSB rich regions within intervals, (ii) in entire intervals, and (iii) at the whole genome scale. Therefore, these correlations cannot be explained by cis-effects only. In addition, by using a quantitative genetics analysis, we identified an inbreeding effect that reduces recombination rate in homozygous genotypes while other interaction effects (specific combining ability) or additive effects (general combining ability) are found to be weak. Finally, we measured significant crossover interference in some strains, and interference intensity was positively correlated with crossover number.Author SummaryMeiosis is a key process for sexually reproducing organisms by producing gametes with a halved set of genetic material. An essential step of meiosis is the formation of crossovers which are reciprocal exchanges of genetic material between chromosomes inherited from both parents. Crossovers ensure proper chromosome segregation and thus viable gametes. They also create novel genetic diversity which contributes to evolution and permits genetic improvement of agriculturally important species. Most living organisms produce between one and three crossovers per chromosome, and tight regulatory mechanisms control the number of crossovers and their distribution along chromosomes. In spite of their potential importance for biotechnological applications, such mechanisms are still poorly understood.Using a high throughput method based on fluorescent markers, we investigated the diversity of recombination in the budding yeast Saccharomyces cerevisiae. We observed up to 9-fold differences in numbers of crossovers across hybrids obtained by crossing different strains with a common tester, and this variation was correlated with the degree of DNA sequence similarity between homologous chromosomes. By also investigating homozygotes, we conclude that on the one hand too much sequence divergence impairs recombination in distantly-related hybrids, and on the other hand complete homozygosity is also associated with lower numbers of crossovers.

scholarly journals One is not enough: On the effects of reference genome for the mapping and subsequent analyses of short-reads

2021 ◽  
Vol 17 (1) ◽  
pp. e1008678
Author(s):  
Carlos Valiente-Mullor ◽  
Beatriz Beamud ◽  
Iván Ansari ◽  
Carlos Francés-Cuesta ◽  
Neris García-González ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Phylogenetic Trees ◽  
High Throughput Sequencing ◽  
Reference Genome ◽  
Sequence Data ◽  
Genetic Distances ◽  
Genomic Diversity ◽  
Nucleotide Polymorphisms ◽  
Recombination Rates ◽  
Almost All

Mapping of high-throughput sequencing (HTS) reads to a single arbitrary reference genome is a frequently used approach in microbial genomics. However, the choice of a reference may represent a source of errors that may affect subsequent analyses such as the detection of single nucleotide polymorphisms (SNPs) and phylogenetic inference. In this work, we evaluated the effect of reference choice on short-read sequence data from five clinically and epidemiologically relevant bacteria (Klebsiella pneumoniae, Legionella pneumophila, Neisseria gonorrhoeae, Pseudomonas aeruginosa and Serratia marcescens). Publicly available whole-genome assemblies encompassing the genomic diversity of these species were selected as reference sequences, and read alignment statistics, SNP calling, recombination rates, dN/dS ratios, and phylogenetic trees were evaluated depending on the mapping reference. The choice of different reference genomes proved to have an impact on almost all the parameters considered in the five species. In addition, these biases had potential epidemiological implications such as including/excluding isolates of particular clades and the estimation of genetic distances. These findings suggest that the single reference approach might introduce systematic errors during mapping that affect subsequent analyses, particularly for data sets with isolates from genetically diverse backgrounds. In any case, exploring the effects of different references on the final conclusions is highly recommended.

scholarly journals Cross-Species Application of Illumina iScan Microarrays for Cost-Effective, High-Throughput SNP Discovery

2021 ◽  
Vol 9 ◽  
Author(s):  
Emily D. Fountain ◽  
Li-Chen Zhou ◽  
Alyssa Karklus ◽  
Qun-Xiu Liu ◽  
James Meyers ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Cost Effective ◽  
Model Organisms ◽  
Nucleotide Polymorphisms ◽  
Snp Discovery ◽  
Cost Effective Approach ◽  
Proprietary Format ◽  
Custom Script ◽  
Existing Data

Microarrays can be a cost-effective alternative to high-throughput sequencing for discovering novel single-nucleotide polymorphisms (SNPs). Illumina’s iScan platform dominates the market, but their commercial microarray products are designed for model organisms. Further, the platform outputs data in a proprietary format. This cannot be easily converted to human-readable genotypes or be merged with pre-existing data. To address this, we present and validate a novel pipeline to facilitate data analysis from cross-species application of Illumina microarrays. This facilitates the generation of a compatible VCF from iScan data and the merging of this with a second VCF comprising genotypes derived from other samples and sources. Our pipeline includes a custom script, iScanVCFMerge (presented as a Python package), which we validate using iScan data from three great ape genera. We conclude that cross-species application of microarrays can be a rapid, cost-effective approach for SNP discovery in non-model organisms. Our pipeline surmounts the common challenges of integrating iScan genotypes with pre-existing data.

scholarly journals Recombination Pattern Characterization via Simulation Using Different Maize Populations

2020 ◽  
Vol 21 (6) ◽  
pp. 2222
Author(s):  
Wei Ren ◽  
Xiaoping Gong ◽  
Kun Li ◽  
Hongwei Zhang ◽  
Fanjun Chen ◽  
...  
Keyword(s):  
Recombination Rate ◽  
Cost Effective ◽  
Simulation Method ◽  
Construction Process ◽  
Effective Population ◽  
Recombination Rates ◽  
Crop Species ◽  
Different Types ◽  
Optimal Recombination ◽  
Almost All

Efficient recombination is critical to both plant breeding and gene cloning. However, almost all traditional recombination studies and genetic improvements require the slow and labor-intensive population construction process, and little is known about the recombination characteristics of populations of different types, generations, and origins. Here, we provide a simple and efficient simulation method for population construction based on doubled haploid (DH) and intermated B73 × Mo17 maize (IBM) populations to predict the recombination pattern. We found that the chromosomes had 0, 1, 2, and 3 recombination events that occurred at rates of 0.16, 0.30, 0.23, and 0.15, respectively, in the DH and the recombination rate of each chromosome in the IBM population ranged from 0 to 12.1 cM per 125 kb. Based on the observed recombination parameters, we estimated the number of recombination events and constructed the linkage maps of the simulated DH and recombination inbred line (RIL) populations. These simulated populations exhibited similar recombination patterns compared with the real populations, suggesting the feasibility of this simulation approach. We then compared the recombination rates of the simulated populations of different types (DH induced or self-crossed), generations, and origins (using the 8, 16, and 32 multiparent advanced generation intercross (MAGIC) populations), and suggested a rapid and cost-effective population construction procedure for breeders and geneticists, while maintaining an optimal recombination rate. This study offers a convenient method for optimizing the population construction process and has broader implications for other crop species, thereby facilitating future population studies and genetic improvement strategies.

E-Insurance :A Platform For Insurance Penetration In India

2019 ◽  
Vol 118 (6) ◽  
pp. 90-93
Author(s):  
L. Terina Grazy ◽  
Dr.G. Parimalarani
Keyword(s):  
Insurance Industry ◽  
Cost Effective ◽  
Online Marketing ◽  
Insurance Companies ◽  
The Internet ◽  
Insurance Sector ◽  
The People ◽  
Cost Effective Approach ◽  
Time And Energy ◽  
Work Done

E-commerce is a part of Internet Marketing. The arrival of Internet made the world very simple and dynamic in all the areas. Internet is the growing business as a result most of the people are using it in their day to day life. E-commerce is attractive and efficient way for both buyers and sellesr as it reduce cost, time and energy for the buyer. No surprise the insurance sector has become quite active within the internet sphere. Most insurance companies are offering policies to be brought online and also the portals for paying premiums. It actually saves from hassles involved in going to an insurance office and spend hours to get the insurance work done. Insurance has become an important and crucial aspect of life. Online insurance is the best and most cost effective approach of taking the insurance deal. This paper focused on influence of online marketing on the insurance industry in India, usage of internet in India , the internet penetration in India and the online sale of insurance product by the insurance sector.

Conclusion

2018 ◽  
Author(s):  
Yana van der Meulen Rodgers
Keyword(s):  
Family Planning ◽  
Reproductive Health ◽  
Health Services ◽  
Health Outcomes ◽  
Cost Effective ◽  
Reproductive Health Services ◽  
Cost Effective Approach ◽  
Restrictive Legislation

Chapter 7 concludes by highlighting the three biggest messages from the analysis presented in this book: (1) the global gag rule has failed to achieve its goal of reducing abortions; (2) restrictive legislation is associated with more unsafe abortions; and (3) the expanded global gag rule is likely to have negative repercussions across a range of health outcomes for women, children, and men. They are simple but powerful messages that should be heard by policymakers over the voices calling for an ideologically based policy that fails to achieve its desired outcome. The chapter closes with a more constructive and cost-effective approach for US family-planning assistance that targets integrated reproductive health services.

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