Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination

Abstract Meiotic crossovers (COs) ensure proper chromosome segregation and redistribute the genetic variation that is transmitted to the next generation. Large populations and the demand for genome-wide, fine-scale resolution challenge existing methods for CO identification. Taking advantage of linked-read sequencing, we develop a highly efficient method for genome-wide identification of COs at kilobase resolution in pooled recombinants. We first test this method using a pool of Arabidopsis F2 recombinants, and recapitulate results obtained from the same plants using individual whole-genome sequencing. By applying this method to a pool of pollen DNA from an F1 plant, we establish a highly accurate CO landscape without generating or sequencing a single recombinant plant. The simplicity of this approach enables the simultaneous generation and analysis of multiple CO landscapes, accelerating the pace at which mechanisms for the regulation of recombination can be elucidated through efficient comparisons of genotypic and environmental effects on recombination.

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Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination

10.1101/484022 ◽

2018 ◽

Cited By ~ 2

Author(s):

Hequan Sun ◽

Beth A. Rowan ◽

Pádraic J. Flood ◽

Ronny Brandt ◽

Janina Fuss ◽

...

Keyword(s):

Genetic Variation ◽

Chromosome Segregation ◽

Meiotic Recombination ◽

Whole Genome ◽

Fine Scale ◽

Simultaneous Generation ◽

Genome Wide Analysis ◽

Recombinant Plant ◽

Genome Wide ◽

Large Populations

ABSTRACTMeiotic crossovers (COs) ensure proper chromosome segregation and redistribute the genetic variation that is transmitted to the next generation. Existing methods for CO identification are challenged by large populations and the demand for genome-wide and fine-scale resolution. Taking advantage of linked-read sequencing, we developed a highly efficient method for genome-wide identification of COs at kilobase resolution in pooled recombinants. We first tested this method using a pool of Arabidopsis F2 recombinants, and obtained results that recapitulated those identified from the same plants using individual whole-genome sequencing. By applying this method to a pool of pollen DNA from a single F1 plant, we established a highly accurate CO landscape without generating or sequencing a single recombinant plant. The simplicity of this approach now enables the simultaneous generation and analysis of multiple CO landscapes and thereby allows for efficient comparison of genotypic and environmental effects on recombination, accelerating the pace at which the mechanisms for the regulation of recombination can be elucidated.

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Genome-wide analysis of human hotspot intersected genes highlights the roles of meiotic recombination in evolution and disease

BMC Genomics ◽

10.1186/1471-2164-14-67 ◽

2013 ◽

Vol 14 (1) ◽

pp. 67 ◽

Cited By ~ 5

Author(s):

Tao Zhou ◽

Zhibin Hu ◽

Zuomin Zhou ◽

Xuejiang Guo ◽

Jiahao Sha

Keyword(s):

Meiotic Recombination ◽

Genome Wide Analysis ◽

Genome Wide

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Genetic Variability in Local and Imported Germplasm Chicken Populations as Revealed by Analyzing Runs of Homozygosity

Animals ◽

10.3390/ani10101887 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1887

Author(s):

Natalia V. Dementieva ◽

Andrei A. Kudinov ◽

Tatiana A. Larkina ◽

Olga V. Mitrofanova ◽

Artyom P. Dysin ◽

...

Keyword(s):

Genetic Variability ◽

Germplasm Collection ◽

Whole Genome ◽

Runs Of Homozygosity ◽

Breeding Programs ◽

Genome Wide Analysis ◽

Genome Wide ◽

Rare And Endangered ◽

Chicken Breeds ◽

Conservation Breeding

Preserving breed uniqueness and purity is vitally important in developing conservation/breeding programs for a germplasm collection of rare and endangered chicken breeds. The present study was aimed at analyzing SNP genetic variability of 21 small local and imported purebred and F1 crossbred populations and identifying crossbreeding events via whole-genome evaluation of runs of homozygosity (ROH). The admixture models more efficiently reflected population structure, pinpointing crossbreeding events in the presence of ancestral populations but not in their absence. Multidimensional scaling and FST-based analyses did not discriminate properly between purebred populations and F1 crossbreds, especially when comparing related breeds. When applying the ROH-based approach, more and longer ROHs were revealed in purebred individuals/populations, suggesting this as an effective implement in genome-wide analysis of germplasm breed purity.

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Genome-Wide Analysis of Soybean JmjC Domain-Containing Proteins Suggests Evolutionary Conservation Following Whole-Genome Duplication

Frontiers in Plant Science ◽

10.3389/fpls.2016.01800 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 10

Author(s):

Yapeng Han ◽

Xiangyong Li ◽

Lin Cheng ◽

Yanchun Liu ◽

Hui Wang ◽

...

Keyword(s):

Whole Genome Duplication ◽

Genome Duplication ◽

Evolutionary Conservation ◽

Whole Genome ◽

Genome Wide Analysis ◽

Genome Wide ◽

Jmjc Domain

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Genome-wide analysis of the expansin gene superfamily reveals Brassica rapa-specific evolutionary dynamics upon whole genome triplication

Molecular Genetics and Genomics ◽

10.1007/s00438-014-0935-0 ◽

2014 ◽

Vol 290 (2) ◽

pp. 521-530 ◽

Cited By ~ 17

Author(s):

Panneerselvam Krishnamurthy ◽

Joon Ki Hong ◽

Jin A Kim ◽

Mi-Jeong Jeong ◽

Yeon-Hee Lee ◽

...

Keyword(s):

Brassica Rapa ◽

Evolutionary Dynamics ◽

Whole Genome ◽

Genome Wide Analysis ◽

Expansin Gene ◽

Genome Wide ◽

Genome Triplication

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Induction of theCandida albicansFilamentous Growth Program by Relief of Transcriptional Repression: A Genome-wide Analysis

Molecular Biology of the Cell ◽

10.1091/mbc.e05-01-0073 ◽

2005 ◽

Vol 16 (6) ◽

pp. 2903-2912 ◽

Cited By ~ 207

Author(s):

David Kadosh ◽

Alexander D. Johnson

Keyword(s):

Candida Albicans ◽

Transcriptional Repression ◽

Fungal Pathogen ◽

Morphological Transition ◽

Whole Genome ◽

Transcriptional Repressors ◽

Genome Wide Analysis ◽

Human Fungal Pathogen ◽

Genome Wide ◽

A Genome

Candida albicans, the major human fungal pathogen, undergoes a reversible morphological transition from blastospores (round budding cells) to filaments (elongated cells attached end-to-end). This transition, which is induced upon exposure of C. albicans cells to a number of host conditions, including serum and body temperature (37°C), is required for virulence. Using whole-genome DNA microarray analysis, we describe 61 genes that are significantly induced (≥2-fold) during the blastospore to filament transition that takes place in response to exposure to serum and 37°C. We next show that approximately half of these genes are transcriptionally repressed in the blastospore state by three transcriptional repressors, Rfg1, Nrg1, and Tup1. We conclude that the relief of this transcriptional repression plays a key role in bringing the C. albicans filamentous growth program into play, and we describe the framework of this transcriptional circuit.

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Common genetic variation and survival after colorectal cancer diagnosis: a genome-wide analysis

Carcinogenesis ◽

10.1093/carcin/bgv161 ◽

2015 ◽

Vol 37 (1) ◽

pp. 87-95 ◽

Cited By ~ 18

Author(s):

Amanda I. Phipps ◽

Michael N. Passarelli ◽

Andrew T. Chan ◽

Tabitha A. Harrison ◽

Jihyoun Jeon ◽

...

Keyword(s):

Colorectal Cancer ◽

Genetic Variation ◽

Cancer Diagnosis ◽

Common Genetic Variation ◽

Genome Wide Analysis ◽

Genome Wide ◽

A Genome

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Whole-genome bisulfite sequencing in systemic sclerosis provides novel targets to understand disease pathogenesis

BMC Medical Genomics ◽

10.1186/s12920-019-0602-8 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Tianyuan Lu ◽

Kathleen Oros Klein ◽

Inés Colmegna ◽

Maximilien Lora ◽

Celia M. T. Greenwood ◽

...

Keyword(s):

Dna Methylation ◽

Genetic Variation ◽

Systemic Sclerosis ◽

Cytosine Methylation ◽

Bisulfite Sequencing ◽

Whole Genome ◽

Disease Pathogenesis ◽

Whole Genome Bisulfite Sequencing ◽

Genome Wide ◽

Genome Bisulfite Sequencing

Abstract Background Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease whose pathogenesis remains incompletely understood. Increasing evidence suggests that both genetic susceptibilities and changes in DNA methylation influence pivotal biological pathways and thereby contribute to the disease. The role of DNA methylation in SSc has not been fully elucidated, because existing investigations of DNA methylation predominantly focused on nucleotide CpGs within restricted genic regions, and were performed on samples containing mixed cell types. Methods We performed whole-genome bisulfite sequencing on purified CD4+ T lymphocytes from nine SSc patients and nine controls in a pilot study, and then profiled genome-wide cytosine methylation as well as genetic variations. We adopted robust statistical methods to identify differentially methylated genomic regions (DMRs). We then examined pathway enrichment associated with genes located in these DMRs. We also tested whether changes in CpG methylation were associated with adjacent genetic variation. Results We profiled DNA methylation at more than three million CpG dinucleotides genome-wide. We identified 599 DMRs associated with 340 genes, among which 54 genes exhibited further associations with adjacent genetic variation. We also found these genes were associated with pathways and functions that are known to be abnormal in SSc, including Wnt/β-catenin signaling pathway, skin lesion formation and progression, and angiogenesis. Conclusion The CD4+ T cell DNA cytosine methylation landscape in SSc involves crucial genes in disease pathogenesis. Some of the methylation patterns are also associated with genetic variation. These findings provide essential foundations for future studies of epigenetic regulation and genome-epigenome interaction in SSc.

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