Structural variant calling: the long and the short of it

Mahmoud, Medhat; Gobet, Nastassia; Cruz-Dávalos, Diana Ivette; Mounier, Ninon; Dessimoz, Christophe; Sedlazeck, Fritz J.

doi:10.1186/s13059-019-1828-7

Cited by 465 publications

(438 citation statements)

References 105 publications

Supporting

Mentioning

423

Contrasting

Unclassified

Order By: Relevance

“…Structural variants (SVs) are genomic rearrangements affecting the presence, position or direction of a nucleotide sequence, including deletions, duplications, insertions, inversion or translocations (Mahmoud et al, 2019). SVs are pervasive variants that shape genome architecture and they can cover a larger proportion of genetic variation than SNPs (Redon et al, 2006;Wellenreuther et al, 2019;Catanach et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Dorant

Cayuela

Wellband

et al. 2020

Preprint

View full text Add to dashboard Cite

Copy number variants (CNVs) are a major component of genotypic and phenotypic variation in genomes. Yet, our knowledge on genotypic variation and evolution is often limited to single nucleotide polymorphism (SNPs) and the role of CNVs has been overlooked in non-model species, partly due to their challenging identification until recently. Here, we document the usefulness of reducedrepresentation sequencing data (RAD-seq) to detect and investigate copy number variants (CNVs) alongside SNPs in American lobster (Homarus americanus) populations. We conducted a comparative study to examine the potential role of SNPs and CNVs in local adaptation by sequencing 1141 lobsters from 21 sampling sites within the southern Gulf of St. Lawrence which experiences the highest yearly thermal variance of the Canadian marine coastal waters. Our results demonstrated that CNVs accounts for higher genetic differentiation than SNP markers. Contrary to SNPs for which no association was found, genetic-environment association revealed that 48 CNV candidates were significantly associated with the annual variance of sea surface temperature, leading to the genetic clustering of sampling locations despite their geographic separation. Altogether, we provide a strong empirical case that CNVs putatively contribute to local adaptation in marine species and unveil stronger spatial signal than SNPs.Our study provides the means to study CNVs in non-model species and underlines the importance to consider structural variants alongside SNPs to enhance our understanding of ecological and evolutionary processes shaping adaptive population structure.

show abstract

Section: Introductionmentioning

confidence: 99%

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Dorant

Cayuela

Wellband

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The different SV datasets clearly have different advantages and disadvantages. For example, genome alignments can be poor for detecting heterozygous SVs, because primary assemblies ignore alternative haplotypes (66); they tend to be best at identifying large SV events, such as large insertions (67). In contrast, SMRTread mapping should be efficient for most SV detection, outperforming short-read data (58,68).…”

Section: Svs Across Datasetsmentioning

confidence: 99%

Evolutionary genomics of structural variation in Asian rice (Oryza sativa) and its wild progenitor (O. rufipogon)

Kou

Liao

Toivainen

et al. 2019

Preprint

View full text Add to dashboard Cite

Structural variants (SVs) are a largely unstudied feature of plant genome evolution, despite the fact that SVs contribute substantially to phenotypes. In this study, we discovered structural variants (SVs) across a population sample of 358 high-coverage, resequenced genomes of Asian rice (Oryza sativa) and its wild ancestor (O. rufipogon). In addition to this short-read dataset, we also inferred SVs from whole-genome assemblies and long-read data. Comparisons among datasets revealed different features of genome variability. For example, genome alignment identified a large (~4.3 Mb) inversion in indica rice varieties relative to an outgroup, and longread analyses suggest that ~9% of genes from this outgroup are hemizygous. We focused, however, on the resequencing sample to investigate the population genomics of SVs. Clustering analyses with SVs recapitulated the rice cultivar groups that were also inferred from SNPs.However, the site-frequency spectrum of each SV type --which included inversions, duplications, deletions, translocations and mobile element insertions --was skewed toward lower frequency variants than synonymous SNPs, suggesting that SVs are predominantly deleterious. The strength of these deleterious effects varied among SV types, with inversions especially deleterious, and across transposable element (TE) families. Among TEs SINE and mariner insertions were especially deleterious, due to stronger selection against their insertions. We also used SVs to study domestication by contrasting between rice and O. rufipogon. Cultivated genomes contained ~25% more derived SVs than O. rufipogon, suggesting these deleterious SVs contribute to the cost of domestication. We also used SVs to study the effects of positive selection on the rice genome. Generally, the search for domestication genes were enriched for known candidates, suggesting some utility for SVs towards this purpose. More importantly, we detected hundreds to thousands of genes gained and lost during domestication, many of which are predicted to contribute to traits of agronomic interest.

show abstract

“…Around half of all detected, high-confidence SV events 115 (46.8 to 53.2 % across the 12 genotypes) ranged in size from ~100-1000 bp ( Supplementary 116 Table S2). These small SV represent a novel genetic diversity resource that was previously 117 unnoticed due to the insufficient resolution of high-throughput genotyping platforms such as 118 SNP genotyping arrays and a very high false-positive rates (up to 89%) of short-read 119 sequencing data (Mahmoud et al, 2019;Sedlazeck et al, 2018). 120…”

Section: Introduction 43mentioning

confidence: 99%

Long-read sequencing reveals widespread intragenic structural variants in a recent allopolyploid crop plant

Chawla

Lee

Gabur

et al. 2020

Preprint

View full text Add to dashboard Cite

Phone: +49 641 9937420 20 21 22 highly-duplicated nature of plant genomes, which makes them difficult to assess using high-31throughput genome screening methods. Here we describe how long-read sequencing 32 technologies can overcome this problem, revealing a surprisingly high level of widespread, 33 small to mid-scale SV in a major allopolyploid crop species, Brassica napus. We found that 34 up to 10% of all genes were affected by small to mid-scale SV events. Nearly half of these 35 SV events ranged between 100 bp to 1000 bp, which makes them challenging to detect using 36 short read Illumina sequencing. Examples demonstrating the contribution of such SV towards 37 eco-geographical adaptation and disease resistance in oilseed rape suggest that revisiting 38 complex plant genomes using medium-coverage, long-read sequencing might reveal 39 unexpected levels of functional gene variation, with major implications for trait regulation 40 and crop improvement. 41 visualization based on mRNAseq data (He et al., 2017) or deletion calling from SNP array 55 data (Gabur et al., 2018;Grandke et al., 2016). Critically, numerous examples have 56 connected genome SV in B. napus to important agronomic traits (Gabur et al., 2018; Gabur et 57 al., 2019;Liu et al., 2012;Stein et al., 2017). These studies revealed the important role of SV 58 in the creation of de novo variation for adaptation and breeding, however the methods used 59were not yet capable of resolving SV at gene scale. 60 A first example of intragenic SV impacting quantitatively inherited traits in B. napus was 61 reported by Qian et al. (2016), who demonstrated that deletion of exons 2 and 3 from a B. 62 napus orthologue of Mendel's "Green Cotyledon" gene (the Staygreen gene NON-63 YELLOWING 1; NYE1) associated with quantitative variation for chlorophyll and oil content. 64 Unfortunately, such small deletions are challenging to reliably detect using short-read 65 sequencing or low-cost marker arrays, so that their genome-wide extent could not yet be 66 investigated in detail. In this study, using B. napus as an example for a plant genome with 67 widespread structural variation, we demonstrate the power of whole-genome long-read 68 sequencing for high-resolution detection of intragenic SV. The results reveal widespread 69 functional variation on a completely unexpected scale, suggesting that small to mid-scale SV 70 may be a major driver of functional gene diversity in this recent polyploid crop. With the 71 growing accessibility, accuracy and cost-effectiveness of long-read sequencing, our results 72 suggest that there could be enormous promise in revisiting complex crop genomes to discover 73 potentially novel functional SV which has previously been overlooked. 74 75 Results and discussions 76 Long read sequencing reveal novel SV diversity in B. napus 77 We sequenced 4 B. napus accessions with long reads using the Oxford Nanopore Technology 78 (ONT) an 8 further accessions using the Pacific Biosciences (PacBio) platform (obtained 79 from Song et al. (2020)). The ...

show abstract

Structural variant calling: the long and the short of it

Cited by 465 publications

References 105 publications

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Copy number variants outperform SNPs to reveal genotype-temperature association in a marine species

Evolutionary genomics of structural variation in Asian rice (Oryza sativa) and its wild progenitor (O. rufipogon)

Long-read sequencing reveals widespread intragenic structural variants in a recent allopolyploid crop plant

Contact Info

Product

Resources

About