Genetic anchoring of whole-genome shotgun assemblies

Mascher, Martin; Stein, Nils

doi:10.3389/fgene.2014.00208

Cited by 54 publications

(35 citation statements)

References 86 publications

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“…GArich regions, as with long repeats of other di-and trinucleotides, act as a primary algorithmic challenge in sequence assembling, as the sequence reads lack the capacity to span long repetitive elements [27,28]. Consistently, failures to assemble these structures have been attributable to the gaps in the human genome [29][30][31]. Characteristic fundus features of RP, such as peripheral intraretinal pigment migration and a hyperautofluorescent ring on the macula, and significant history such as nyctalopia, X-linked mode of inheritance, and severe disease at a relatively young age formed the basis for requesting targeted sequencing of the RPGR gene following the negative WES analysis.…”

Section: Discussionmentioning

confidence: 99%

Fundoscopy-directed genetic testing to re-evaluate negative whole exome sequencing results

Cho

Carvalho

Tanaka

et al. 2020

Orphanet J Rare Dis

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Background: Whole exome sequencing (WES) allows for an unbiased search of the genetic cause of a disease. Employing it as a first-tier genetic testing can be favored due to the associated lower incremental cost per diagnosis compared to when using it later in the diagnostic pathway. However, there are technical limitations of WES that can lead to inaccurate negative variant callings. Our study presents these limitations through a re-evaluation of negative WES results using subsequent tests primarily driven by fundoscopic findings. These tests included targeted gene testing, inherited retinal gene panels, whole genome sequencing (WGS), and array comparative genomic hybridization. Results: Subsequent genetic testing guided by fundoscopy findings identified the following variant types causing retinitis pigmentosa that were not detected by WES: frameshift deletion and nonsense variants in the RPGR gene, 353bp Alu repeat insertions in the MAK gene, and large exonic deletion variants in the EYS and PRPF31 genes. Deep intronic variants in the ABCA4 gene causing Stargardt disease and the GUCY2D gene causing Leber congenital amaurosis were also identified. Conclusions: Negative WES analyses inconsistent with the phenotype should raise clinical suspicion. Subsequent genetic testing may detect genetic variants missed by WES and can make patients eligible for gene replacement therapy and upcoming clinical trials. When phenotypic findings support a genetic etiology, negative WES results should be followed by targeted gene sequencing, array based approach or whole genome sequencing.

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Section: Discussionmentioning

confidence: 99%

Fundoscopy-directed genetic testing to re-evaluate negative whole exome sequencing results

Cho

Carvalho

Tanaka

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…homologous chromosomes) between species (Naish et al 2013; Kodama et al 2014). Furthermore, high quality, dense linkage maps are valuable for validating and orienting genomic scaffolds (Mascher & Stein 2014; Fierst 2015), especially for cases of residual polyploidy, large genome size, and high repeat content (Amores et al 2014; Ming & Man Wai 2015). Recent advances in sequencing, such as through reduced-representation library sequencing (e.g.…”

Section: Introductionmentioning

confidence: 99%

Salmonid chromosome evolution as revealed by a novel method for comparing RADseq linkage maps

et al. 2016

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Whole genome duplication (WGD) can provide material for evolutionary innovation. Family Salmonidae is ideal for studying the effects of WGD as the ancestral salmonid underwent WGD relatively recently, ∼65 Ma, then rediploidized and diversified. Extensive synteny between homologous chromosome arms occurs in extant salmonids, but each species has both conserved and unique chromosome arm fusions and fissions. Assembly of large, outbred eukaryotic genomes can be difficult, but structural rearrangements within such taxa can be investigated using linkage maps. RAD sequencing provides unprecedented ability to generate high-density linkage maps for nonmodel species, but can result in low numbers of homologous markers between species due to phylogenetic distance or differences in library preparation. Here, we generate a high-density linkage map (3,826 markers) for the Salvelinus genera (Brook Charr S. fontinalis), and then identify corresponding chromosome arms among the other available salmonid high-density linkage maps, including six species of Oncorhynchus, and one species for each of Salmo, Coregonus, and the nonduplicated sister group for the salmonids, Northern Pike Esox lucius for identifying post-duplicated homeologs. To facilitate this process, we developed MapComp to identify identical and proximate (i.e. nearby) markers between linkage maps using a reference genome of a related species as an intermediate, increasing the number of comparable markers between linkage maps by 5-fold. This enabled a characterization of the most likely history of retained chromosomal rearrangements post-WGD, and several conserved chromosomal inversions. Analyses of RADseq-based linkage maps from other taxa will also benefit from MapComp, available at: https://github.com/enormandeau/mapcomp/

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“…orthologous chromosomes) between species (Naish et al 2013;Kodama et al 2014). Furthermore, high quality, dense linkage maps are valuable for validating and orienting genomic scaffolds (Fierst 2015;Mascher & Stein 2014), especially for cases of residual polyploidy, large genome size, and high repeat content (Ming & Man Wai 2015;Amores et al 2014). Recent advances in sequencing, such as through reducedrepresentation library sequencing (e.g.…”

Section: Introductionmentioning

confidence: 99%

Salmonid chromosome evolution as revealed by a novel method for comparing RADseq linkage maps

Sutherland

Gosselin

Normandeau

et al. 2016

Preprint

101

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Whole genome duplication (WGD) can provide material for evolutionary innovation. Family Salmonidae is ideal for studying the effects of WGD as the ancestral salmonid underwent WGD relatively recently,~65 Ma, then rediploidized and diversified. Extensive synteny between homologous chromosome arms occurs in extant salmonids, but each species has both conserved and unique chromosome arm fusions and fissions. Assembly of large, outbred eukaryotic genomes can be difficult, but structural rearrangements within such taxa can be investigated using linkage maps. RAD sequencing provides unprecedented ability to generate high-density linkage maps for nonmodel species, but can result in low numbers of homologous markers between species due to phylogenetic distance or differences in library preparation. Here, we generate a high-density linkage map (3,826 markers) for the Salvelinus genera (Brook Charr S. fontinalis), and then identify corresponding chromosome arms among the other available salmonid high-density linkage maps, including six species of Oncorhynchus, and one species for each of Salmo, Coregonus, and the nonduplicated sister group for the salmonids, Northern Pike Esox lucius for identifying post-duplicated homeologs. To facilitate this process, we developed MAPCOMP to identify identical and proximate (i.e. nearby) markers between linkage maps using a reference genome of a related species as an intermediate, increasing the number of comparable markers between linkage maps by 5-fold. This enabled a characterization of the most likely history of retained chromosomal rearrangements post-WGD, and several conserved chromosomal inversions. Analyses of RADseq-based linkage maps from other taxa will also benefit from MAPCOMP, available at: https://github. com/enormandeau/mapcomp/

show abstract

Genetic anchoring of whole-genome shotgun assemblies

Cited by 54 publications

References 86 publications

Fundoscopy-directed genetic testing to re-evaluate negative whole exome sequencing results

Fundoscopy-directed genetic testing to re-evaluate negative whole exome sequencing results

Salmonid chromosome evolution as revealed by a novel method for comparing RADseq linkage maps

Salmonid chromosome evolution as revealed by a novel method for comparing RADseq linkage maps

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