scholarly journals Mimicry and mitonuclear discordance in nudibranchs: New insights from exon capture phylogenomics

2020 ◽  
Vol 10 (21) ◽  
pp. 11966-11982
Author(s):  
Kara K. S. Layton ◽  
Jose I. Carvajal ◽  
Nerida G. Wilson
Keyword(s):  
Exon Capture

scholarly journals Is Sexual Conflict a Driver of Speciation? A Case Study With a Tribe of Brush-footed Butterflies

2020 ◽  
Author(s):  
Ana Paula S Carvalho ◽  
Ryan A St Laurent ◽  
Emmanuel F A Toussaint ◽  
Caroline Storer ◽  
Kelly M Dexter ◽  
...  
Keyword(s):  
Sexual Conflict ◽  
Abiotic Factors ◽  
Evolutionary Mechanisms ◽  
Diversification Rates ◽  
Exon Capture ◽  
Key Driver ◽  
Underlying Mechanisms ◽  
Analytical Approaches ◽  
Acting In Concert

Abstract Understanding the evolutionary mechanisms governing the uneven distribution of species richness across the tree of life is a great challenge in biology. Scientists have long argued that sexual conflict is a key driver of speciation. This hypothesis, however, has been highly debated in light of empirical evidence. Recent advances in the study of macroevolution make it possible to test this hypothesis with more data and increased accuracy. In the present study, we use phylogenomics combined with four different diversification rate analytical approaches to test whether sexual conflict is a driver of speciation in brush-footed butterflies of the tribe Acraeini. The presence of a sphragis, an external mating plug found in most species among Acraeini, was used as a proxy for sexual conflict. Diversification analyses statistically rejected the hypothesis that sexual conflict is associated with shifts in diversification rates in Acraeini. This result contrasts with earlier studies and suggests that the underlying mechanisms driving diversification are more complex than previously considered. In the case of butterflies, natural history traits acting in concert with abiotic factors possibly play a stronger role in triggering speciation than does sexual conflict. [Acraeini butterflies; arms race; exon capture phylogenomics; Lepidoptera macroevolution; sexual selection; sphragis.]

scholarly journals Exon capture optimization in large-genome amphibians

2015 ◽  
Author(s):  
Evan McCartney-Melstad ◽  
Genevieve G. Mount ◽  
H. Bradley Shaffer
Keyword(s):  
Model Organisms ◽  
Tiger Salamander ◽  
Illumina Hiseq ◽  
F1 Hybrid ◽  
Large Genome ◽  
Sequence Capture ◽  
Exon Capture ◽  
Target Capture ◽  
Individual Input ◽  
Enrichment Efficiency

Background Gathering genomic-scale data efficiently is challenging for non-model species with large, complex genomes. Transcriptome sequencing is accessible for even large-genome organisms, and sequence capture probes can be designed from such mRNA sequences to enrich and sequence exonic regions. Maximizing enrichment efficiency is important to reduce sequencing costs, but, relatively little data exist for exon capture experiments in large-genome non-model organisms. Here, we conducted a replicated factorial experiment to explore the effects of several modifications to standard protocols that might increase sequence capture efficiency for large-genome amphibians. Methods We enriched 53 genomic libraries from salamanders for a custom set of 8,706 exons under differing conditions. Libraries were prepared using pools of DNA from 3 different salamanders with approximately 30 gigabase genomes: California tiger salamander (Ambystoma californiense), barred tiger salamander (Ambystoma mavortium), and an F1 hybrid between the two. We enriched libraries using different amounts of c0t-1 blocker, individual input DNA, and total reaction DNA. Enriched libraries were sequenced with 150 bp paired-end reads on an Illumina HiSeq 2500, and the efficiency of target enrichment was quantified using unique read mapping rates and average depth across targets. The different enrichment treatments were evaluated to determine if c0t-1 and input DNA significantly impact enrichment efficiency in large-genome amphibians. Results Increasing the amounts of c0t-1 and individual input DNA both reduce the rates of PCR duplication. This reduction led to an increase in the percentage of unique reads mapping to target sequences, essentially doubling overall efficiency of the target capture from 10.4% to nearly 19.9%. We also found that post-enrichment DNA concentrations and qPCR enrichment verification were useful for predicting the success of enrichment. Conclusions Increasing the amount of individual sample input DNA and the amount of c0t-1 blocker both increased the efficiency of target capture in large-genome salamanders. By reducing PCR duplication rates, the number of unique reads mapping to targets increased, making target capture experiments more efficient and affordable. Our results indicate that target capture protocols can be modified to efficiently screen large-genome vertebrate taxa including amphibians.

scholarly journals An Exon-Capture System for the Entire Class Ophiuroidea

2015 ◽  
Vol 33 (1) ◽  
pp. 281-294 ◽  
Author(s):  
Andrew F. Hugall ◽  
Timothy D. O’Hara ◽  
Sumitha Hunjan ◽  
Roger Nilsen ◽  
Adnan Moussalli
Keyword(s):  
Entire Class ◽  
Exon Capture

scholarly journals Gene markers for exon capture and phylogenomics in ray‐finned fishes

2019 ◽  
Vol 9 (7) ◽  
pp. 3973-3983 ◽  
Author(s):  
Jiamei Jiang ◽  
Hao Yuan ◽  
Xin Zheng ◽  
Qian Wang ◽  
Ting Kuang ◽  
...  
Keyword(s):  
Gene Markers ◽  
Exon Capture

Identification of Somatically Acquired Gene Mutations In the Kineome and Exome In CLL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2410-2410
Author(s):  
Xiaosong Zhang ◽  
Meng Li ◽  
Peter Ouillette ◽  
Luis Diaz ◽  
Marcelo Reis ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Conflicts Of Interest ◽  
Single Gene ◽  
Gene Mutations ◽  
P53 Mutations ◽  
Kinase Gene ◽  
Immunoglobulin Receptor ◽  
Paired Samples ◽  
Exon Capture ◽  
Exome Sequence

Abstract Abstract 2410 The pathogenesis of CLL remains incompletely understood. While acquired chromosomal aberrations have been demonstrated to influence CLL biology and clinical behavior, it remains unclear what single gene defects other than p53 or ATM mutations contribute to or cause the CLL phenotype. In particular, recurrent gene mutations that are increasingly found in other hematological malignancies have not yet been identified in CLL. Further, the discovery of stereotypical immunoglobulin receptor genes in CLL has been advanced in support of the involvement of autoantigenes in the pathogenesis of CLL and thus a pro-proliferative or anti-apoptotic gene mutation may possibly not exist in CLL. Given that kinase genes are often the targets for recurrent gene mutations and given the prospect for identification of drugable targets, we have analyzed 515 kinase genes in a discovery panel of 23 well characterized CLL samples (in DNA from CD19+ sorted cells) and tested their somatic nature in CD3+ cell-derived DNA from the same patients. A total of 8308 different exon sequences were analyzed. We identified six individual kinase gene mutations (WEE1, NEK1, BRAF, KDR, MAP4K3 and TRPM6), each occurring once in a separate CLL case as well as >1450 non-synonymous polymorphisms but no recurrent kinase gene mutations were identified. Interestingly, mutations in all these genes but NEK1 had previously been identified in cancer genome projects of cancers of the breast, colorectum, pancreas and glioblastome multiforme and WEE1, BRAF and KDR have established roles in cancer biology. Next we used solution exon capture of genomic DNA followed by Solexa-based next gen exome sequencing on 8 paired CLL derived DNA samples (FACS-sorted CD19+ versus CD3+ paired samples), including 2 samples with known p53 mutations. Using stringent criteria for mutation calling, we identified 69 mutated genes including the 2 cases of p53 mutations. None of the mutated genes were recurrent. Work is in progress to estimate the frequency of mutations in these genes in a wider panel of CLL cases. In summary, our data provide practical information about the mutations state of the CLL kineome and exome with implications for CLL biology/pathogenesis. This data should motivate additional exome sequence analyses of more CLL samples to fully capture and describe the mutation load in CLL. Disclosures: No relevant conflicts of interest to declare.

Molecular features of BRCA1/2 and PALB2 mutation associated pancreatic cancer (PAC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 206-206
Author(s):  
Maeve Aine Lowery ◽  
Kirsten Timms ◽  
Victor Abkevich ◽  
C Neff ◽  
Alexander Gutin ◽  
...  
Keyword(s):  
Parp Inhibitors ◽  
Kras Mutations ◽  
Therapeutic Implications ◽  
Molecular Features ◽  
Exon Capture ◽  
Repair Deficiency ◽  
Genome Wide ◽  
Palb2 Mutation ◽  
Increased Sensitivity ◽  
Year 2000

206 Background: Several clinical reports have indicated increased sensitivity to DNA damaging agents and PARP inhibitors in patients with PAC arising on a background of known BRCA1/2 or PALB2 germline mutation. While the mechanism of tumorigenesis in these cancer remains unclear, it appears likely that BRCA1/2germline mutations can predispose to PAC via 2 mechanisms, only one of which requires loss of the second allele. Determination as to whether biallelic inactivation of these genes is present in the tumor may have important therapeutic implications in predicting sensitivity to PARP inhibitors and other strategies targeting DNA repair. Methods: Following approval by the IRB and human bio specimen utilization committee at MSKCC, full exon sequencing of coding regions of 28 genes including BRCA1, 2 and PALB2 using exon capture by hybridization and next generation sequencing was performed on DNA extracted from 135 PAC samples. In addition, samples were analyzed for the presence of BRCA1 promotor methylation, KRAS hotspot mutations, and genome wide loss of heterozygosity (LOH) as an exploratory assessment of number and length of LOH as a marker of homologous repair deficiency / genomic instability. All patients underwent surgery for PAC at MSKCC after year 2000. Patients were selected on the basis of survival and included if they suffered a cancer-specific death within 1 year of resection or survived at least 30 months. Results: 7 tumors had mutations in BRCA2, 1 in BRCA1 and 1 in PALB2. Of 4 BRCA2 mutated samples evaluated for LOH at the BRCA2 locus, 2 demonstrated LOH while 2 did not. There was no LOH at PALB2 in the sample where a mutation was identified. Activating KRAS mutations were identified in BRCA2 mutated tumors with and without LOH. Methylation of the BRCA1promotor regions was not identified. Conclusions: The frequency of BRCA1/2 mutation carriers was as anticipated in this population. Biallelic loss of BRCA2 or PALB2 are not required for pancreatic tumorigenesis. The benefit of PARP inhibitors in BRCA1 / 2 mutated PAC may be limited to tumors with LOH of these genes. Inactivation of BRCA1 through promoter methylation is not identified in sporadic PAC.

Defining the DNA damage repair (DDR) genomic landscape of urothelial carcinoma of the bladder (UCB).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
Shawn Dason ◽  
Victor McPherson ◽  
Min Yuen Teo ◽  
Sumit Isharwal ◽  
François Audenet ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Low Grade ◽  
High Grade ◽  
Missense Mutations ◽  
Sequencing Data ◽  
Disease Spectrum ◽  
Exon Capture ◽  
Platinum Based Chemotherapy ◽  
Unknown Significance ◽  
Carcinoma Of The Bladder

502 Background: Impaired DDR is associated with response to platinum-based chemotherapy. Several genomically directed trials have been proposed using DDR alteration status for enrolment. In this study, we characterized the deleterious DDR alteration (DDRa) landscape of UCB across various clinical states. Methods: Targeted exon capture and sequencing of at least 341 cancer-associated genes was performed prospectively on 451 UCB specimens (MSK-IMPACT assay). We assessed sequencing data for deleterious alterations in 34 genes representing canonical DDR pathways. Deleterious alterations included truncating mutations, homozygous deletions, and functionally validated missense mutations. Results: Table 1. In NMIBC, deleterious DDRa were enriched in high-grade disease ([39/136, 28.7%] high grade vs. low-grade [2/28, 7.1%]; p=0.02). The frequency of deleterious DDRa in chemo-naïve MIBC was enriched relative to unmatched post-neoadjuvant chemotherapy (NAC) residual MIBC ([33/112, 29.5%] vs. [8/55, 14.5%]; p=0.01). Patients with metastatic disease had similar rates of deleterious DDRa to MIBC ([31/116, 26.7%] vs. [33/112, 29.5%]). The percentage of patients having any type of DDR alteration was similar across states. The proportion of patients with a deleterious DDRa relative to any DDRa was 41/77 (53.2%) in NMIBC, 33/65 (50.8%) in chemo-naïve MIBC, 8/27(29.6%) in post-NAC residual MIBC, and 31/68 (45.6%) in metastatic disease. Conclusions: DDRa are found across the UCB disease spectrum. ERCC2 and ATM are the most common DDRa although alterations were seen in most other DDR genes. Many alterations are of unknown significance and further characterization is needed to develop genomically directed treatment. [Table: see text]

scholarly journals Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors

2016 ◽  
Vol 34 (33) ◽  
pp. 4000-4007 ◽  
Author(s):  
Aditya Bagrodia ◽  
Byron H. Lee ◽  
William Lee ◽  
Eugene K. Cha ◽  
John P. Sfakianos ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cisplatin Resistance ◽  
Residual Disease ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Collaborative Group ◽  
Resistant Disease ◽  
Exon Capture ◽  
Whole Exome ◽  
Risk Of Cancer

Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture–based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic profiling of patients with advanced GCT could improve current risk stratification and identify novel therapeutic approaches for patients with cisplatin-resistant disease.

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