Press Release issued Sep 24, 2014: Whole exome sequencing (WES) refers to a technique for sequencing the coding region of the genome (exon). Whole exome sequencing helps to detect rare variants in the exome for identifying genomic cause of various diseases such as cancer, genetic disorders, monogenic disorders and others. Whole exome sequencing is used by research centers, pharmaceutical companies, hospitals, clinics, biotechnology companies and government institutions for sequencing of genome. Some of the application areas for whole exome sequencing are drug discovery and development, agriculture, cancer, personalized medicine, monogenic disorders, diagnostics and others.
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Whole exome sequencing (WES) has recently emerged as an effective approach for identifying genetic variants underlying human diseases. However, considerable time and labour is needed for careful investigation of candidate variants. Although filtration based on population frequencies and functional prediction scores could effectively remove common and neutral variants, hundreds or even thousands of rare deleterious variants still remain. In addition, current WES platforms also provide variant information in flanking noncoding regions, such as promoters, introns and splice sites. Despite of being recognized to harbour causal variants, these regions are usually ignored by current analysis pipelines. We present a novel computational method, called Glints, to overcome the above limitations. Glints is capable of identifying disease-causing SNVs in both coding and flanking noncoding regions from exome sequencing data. The principle behind Glints is that disease-causing variants should manifest their effect at
The Alzheimers Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with
TY - JOUR. T1 - RefCNV. T2 - Identification of gene-based copy number variants using whole exome sequencing. AU - Chang, Lun Ching. AU - Das, Biswajit. AU - Lih, Chih Jian. AU - Si, Han. AU - Camalier, Corinne E.. AU - McGregor, Paul M.. AU - Polley, Eric. PY - 2016/4/27. Y1 - 2016/4/27. N2 - With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon. The construction of the reference set includes an evaluation of the sources of variability in the coverage distribution. We observed that the processing steps had an impact on the coverage distribution. For each exon, we ...
The falling cost of DNA sequencing has made the technology affordable to many research groups, enabling researchers to link genomic variants to observed phenotypes in a range of species. This review focusses on whole exome sequencing and its applications in humans and other species. The exome has traditionally been defined to consist of only the protein coding portion of the genome; a region where mutations are likely to affect protein structure and function. There are several commercial kits available for exome sequencing in a number of species and, owing to the highly conserved nature of exons, many of these can be applied to other closely related species. The data set produced from exome sequencing is many times smaller than that of whole genome sequencing, making it more easily manageable and the analysis less complex. Exome sequencing for disease gene discovery in humans is well established and has been used successfully to identify mutations that are causative of complex and rare diseases. ...
Exome Sequencing is fast, cost effective and generates a smaller sized data for quick analysis. For whole exome sequencing cost and SNP genotyping visit 1010Genome.
We developed a sequence context based model of de novo mutations to create per-gene probabilities of mutation. We noticed a high correlation (0.94) between the probability of a synonymous mutation in a gene and the number of rare synonymous variants identified in that same gene first using the NHLBI. s Exome Sequencing Project data (evs.gs.washington.edu), then with 25,000 exomes analyzed simultaneously (see abstract by MacArthur et al). We predicted the number of variants that we would expect to see in the dataset and, in order to quantify deviations, created a Z score of the chi-squared difference between observation and expectation for both synonymous and missense variation. While the distribution of these Z scores for the synonymous variants was normal, there is a marked shift in the missense distribution towards having fewer variants than predicted ...
Deafness is a highly heterogenous disorder with over 100 genes known to underlie human non-syndromic hearing impairment. However, many more remain undiscovered, particularly those involved in the most common form of deafness: adult-onset progressive hearing loss. Despite several genome-wide association studies of adult hearing status, it remains unclear whether the genetic architecture of this common sensory loss consists of multiple rare variants each with large effect size or many common susceptibility variants each with small to medium effects. As next generation sequencing is now being utilised in clinical diagnosis, our aim was to explore the viability of diagnosing the genetic cause of hearing loss using whole exome sequencing in individual subjects as in a clinical setting. We performed exome sequencing of thirty patients selected for distinct phenotypic sub-types from well-characterised cohorts of 1479 people with adult-onset hearing loss. Every individual carried predicted pathogenic variants
Deafness is a highly heterogenous disorder with over 100 genes known to underlie human non-syndromic hearing impairment. However, many more remain undiscovered, particularly those involved in the most common form of deafness: adult-onset progressive hearing loss. Despite several genome-wide association studies of adult hearing status, it remains unclear whether the genetic architecture of this common sensory loss consists of multiple rare variants each with large effect size or many common susceptibility variants each with small to medium effects. As next generation sequencing is now being utilised in clinical diagnosis, our aim was to explore the viability of diagnosing the genetic cause of hearing loss using whole exome sequencing in individual subjects as in a clinical setting. We performed exome sequencing of thirty patients selected for distinct phenotypic sub-types from well-characterised cohorts of 1479 people with adult-onset hearing loss. Every individual carried predicted pathogenic variants
We developed and optimized technical, bioinformatic and interpretive whole exome sequencing (WES) pipelines in a CAP and CLIA certified lab to identify causative mutations underlying disease phenotypes in undiagnosed patients being evaluated clinically for genetic disorders. Approximately 13 Gb of data were generated for each clinical sample and a mean coverage of 160X was achieved with ,95% of the targeted bases covered at 20X or higher. Of the 18773 genes in our exome capture 90% have ,90% of the coding regions covered by WES. Since October 2011, over 1700 WES tests have been submitted to our clinical lab on a fee-for-service basis. The majority of ordering physicians are medical geneticists and neurologists evaluating pediatric-aged patients with neurologic phenotypes who previously had a variety of genetic and other(e.g. imaging) tests without an etiologic diagnosis. To date, 1000 WES tests have been completed and results reported. We identified 367 causative mutant alleles in 265 patients, ...
PURPOSE: To identify biological processes associated with POAG and its subtypes, high-tension (HTG) and normal-tension glaucoma (NTG), by analyzing rare potentially damaging genetic variants.METHODS: A total of 122 and 65 unrelated HTG and NTG participants, respectively, with early onset advanced POAG, 103 non-glaucoma controls and 993 unscreened ethnicity-matched controls were included in this study. Study participants without myocilin disease-causing variants and non-glaucoma controls were subjected to whole exome sequencing on an Illumina HiSeq2000. Exomes of participants were sequenced on an Illumina HiSeq2000. Qualifying variants were rare in the general population (MAF RESULTS: POAG cases showed enrichment of rare variants in camera-type eye development genes (p = 1.40×10-7, corrected p = 3.28×10-4). Implicated eye development genes were related to neuronal or retinal development. HTG cases were significantly enriched for key regulators in the unfolded protein response (UPR) (p = ...
Whole exome sequencing (WES) identification of a rare, damaging, de novo germline MYH9 variant with the IDT xGen Exome Research Panel
Background and hypothesis: Familial dilated cardiomyopathy (DCM) is genetically heterogeneous and is associated with mutations in at least 30 different genes. None of these genes have an expected diagnostic yield of more than 10% complicating genetic diagnosis. Whole exome sequencing (WES) is a powerful alternative for the identification of the causal gene, however variant interpretation remains challenging. We performed WES in a large family with autosomal dominant DCM complicated by end stage heart failure and ventricular arrhythmias. The index of this family was evaluated previously by means of targeted gene panel analysis including 28 genes, but no causal mutation was found.. Methods and results: WES was applied on 2 affected cousins. First, shared heterozygous variants (single nucleotide variants, small insertions and deletions) located inside the exon or at the exon/intron boundary were selected. Synonymous variants were excluded, except if they were located at the exon/intron boundaries. ...
Background-Bicuspid aortic valve (BAV) is the most common congenital cardiovascular malformation (CVM). Although highly heritable, few causal variants have been identified. The purpose of this study was to identify genetic variants underlying BAV by whole exome sequencing (WES) a multiplex BAV kindred. Methods and Results-WES was performed on 17 individuals from a single family (BAV = 3, other CVM = 3). Post variant calling error control metrics (ECM) were established after examining the relationship between Mendelian inheritance error rate and coverage, quality score, and call rate. To determine the most effective approach to identifying susceptibility variants from among 54,674 variants passing ECM, we evaluated three variant selection strategies frequently used in WES studies plus extended family linkage. No putative rare, high impact variants were identified in all affected but no unaffected individuals. Eight high impact variants were identified by at least two of the commonly used ...
Pinpointing genes involved in non-right-handedness has the potential to clarify developmental contributions to human brain lateralization. Major-gene models have been considered for human handedness which allow for phenocopy and reduced penetrance, i.e. an imperfect correspondence between genotype and phenotype. However, a recent genome-wide association scan did not detect any common polymorphisms with substantial genetic effects. Previous linkage studies in families have also not yielded significant findings. Genetic heterogeneity and/or polygenicity are therefore indicated, but it remains possible that relatively rare, or even unique, major-genetic effects may be detectable in certain extended families with many non-right-handed members. Here we applied whole exome sequencing to 17 members from a single, large consanguineous family from Pakistan. Multipoint linkage analysis across all autosomes did not yield clear candidate genomic regions for involvement in the trait and single-point analysis ...
Nadine Norton, Duanxiang Li, Evadnie Rampersaud, Ana Morales, Eden R. Martin, Stephan Zuchner, Shengru Guo, Michael Gonzalez, Dale J. Hedges, Peggy D. Robertson, Niklas Krumm, Deborah A. Nickerson and Ray E. Hershberger on behalf of the National Heart, Lung, and Blood Institute GO Exome Sequencing Project and the Exome Sequencing Project Family Studies Project Team ...
Human의 유전체 중에서 단백질 발현과 관련된 정보를 담고 있는 Exon 전체 영역(Exome)을 capture함으로써 Exome 부분에 대한 염기서열 정보를 알 수 있습니다. SNV(Single Nucleotide Variant), InDel(Insertion/Deletion), CNV(Copy Number Variation), Rearrangement에 대한 정보를 얻을 수 있습니다 ...
The exomes of 20 individuals with sporadic ASD patients and their parents (trio-based study) were sequenced. Totally, 21 de novo mutations were identified and 11 of these mutations were altering the protein structure. The researchers suggested that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASD.52 Sanders et al.53 showed a total of 279 identified de novo coding mutations using WES of 928 individuals. Interestingly, two independent nonsense variants disrupt the same SCN2A gene. A total of 677 individual exomes from 209 families were sequenced in 2012. Moreover, 39% (49 of 126) of the most severe de novo mutations were related with a highly interconnected β-catenin/chromatin remodelling protein network as new candidate genes for autism. In probands exomes, protein-altering mutations were observed in CHD8 and NTNG1 genes.54 In another study, Neale et al.55 assessed the role of de novo mutations by sequencing the exomes of ASD cases and their parents ...
Teaching a new course (Microbial Genomics and Bioinformatics) has kept me pretty busy this quarter, so Im a bit behind on announcing lab developments. With the bulk of teaching behind me, Im now going to play a little catch-up with the next few posts.. First up, we published a paper in BMC Genomics entitled "Exome capture from saliva produces high quality genomic and metagenomic data" in collaboration with several other research groups, most notably the labs of Brenna Henn (Stony Brook) and Jeff Kidd (U Michigan).. We collected saliva samples from several Khoesan individuals, including several that live traditional hunter-gatherer lifestyles, and subjected DNA extracted from these samples to human exome capture and sequencing. This targeted sequencing approach facilitated population genetic analysis of human coding sequences. But, a fraction of the sequences didnt show any discernible similarity to the human genome. We compared this fraction of sequences to genomes of known oral microbiota ...
Whole exome sequencing has become a pivotal methodology for rapid and cost-effective detection of pathogenic variations in Mendelian disorders. A major challenge of this approach is determining the causative mutation from a substantial number of bystander variations that do not play any role in the disease etiology. Current strategies to analyze variations have mainly relied on genetic and functional arguments such as mode of inheritance, conservation, and loss of function prediction. Here, we demonstrate that disease-network analysis provides an additional layer of information to stratify variations even in the presence of incomplete sequencing coverage, a known limitation of exome sequencing. We studied a case of Hereditary Spastic Paraparesis (HSP) in a single inbred Palestinian family. HSP is a group of neuropathological disorders that are characterized by abnormal gait and spasticity of the lower limbs. Forty-five loci have been associated with HSP and lesions in 20 genes have been ...
Paper accepted: Whole exome sequence analysis reveals a homozygous mutation in PNPLA2 as the cause of severe dilated cardiomyopathy secondary to neutral lipid storage disease in the International Journal of Cardiology
In Islas previous genetic testing she had done it had showed the variant in one copy of the CRB1 gene. In cases of LCA caused by the CRB1 gene, you would usually find change in both copies of the gene. So before they get Isla started on the Whole Exome Sequencing study, the study team wants to look at the CRB1 gene again, in a different way to be sure they are not missing a change in the second copy of the gene. This additional way of looking at the gene is called "Deletion/Duplication" Testing. Which means they will take Islas blood thats stored from the initial draw and use it to look at that particular gene again. Once this testing starts, it will be about a month before we know any answers and move forward with the Whole Exome Sequencing study. I will keep you posted as we know more ...
The haploid human genome is composed of three billion base pairs, about one percent of which consists of exonic regions, the coding sequence for functional proteins, also now known as the "exome". The development of next-generation sequencing makes it possible from a technical and economic standpoint to sequence an individuals exome but at the cost of generating long lists of gene variants that are not straightforward to interpret. Various public consortiums such as the 1000 Genomes Project and the NHLBI Exome Sequencing Project have sequenced the exomes and a subset of entire genomes of over 2500 control individuals with ongoing efforts to further catalogue genetic variation in humans.1 The use of these public databases facilitates the interpretation of these variant lists produced by exome sequencing and, as a result, novel genetic variants linked to disease are being discovered and reported at a record rate. However, the interpretation of these results and their bearing on diagnosis, ...
Continuous advancement in sequencing technologies increases the throughput of DNA sequencing, while at the same time contributes sharply to decreasing its cost. Although sequencing costs have fallen, whole genome sequencing is still quite expensive, and data interpretation remains challenging. Therefore, whole genome sequencing is not the most appropriate choice for all investigations. The ability to target certain regions of the genome, such as protein and or RNA-coding exons, is an attractive alternative for many experiments. In recent times, target enrichment by hybridization technologies has demonstrated rapid progress in development and usage by the research and diagnostic community.. We present a comparative study of four whole exome capture technologies from three manufacturers, designed to reveal important performance aspects of the technologies. To address this, we studied six parameters for each technology: the portion of target bases representing different exome databases, target ...
Adult body height is a quantitative trait for which genome-wide association studies (GWAS) have identified numerous loci, primarily in European populations. These loci, comprising common variants, explain |10% of the phenotypic variance in height. We searched for novel associations between height and common (minor allele frequency, MAF ≥5%) or infrequent (0.5% | MAF | 5%) variants across the exome in African Americans. Using a reference panel of 1692 African Americans and 471 Europeans from the National Heart, Lung, and Blood Institutes (NHLBI) Exome Sequencing Project (ESP), we imputed whole-exome sequence data into 13 719 African Americans with existing array-based GWAS data (discovery). Variants achieving a height-association threshold of P | 5E-06 in the imputed dataset were followed up in an independent sample of 1989 African Americans with whole-exome sequence data (replication). We used P | 2.5E-07 (=0.05/196 779 variants) to define statistically significant associations in meta-analyses
Shi, Fan, Tibbits, Josquin, Pasam, Raj K., Kay, Pippa, Wong, Debbie, Petkowski, Joanna, Forrest, Kerrie L., Hayes, Ben J., Akhunova, Alina, Davies, John, Webb, Steven, Spangenberg, German C., Akhunov, Eduard, Hayden, Matthew J. and Daetwyler, Hans D. (2017) Exome sequence genotype imputation in globally diverse hexaploid wheat accessions. Theoretical and Applied Genetics, 130 7: 1393-1404. doi:10.1007/s00122-017-2895-3 ...
http://ift.tt/2tsxIoU This Genetics in Medicine podcast discusses the following article: Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development http://ift.tt/2u1I8ZR via IFTTT
Congenital hyperinsulinism of infancy (CHI) is a rare disorder characterized by severe hypoglycemia due to inappropriate insulin secretion. The genetic causes of CHI have been found in genes regulating insulin secretion from pancreatic β-cells; recessive inactivating mutations in the ABCC8 and KCNJ11 genes represent the most common events. Despite the advances in understanding the molecular pathogenesis of CHI, specific genetic determinants in about 50 % of the CHI patients remain unknown, suggesting additional locus heterogeneity. In order to search for novel loci contributing to the pathogenesis of CHI, we combined a family-based association study, using the transmission disequilibrium test on 17 CHI patients lacking mutations in ABCC8/KCNJ11, with a whole-exome sequencing analysis performed on 10 probands. This strategy allowed the identification of the potential causative mutations in genes implicated in the regulation of insulin secretion such as transmembrane proteins (CACNA1A, KCNH6, ...
We used whole-exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in-silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole-brain analysis and meta-analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimers disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next-generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets.
In the current study, we found 7 variants that could affect protein function through exome sequencing followed by subsequent filtering and selection by SIFT, Polyphen-2, and MutationTaster. We searched literatures regarding potential relationship between the variants and breast cancer. Among the 7 variants, 3 variants were related to breast cancer. The XCR1, a chemokine receptor belonging to the G protein-coupled receptor superfamily, has been known to be involved in cytotoxic immune response [1718]. With regard to breast cancer, Gantsev et al. [19] demonstrated the increase in expression of the genes CCL16, XCR1, CYFIP2, and TNFSF14 in newly formed lymph nodes in breast cancer. The DLL1 gene encodes for delta-like protein 1, which acts as a ligand for Notch receptors that engage in oncogenic conversion of human breast epithelial cells [20]. Furthermore, inhibition of Notch signaling is suggested to be beneficial for breast cancer [21]. The CCNF, a member of the cyclin family, is known to be ...
Genome-wide association studies (GWAS) are widely used to identify loci associated with phenotypic traits in the domestic dog that has emerged as a model for Mendelian and complex traits. However, a disadvantage of GWAS is that it always requires subsequent fine-mapping or sequencing to pinpoint causal mutations. Here, we performed whole exome sequencing (WES) and canine high-density (cHD) SNP genotyping of 28 dogs from 3 breeds to compare the SNP and linkage disequilibrium characteristics together with the power and mapping precision of exome-guided GWAS (EG-GWAS) versus cHD-based GWAS. Using simulated phenotypes, we showed that EG-GWAS has a higher power than cHD to detect associations within target regions and less power outside target regions, with power being influenced further by sample size and SNP density. We analyzed two real phenotypes (hair length and furnishing), that are fixed in certain breeds to characterize mapping precision of the known causal mutations. EG-GWAS identified the ...
The identification of recurrent driver mutations by whole-exome sequencing (WES) of fresh-frozen human cancers and the subsequent development of novel targeted therapies have recently transformed the treatment of many cancers including melanoma. In routine clinical practice, fresh-frozen tissue is rarely available and mutation testing usually needs to be carried out on archival formalin fixed, paraffin embedded (FFPE) tissue, from which DNA is typically fragmented, cross-linked and of lower quality. In this study we aimed to determine whether WES data generated from genomic DNA (gDNA) extracted from FFPE tissues can be produced reliably and of clinically-actionable standard. In this study of ten melanoma patients, we compared WES data produced from analysis of gDNA isolated from FFPE tumour tissue with that isolated from fresh-frozen tumour tissue from the same specimen. FFPE samples were sequenced using both Illuminas Nextera and NimbleGen SeqCap exome capture kits. To examine mutations between the
Diagnostic impact and cost-effectiveness of whole-exome sequencing for ambulant children with suspected monogenic conditions", Tan, T.Y., Dillon, O.J., Stark, Z., Schofield, D., Alam, K., Shrestha, R., Chong, B., Phelan, D., Brett, G.R., Creed, E., Jarmolowicz, A., Yap, P., Walsh, M., Downie, L., Amor, D.A., Savarirayan, R., McGillivray, G., Yeung, A., Peters, H., Robertson, S.J., Robinson, A.J., Macciocca, I., Sadedin, S., Bell, K., Oshlack, A., Georgeson, P., Thorne, N., Gaff, C., White, S.M, JAMA Pediatrics. "Prospective comparison of the cost-effectiveness of the clinical whole exome sequencing to usual care overwhelmingly supports early use and reimbursement", Stark, Z., Schofield, D., Alam, K., Wilson, W., Mupfeki, N., Macciocca, I., Shrestha, R., White, S.M., Gaff, C., Genetics in Medicine. "Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy", Walsh, M., Bell, K.M., Chong, B., Creed, E., Brett, G.R., Pope, K., Thorne, N.P., Sadedin, S., Georgeson, P., Phelan, ...
Case Study: Kabuki Syndrome. As a demonstration of DNASTARs pipeline, a rare Mendelian disorder known as Kabuki syndrome was used. Exome data sets were obtained through dbGaP. These data sets were from the published Kabuki syndrome study (Ng et. al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat. Genet. 42, 30-35 (2010)). The syndrome, which is caused by autosomal dominant mutations, is rare with approximately 400 cases reported worldwide.. Ten case and eight control exome data sets were independently aligned to the human genome reference sequence using SeqMan NGen which also identified and annotated variants. Variants from each assembly were then loaded together into ArrayStar resulting in over 5.7 million independent positions located in about 32,000 genes across all samples after coalescing. The samples were then organized into two groups, Kabuki and Control, to facilitate subsequent filtering.. We first filtered at the variant level making three assumptions ...
Ns done by the Polyphen-2 software used by the Exome Variant Server (EVS) database to predict the effect of amino acid substitution on 115103-85-0 manufacturer
Analysis of mutation data.(A) Clustering of whole exome sequencing mutation data based on the mutation status of the genes in P0 and P1 samples of four models.
PreventionGenetics is pleased to offer a full menu of prenatal genetic tests, including whole exome sequencing - Prenatal PGxome®. Because of the urgent nature of prenatal testing, we have expedited turnaround times, Prenatal PGxome results are reported within 14 days.
If you havent been following along with Emmes story this post is an update to The Land Of 10,000 Lakes and Even More Questions. If you arent aware of the reasons behind our trip to Minneapolis or what the results were Id suggest reading that first. Now on to the good news….. _____________________________________________________________________________________________________________________________________. In the end all it took was a couple of phone calls. After trying numerous times to have whole exome sequencing (WES) done on Emily we finally got a yes.. Liz called our metabolic team at Riley Hospital as soon as we got back on Monday. After giving them the information from Minneapolis on the urgent need to push for whole exome sequencing they told us they would be in touch by Thursday. They mentioned the possibility that insurance would say yes, but we would still have to pay a portion. So when Liz got a call Tuesday she was surprised. Surprise turned to excitement when they said not ...
Rauch, Anita; Wieczorek, Dagmar; Graf, Elisabeth; Wieland, Thomas; Endele, Sabine; Schwarzmayr, Thomas; Albrecht, Beate; Bartholdi, Deborah; Beygo, Jasmin; Di Donato, Nataliya; Dufke, Andreas; Cremer, Kirsten; Hempel, Maja; Horn, Denise; Hoyer, Juliane; Joset, Pascal; Ropke, Albrecht; Moog, Ute; Riess, Angelika; Thiel, Christian T.; Tzschach, Andreas; Wiesener, Antje; Wohlleber, Eva; Zweier, Christiane; Ekici, Arif B.; Zink, Alexander M.; Rump, Andreas; Meisinger, Christa; Grallert, Harald; Sticht, Heinrich; Schenck, Annette; Engels, Hartmut; Rappold, Gudrun; Schrock, Evelin; Wieacker, Peter; Riess, Olaf; Meitinger, Thomas; Reis, Andre; Strom, Tim M. ...
A study presented at ASHG Tuesday showed that newly identified schizophrenia risk genes appear to have some overlap with genes involved in autism spectrum disorder.
Whole exome sequencing continues to end the diagnostic odyssey for a number of patients and expands our knowledge of phenotypes associated with gene mutations. We describe an 11-year-old female patient with a constellation of symptoms including congenital cataracts, gut dysmotility, sensory neuropathy, and bifrontal polymicrogyria. Whole exome sequencing was performed and identified a de novo heterozygous missense mutation in the ATPase motor domain of cytoplasmic dynein heavy chain 1 (DYNC1H1), which is known to be involved in neuronal migration and retrograde axonal transport. The mutation was found to be highly damaging by multiple prediction programs. The residue is highly conserved, and reported mutations in this gene result in a variety of phenotypes similar to that of our patient. We report only the second case of congenital cataracts and the first of gut dysmotility in a patient with DYNC1H1, thus expanding the spectrum of disease seen in DYNC1H1 dyneinopathies.
Cleary, S. P., Jeck, W. R., Zhao, X., Chen, K., Selitsky, S. R., Savich, G. L., Tan, T.-X., Wu, M. C., Getz, G., Lawrence, M. S., Parker, J. S., Li, J., Powers, S., Kim, H., Fischer, S., Guindi, M., Ghanekar, A. and Chiang, D. Y. (2013), Identification of driver genes in hepatocellular carcinoma by exome sequencing. Hepatology, 58: 1693-1702. doi: 10.1002/hep.26540 ...
The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions-deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions-deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed ...
Background Rapid advances in high throughput genomic technologies and next generation sequencing are making medical genomic research more readily accessible and affordable, including the sequencing of...
TY - JOUR. T1 - Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability. AU - Riazuddin, S.. AU - Hussain, M.. AU - Razzaq, A.. AU - Iqbal, Z.. AU - Shahzad, M.. AU - Polla, D. L.. AU - Song, Y.. AU - van Beusekom, E.. AU - Khan, A. A.. AU - Tomas-Roca, L.. AU - Rashid, M.. AU - Zahoor, M. Y.. AU - Wissink-Lindhout, W. M.. AU - Basra, M. A. R.. AU - Ansar, M.. AU - Agha, Z.. AU - van Heeswijk, K.. AU - Rasheed, F.. AU - Van de Vorst, M.. AU - Veltman, J. A.. AU - Gilissen, C.. AU - Akram, J.. AU - Kleefstra, T.. AU - Assir, M. Z.. AU - Grozeva, D.. AU - Carss, K.. AU - Raymond, F. L.. AU - OConnor, T. D.. AU - Riazuddin, S. A.. AU - Khan, S. N.. AU - Ahmed, Z. M.. AU - de Brouwer, A. P. M.. AU - van Bokhoven, H.. AU - Riazuddin, S.. AU - UK10K. PY - 2017/11. Y1 - 2017/11. KW - NONSYNDROMIC MENTAL-RETARDATION. KW - DE-NOVO MUTATIONS. KW - COGNITIVE DISORDERS. KW - METABOLIC CRISES. KW - NETWORKS. KW - DEAFNESS. KW - ...
Despite the many common genetic risk variants for CAD, they only account for a small percentage of the expected heritability (45). It is estimated that about 50% of predisposition for CAD is genetic (31), yet, the 36 risk variants only account for about 10% of the expected heritability. There are several possibilities to account for this discrepancy: rare risk variants (mean allele frequency ≤5%), undiscovered common variants, epistasis (gene-gene interactions), or miscalculations. GWAS has the resolution to detect common SNPs, but not rare SNPs, so they can only be detected by direct DNA sequencing. An ongoing approach instead of WGS is WES. This is a National Institutes of Health Heart, Lung, and Blood Institute-sponsored project "Exome Sequencing Project" for rare variants that involves sequencing about 30 million bases encompassing all 180,000 exons in the 23,000 genes in the genome (30). The initial results confirm the expectation that there are many more rare variants (46) than common ...
Joseph Broderick, MD, Albert Barnes Voorheis Chair of Neurology at the UC College of Medicine and research director of the UC Neuroscience Institute, is presenting the research Friday, Feb. 3, at the American Stroke Associations International Stroke Conference 2012 in New Orleans.. For the first time, scientists applied a process called whole exome sequencing to seek gene mutations in families in which multiple relatives have intracranial aneurysms-weakened, ballooned-out areas in arteries of the brain that can rupture and cause a stroke, resulting in bleeding within the brain.. Instead of sequencing the entire genome, whole exome sequencing focuses on the small portion of the genetic blueprint that provides instructions for making proteins. This approach-less costly and more efficient than whole genome sequencing-allows researchers to look for rare variations in the genetic code, Broderick said.. "For families with many people affected, it may be likely that a rare mutation leads to a problem ...
Whole exome sequencing (WES) has been extensively used for variant calling of protein-coding regions. Besides medical diagnostics for inherited diseases, WES can help address a broad spectrum of applications.
Single-cell genome sequencing methods are challenged by poor physical coverage and high error rates, making it difficult to distinguish real biological variants from technical artifacts. To address this problem, we developed a method called SNES that combines flow-sorting of single G1/0 or G2/M nuclei, time-limited multiple-displacement-amplification, exome capture, and next-generation sequencing to generate high coverage (96%) data from single human cells. We validated our method in a fibroblast cell line, and show low allelic dropout and false-positive error rates, resulting in high detection efficiencies for single nucleotide variants (92%) and indels (85%) in single cells.