scholarly journals Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Adrienne Tin ◽  
Yong Li ◽  
Jennifer A. Brody ◽  
Teresa Nutile ◽  
Audrey Y. Chu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Large Scale ◽  
Association Studies ◽  
Serum Urate ◽  
Functional Variants ◽  
Whole Exome

Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

2020 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

scholarly journals Analysis of whole exome sequencing in severe mental illness hints at selection of brain development and immune related genes

2021 ◽  
Author(s):  
Jayant Mahadevan ◽  
Ajai Kumar Pathak ◽  
Alekhya Vemula ◽  
Ravi Kumar Nadella ◽  
Biju Viswanath ◽  
...  
Keyword(s):  
Mental Illness ◽  
Severe Mental Illness ◽  
Positive Selection ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Association Studies ◽  
Psychiatric Disease ◽  
Genome Wide Association Studies ◽  
Whole Exome ◽  
Selection Of

Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants and genes under positive selection and identified 75 genes as candidates for positive selection. Of these, 20 were previously associated with Schizophrenia, Alzheimers disease and cognitive abilities in genome wide association studies. We then checked whether any of these 75 genes were involved in common biological pathways or related to specific cellular or molecular functions. We found that immune related pathways and functions related to innate immunity such as antigen binding were over-represented. We also evaluated for the presence of Neanderthal introgressed segments in these genes and found Neanderthal introgression in a single gene out of the 75 candidate genes. However, the introgression pattern indicates the region is unlikely to be the source for selection. Our findings hint at how selection pressures in individuals from families with a history of severe mental illness may diverge from the general population. Further, it also provides insights into the genetic architecture of severe mental illness, such as schizophrenia and its link to immune factors.

scholarly journals Case Report: An Infant With Kabuki Syndrome, Alobar Holoprosencephaly and Truncus Arteriosus: A Case for Whole Exome Sequencing in Neonates With Congenital Anomalies

2021 ◽  
Vol 12 ◽  
Author(s):  
Rishika P. Sakaria ◽  
Parul G. Zaveri ◽  
Shannon Holtrop ◽  
Jie Zhang ◽  
Chester W. Brown ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Congenital Anomalies ◽  
Large Scale ◽  
Heart Diseases ◽  
Truncus Arteriosus ◽  
Kabuki Syndrome ◽  
Whole Exome ◽  
Anomalous Pulmonary Venous Return ◽  
Spectrum Of Patients

Kabuki syndrome is a rare multiple anomalies syndrome associated with mutations in KMT2D or KDM6A. It is characterized by infantile hypotonia, developmental delay and/or intellectual disability, long palpebral fissures with everted lateral third of the lower eyelids and typical facial features. Intracranial anomalies occur infrequently in patients with KS and holoprosencephaly has only been recently described. Additionally, though congenital heart diseases are common in patients with KS, to our knowledge truncus arteriosus has never been reported in a patient with KS. We present an unusual case of KS in an infant with holoprosencephaly and truncus arteriosus with partial anomalous pulmonary venous return. Duo whole exome sequencing in our patient identified a pathogenic nonsense variant in exon 10 of KMT2D (c.2782C > T; p. Gln928*) establishing the diagnosis. This report further expands the phenotypic spectrum of patients with Kabuki syndrome and emphasizes the utility of performing large scale sequencing in neonates with multiple congenital anomalies.

scholarly journals A maternal GOT1 novel variant associated with early-onset severe preeclampsia identified by whole-exome sequencing

2020 ◽  
Author(s):  
Lin Zhang ◽  
Zheng Cao ◽  
Fan Feng ◽  
Ya-Nan Xu ◽  
LIN LI ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Perinatal Death ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Mutation Site ◽  
Whole Exome

Abstract Background This study wants to know the genetic cause of preeclampsia (PE) which is a leading cause of maternal and perinatal death, but the underlying molecular mechanisms that cause PE remain poorly understood. Many single nucleotide polymorphisms have been identified by genome-wide association studies and were found to be associated with PE; however, few studies have used whole-exome sequencing (WES) to identify PE mutations. Methods Five patients with severe early-onset preeclampsia (EOPE) were recruited, and WES was performed on each patient. Sanger sequencing was used to confirm the potential causative genetic mutation. Results After a stringent bioinformatics analysis, a rare mutation in the GOT1 gene, c.44C>G:p.P15R, was found in one patient. Bioinformatics analysis showed that the mutation site is highly conserved across several species and was predicted to be a pathogenic mutation according to several online mutational function prediction software packages. Further structural biology homology modeling suggested that P15R would change the electric environment of enzymatic center, and might affect the binding affinity of substrate or product. Conclusion We demonstrated for the first time that the mutation in GOT1 may be associated with EOPE, the results of this study provide researchers and clinicians with a better understanding of the molecular mechanisms that underlie maternal severe EOPE.

scholarly journals The use of PanDrugs to prioritize anticancer drug treatments in a case of T-ALL based on individual genomic data

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Pablo Fernández-Navarro ◽  
Pilar López-Nieva ◽  
Elena Piñeiro-Yañez ◽  
Gonzalo Carreño-Tarragona ◽  
Joaquín Martinez-López ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Lymphoblastic Leukaemia ◽  
Large Scale ◽  
Genomic Medicine ◽  
Fusion Transcript ◽  
Sequencing Technologies ◽  
Dna And Rna ◽  
Whole Exome ◽  
New Treatment

Abstract Background Acute T-cell lymphoblastic leukaemia (T-ALL) is an aggressive disorder derived from immature thymocytes. The variability observed in clinical responses on this type of tumours to treatments, the high toxicity of current protocols and the poor prognosis of patients with relapse or refractory make it urgent to find less toxic and more effective therapies in the context of a personalized medicine of precision. Methods Whole exome sequencing and RNAseq were performed on DNA and RNA respectively, extracted of a bone marrow sample from a patient diagnosed with tumour primary T-ALL and double negative thymocytes from thymus control samples. We used PanDrugs, a computational resource to propose pharmacological therapies based on our experimental results, including lists of variants and genes. We extend the possible therapeutic options for the patient by taking into account multiple genomic events potentially sensitive to a treatment, the context of the pathway and the pharmacological evidence already known by large-scale experiments. Results As a proof-of-principle we used next-generation-sequencing technologies (Whole Exome Sequencing and RNA-Sequencing) in a case of diagnosed Pro-T acute lymphoblastic leukaemia. We identified 689 disease-causing mutations involving 308 genes, as well as multiple fusion transcript variants, alternative splicing, and 6652 genes with at least one principal isoform significantly deregulated. Only 12 genes, with 27 pathogenic gene variants, were among the most frequently mutated ones in this type of lymphoproliferative disorder. Among them, 5 variants detected in CTCF, FBXW7, JAK1, NOTCH1 and WT1 genes have not yet been reported in T-ALL pathogenesis. Conclusions Personalized genomic medicine is a therapeutic approach involving the use of an individual’s information data to tailor drug therapy. Implementing bioinformatics platform PanDrugs enables us to propose a prioritized list of anticancer drugs as the best theoretical therapeutic candidates to treat this patient has been the goal of this article. Of note, most of the proposed drugs are not being yet considered in the clinical practice of this type of cancer opening up the approach of new treatment possibilities.

scholarly journals Development and performance of a targeted whole exome sequencing enrichment kit for the dog (Canis Familiaris Build 3.1)

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Bart J. G. Broeckx ◽  
Frank Coopman ◽  
Geert E. C. Verhoeven ◽  
Valérie Bavegems ◽  
Sarah De Keulenaer ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Reference Genome ◽  
Association Studies ◽  
Disease Association ◽  
Illumina Hiseq ◽  
Protein Coding ◽  
Whole Exome ◽  
And Performance ◽  
Average Sequencing Depth

Abstract Whole exome sequencing is a technique that aims to selectively sequence all exons of protein-coding genes. A canine whole exome sequencing enrichment kit was designed based on the latest canine reference genome (build 3.1.72). Its performance was tested by sequencing 2 exome captures, each consisting of 4 pre-capture pooled, barcoded Illumina libraries on an Illumina HiSeq 2500. At an average sequencing depth of 102x, 83 to 86% of the target regions were completely sequenced with a minimum coverage of five and 90% of the reads mapped on the target regions. Additionally, it is shown that the reproducibility within and between captures is high and that pooling four samples per capture is a valid option. Overall, we have demonstrated the strong performance of this WES enrichment kit and are confident it will be a valuable tool in future disease association studies.

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