A novel mutation combining with rs66612022 in a Chinese pedigree suggests a new pathogenesis to osteogenesis imperfecta via whole genome sequencing

2019 ◽  
Vol 84 (4) ◽  
pp. 339-344
Author(s):  
Yanjiao Li ◽  
Hongsuo Liang ◽  
Dekai Yuan ◽  
Baoling Liu ◽  
Ling Liu ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Novel Mutation ◽  
Whole Genome

M86 NOVEL MUTATION IN PPEF2 REPORTED IN A FAMILY AFFECTED WITH SCHIZOPHRENIA: WHOLE GENOME SEQUENCING STUDY

2019 ◽  
Vol 29 ◽  
pp. S212-S213
Author(s):  
Sandra Smieszek ◽  
Rosa Torres ◽  
Derek Xiao ◽  
Christos Polymeropoulos ◽  
Gunther Birznieks ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Novel Mutation ◽  
Whole Genome

scholarly journals Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss

2021 ◽  
Vol 8 ◽  
Author(s):  
Nourah H. Al Qahtani ◽  
Sayed AbdulAzeez ◽  
Noor B. Almandil ◽  
Norah Fahad Alhur ◽  
Hind Saleh Alsuwat ◽  
...  
Keyword(s):  
Ion Channel ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Interaction Analysis ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Recessive Mutation ◽  
Whole Genome

Family trio next-generation sequencing-based variant analysis was done to identify the genomic reason on unexplained recurrent pregnancy loss (RPL). A family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at the ninth week of pregnancy was included in the study. Whole-genome sequencing (WGS) of a dead fetus and the parents was done to identify the pathogenic variation and confirmed through Sanger sequencing. WGS of dead fetus identifies a novel homozygous exonic variation (NM_017419.3:c.680G>T) in ASIC5 (acid-sensing ion channel subunit family member 5) gene; the parents are heterozygous. Newly designed ARMS PCR followed by direct sequencing confirms the presence of heterozygous in one subject and absence of homozygous novel mutation among randomly selected healthy Saudis. The second family with heterozygous was confirmed with three unexplained RPLs. Pathogenicity analysis of R227I amino acid substitution in ASIC5 protein through molecular docking and interaction analysis revealed that the mutations are highly pathogenic, decrease the stability of the protein, and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5. The identified rare and novel autosomal recessive mutation, c.680G>T:p.R227I (ASIC5Saudi), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus.

scholarly journals Mitochondrial PITRM1 peptidase loss-of-function in childhood cerebellar atrophy

2018 ◽  
Vol 55 (9) ◽  
pp. 599-606 ◽  
Author(s):  
Yeshaya Langer ◽  
Adi Aran ◽  
Suleyman Gulsuner ◽  
Bassam Abu Libdeh ◽  
Paul Renbaum ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Whole Genome Sequencing ◽  
Spinocerebellar Ataxia ◽  
Genome Sequencing ◽  
Novel Mutation ◽  
Cerebellar Atrophy ◽  
Whole Genome ◽  
Loss Of Function ◽  
Childhood Onset ◽  
Whole Exome

ObjectiveTo identify the genetic basis of a childhood-onset syndrome of variable severity characterised by progressive spinocerebellar ataxia, mental retardation, psychotic episodes and cerebellar atrophy.MethodsIdentification of the underlying mutations by whole exome and whole genome sequencing. Consequences were examined in patients’ cells and in yeast.ResultsTwo brothers from a consanguineous Palestinian family presented with progressive spinocerebellar ataxia, mental retardation and psychotic episodes. Serial brain imaging showed severe progressive cerebellar atrophy. Whole exome sequencing revealed a novel mutation: pitrilysin metallopeptidase 1 (PITRM1) c.2795C>T, p.T931M, homozygous in the affected children and resulting in 95% reduction in PITRM1 protein. Whole genome sequencing revealed a chromosome X structural rearrangement that also segregated with the disease. Independently, two siblings from a second Palestinian family presented with similar, somewhat milder symptoms and the same PITRM1 mutation on a shared haplotype. PITRM1T931M carrier frequency was 0.027 (3/110) in the village of the first family evaluated, and 0/300 among Palestinians from other locales. PITRM1 is a mitochondrial matrix enzyme that degrades 10–65 amino acid oligopeptides, including the mitochondrial fraction of amyloid-beta peptide. Analysis of peptide cleavage activity by the PITRM1T931M protein revealed a significant decrease in the degradation capacity specifically of peptides ≥40 amino acids.ConclusionPITRM1T931M results in childhood-onset recessive cerebellar pathology. Severity of PITRM1-related disease may be affected by the degree of impairment in cleavage of mitochondrial long peptides. Disruption and deletion of X linked regulatory segments may also contribute to severity.

scholarly journals Novel mutations identified from whole-genome sequencing of SARS-CoV-2 isolated from Noakhali, Bangladesh

2021 ◽  
Author(s):  
Maqsud Hossain ◽  
Tahrima Saiha Huq ◽  
Aura Rahman ◽  
Md. Aminul Islam ◽  
Syeda Naushin Tabassum ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Novel Mutation ◽  
Temporal Distribution ◽  
Eastern Region ◽  
Whole Genome ◽  
Viral Pathogens ◽  
South Eastern ◽  
Study Results ◽  
Variant Analysis

Abstract Whole-genome sequencing is increasingly being used to investigate the spatial and temporal distribution of viral pathogens including the Severe Acute Respiratory Syndrome Coronavirus Variant 2 (SARS-CoV-2) which is responsible for the ongoing COVID-19 pandemic. In this study, we determined 55 complete genome sequences of SARS-CoV-2 strains isolated from patients from Noakhali, a South-Eastern district in Bangladesh. Variant analysis of our sequenced genomes identified sixteen rare variations in S, six in N, two in M, one in E protein and the S protein variation, Y204F, identified in two of our sequenced strains, has not been reported from any other countries in the GISAID database. Comparison of the prevalence pattern across the country showed GH clade lineages B.1.36 and B.1.36.16 to be abundant in Noakhali and the South-Eastern region of Chittagong when compared to the rest of the country. Phylodynamic analysis of our sequenced genomes revealed that the virus was estimated to be evolving at the rate of 1.065 X 10− 4 subs/site/year. The study results demonstrated the necessity of initiating a concerted, country-wide genomics surveillance effort to determine any novel mutation of functional significance, understanding virus evolution, transmission, and spread in Bangladesh. Short running title: Genome sequencing of Noakhali isolates SARS-Cov-2 in Bangladesh

Whole-genome sequencing of prostate cancer reveals novel mutation-driven processes and molecular subgroups

Life Sciences ◽  
2020 ◽  
Vol 254 ◽  
pp. 117218 ◽  
Author(s):  
Caixia Liang ◽  
Lijuan Niu ◽  
Zejun Xiao ◽  
Cuiling Zheng ◽  
Yinchen Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Novel Mutation ◽  
Whole Genome ◽  
Molecular Subgroups

scholarly journals Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Juan He ◽  
Zhen Zeng ◽  
Yuelong Wang ◽  
Jiaojiao Deng ◽  
Xin Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Whole Genome Sequencing ◽  
Signaling Pathway ◽  
Genome Sequencing ◽  
Novel Mutation ◽  
Wnt Signaling Pathway ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Whole Genome

Abstract Background Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown. Methods In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays. Results We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer β-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation. Conclusions Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of β-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.

Utility of Whole Genome Sequencing in diagnosing complex disorders: lesson from renal tubular disorders

2018 ◽  
Author(s):  
Mark Stevenson ◽  
Alistair T Pagnamenta ◽  
Heather G Mack ◽  
Judith A Savige ◽  
Kate E Lines ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Complex Disorders ◽  
Tubular Disorders ◽  
Renal Tubular Disorders ◽  
Renal Tubular

0306 Exploring the feasibility of using copy number variants as genetic markers through large-scale whole genome sequencing experiments

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 146-146
Author(s):  
D. M. Bickhart ◽  
L. Xu ◽  
J. L. Hutchison ◽  
J. B. Cole ◽  
D. J. Null ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genetic Markers ◽  
Genome Sequencing ◽  
Copy Number ◽  
Large Scale ◽  
Copy Number Variants ◽  
Whole Genome
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