scholarly journals Whole-Exome Sequencing for Identification of Genetic Variants Involved in Vitamin D Metabolic Pathways in Families With Vitamin D Deficiency in Saudi Arabia

2021 ◽  
Vol 12 ◽  
Author(s):  
Shatha Alharazy ◽  
Muhammad Imran Naseer ◽  
Eman Alissa ◽  
Margaret Denise Robertson ◽  
Susan Lanham-New ◽  
...  
Keyword(s):  
Vitamin D ◽  
Saudi Arabia ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Nucleotide Polymorphisms ◽  
Casr Gene ◽  
Whole Exome

BackgroundNumerous research studies have found an association between vitamin D (vitD) status and single-nucleotide polymorphisms (SNPs) in genes involved in vitD metabolism. It is notable that the influence of these SNPs on 25-hydroxyvitamin D [25(OH)D] levels might vary in different populations. In this study, we aimed to explore for genetic variants in genes related to vitD metabolism in families with vitD deficiency in Saudi Arabia using whole-exome sequencing (WES).MethodsThis family-based WES study was conducted for 21 families with vitD deficiency (n = 39) in Saudi Arabia. WES was performed for DNA samples, then resulting WES data was filtered and a number of variants were prioritized and validated by Sanger DNA sequencing.ResultsSeveral missense variants in vitD-related genes were detected in families. We determined two variants in low-density lipoprotein 2 gene (LRP2) with one variant (rs2075252) observed in six individuals, while the other LRP2 variant (rs4667591) was detected in 13 subjects. Single variants in 7-dehydrocholesterol reductase (DHCR7) (rs143587828) and melanocortin-1 receptor (MC1R) (rs1805005) genes were observed in two subjects from two different families. Other variants in group-specific component (GC), cubilin (CUBN), and calcium-sensing receptor (CASR) gene were found in index cases and controls. Polymorphisms in GC (rs9016) and CASR (rs1801726) were found in the majority of family cases (94 and 88%), respectively.ConclusionIn vitD-deficient families in Saudi Arabia, we were able to detect a number of missense exonic variants including variants in GC (rs9016), CUBN (rs1801222), CASR (rs1801726), and LRP2 (rs4667591). However, the existence of these variants was not different between affected family members and non-affected controls. Additionally, we were able to find a mutation in DHCR7 (rs143587828) and a polymorphism in LRP2 (rs2075252), which may affect vitD levels and influence vitD status. Further studies are now required to confirm the association of these variants with vitD deficiency.

scholarly journals Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

2021 ◽  
Vol 2 (1) ◽  
pp. 100383
Author(s):  
Nicholas S. Diab ◽  
Spencer King ◽  
Weilai Dong ◽  
Garrett Allington ◽  
Amar Sheth ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
De Novo ◽  
Whole Exome ◽  
Analysis Workflow

scholarly journals Identification of rare genetic variants in Juvenile Idiopathic Arthritis using whole exome sequencing

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
E Sanchez ◽  
S Grandemange ◽  
F Tran Mau-Them ◽  
P Louis-Plence ◽  
A Carbasse ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Rare Genetic Variants

Whole Exome Sequencing in Patients With Ossification of the Spinal Ligaments

2021 ◽  
Author(s):  
Jiliang Zhai ◽  
Jiahao Li ◽  
Yu Zhao ◽  
Xing Wei
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Vital Role ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Clinical Presentations ◽  
Spinal Ligaments ◽  
Neurological Pathology

Abstract Background The clinical presentations of ossification of spinal ligament (OSL) are majorly myelopathy and/or radiculopathy, with serious neurological pathology resulting in paralysis of extremities and disturbances of motility (motor function) lowering the quality of life. Currently, studies find that missense single nucleotide polymorphisms (SNPs) play a vital role in the susceptibility for complex diseases. Methods In the present study, we used whole exome sequencing (WES) method to explore variants in exomes and found out novel potential responsible genes for OSL. Genomic DNA was extracted from ligamentum flavum collected from 5 OSL patients and 5 control patients. Whole-exome sequencing was then performed, while variation forecasts and conservation examination were subsequently assessed. Results 8 common SNP variants were exhibited in all 5 subjects of OSL, presented in the genes of GRHL2, CUL3, WHAMM, IL17RD, POM121L12, SLC26A8 and PTPN23. After screened with numbers of samples and additional screenings with deleterious Polyphen2_HDIV_score, Polyphen2_HVAR_score and SIFT, 4 common SNP variants were displayed in 4 subjects of OSL, presented in the genes of KRT84, KIF1B, NRAP and CETN1. 7 common SNP variants were existed in 3 subjects of OSL, presented in the genes of CCT3, ANLN, ESRRB, SRBD1, ODF3L1, BRAT1 and RBP3. Conclusion We found out novel potential variants in several genes, especially WHAMM, KIF1B and ESRRB, which represented potentially pathogenic mutations in patients with OSL.

Investigation of the role of vitamin D metabolism in South African breast cancer patients using whole exome sequencing

The Breast ◽  
2019 ◽  
Vol 44 ◽  
pp. S36
Author(s):  
A. Okunola ◽  
R. Torrorey-Sawe ◽  
K.J. Baatjes ◽  
A.E. Zemlin ◽  
R.T. Erasmus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Exome Sequencing ◽  
Cancer Patients ◽  
South African ◽  
Whole Exome Sequencing ◽  
Breast Cancer Patients ◽  
Vitamin D Metabolism ◽  
Whole Exome

scholarly journals Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Haematologica ◽  
2016 ◽  
Vol 101 (10) ◽  
pp. 1170-1179 ◽  
Author(s):  
B. Johnson ◽  
G. C. Lowe ◽  
J. Futterer ◽  
M. Lordkipanidze ◽  
D. MacDonald ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Inherited Thrombocytopenia

scholarly journals Comprehensive genetic analysis by whole exome sequencing in 352 Korean pediatric patients with unknown neurodevelopmental disorders

2018 ◽  
Author(s):  
Youngha Lee ◽  
Jin Sook Lee ◽  
Soo Yeon Kim ◽  
Jaeso Cho ◽  
Yongjin Yoo ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Neurodevelopmental Disorders ◽  
Pediatric Patients ◽  
Medical System ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Novel Variants

AbstractImportanceAccurate diagnosis of pediatric patients with complicated neurological problems demands a well-coordinated combination of robust genetic analytic capability and delicate clinical evaluation. It should be tested whether this challenge can be augmented by whole exome sequencing (WES).ObjectiveTo evaluate the utility of WES-based diagnosis and discovery of novel variants of undiagnosed patients with complex neurodevelopmental problems in a country with a centralized medical system.Design, setting, and participantsA cohort of 352 Korean patients, believed to cover a major portion of the entire country from July 2014 to April 2017, with a broad spectrum of neurodevelopmental disorders without any pathogenic variants revealed by conventional methods were evaluated by trio-based WES at Seoul National University Children’s Hospital.ExposuresWES of patients and parents and subsequent evaluation of genetic variants.Main outcomes and measuresGenetic variants from each patient were evaluated for known disease association and novel variants were assessed for possible involvement with neurodevelopment process.ResultsWe identified disease-causing variants, including newly discovered variants, in 57.4% of the probands, who had underwent a mean of 5.6 years of undiagnosed periods and visited mean of 2.3 tertiary hospitals. The cohort included 112 patients with variants that were previously reported as pathogenic (31.8%), 16 patients with copy number variants (4.5%) and 27 patients with variants that were associated with different clinical symptoms (7.7%). We also discovered potentially pathogenic variants from 47 patients that required further functional assessments (13.4%) and demonstrated potential implications in neurodevelopmental disorders. Following the genetic analysis, we provided more precise treatments to selected patients. A few clinical vignettes are presented that illuminate the potential diagnostic pitfalls that one could have encountered without this approach.Conclusions and relevanceOur results highlight the utility of WES-based diagnosis for improved patient care in a country with a centralized medical system and discovery of novel pathophysiology mechanisms.Key pointsQuestionWhat is the advantage of whole exome sequencing based diagnosis of pediatric neurology patients with unknown rare symptoms in a large tertiary clinic in a country with a centralized medical system?FindingsWhole exome sequencing of 352 Korean patients, with a mean of 5.7 years of undiagnosed period, yielded 44.0% of conservative diagnostic yield. A number of cases were directly benefitted by trio-based WES via termination of diagnostic odyssey, genetic counseling for next offspring, or suggestion of more effective and customized treatment options.MeaningWe report on the establishment of a national-level whole exome-based diagnosis system, with emphasis on deliberate integration of clinical interpretation and genetic analysis. Whole exome sequencing should be a choice of diagnostic tools for pediatric neurologic patients with ambiguous symptoms.

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