Article
Biochemistry & Molecular Biology
Yaxuan Liu, Hafdis T. Helgadottir, Pedram Kharaziha, Jungmin Choi, Francesc Lopez-Giraldez, Shrikant M. Mane, Veronica Hoiom, Carl Christofer Juhlin, Catharina Larsson, Svetlana Bajalica-Lagercrantz
Summary: This study aimed to identify new predisposing genes for hereditary breast cancer (HBC) using whole-exome sequencing, but no pathogenic variants in known hereditary cancer-related genes were found. Further analysis suggested that a combination of low- and intermediate-genetic-risk variants might contribute to breast cancer susceptibility in these families.
Article
Cell Biology
Jie Huang, Jun Liu, Ruiyi Tian, Kevin Liu, Patrick Zhuang, Hannah Tayla Sherman, Christoph Budjan, Michelle Fong, Min-Seo Jeong, Xue-Jun Kong
Summary: This study demonstrates the clinical feasibility and technical implementation of a WGS genetic report for patients with ASD. By using WGS data from six family trios and considering clinical symptoms and literature review, an evidence-based and transparent bioinformatics pipeline and report framework were provided. This method can contribute to a better understanding of ASD pathophysiology, early detection of associated comorbidities, and personalized treatment based on genetic information.
Article
Biochemical Research Methods
Andrea Binatti, Silvia Bresolin, Stefania Bortoluzzi, Alessandro Coppe
Summary: iWhale is a customizable pipeline based on Docker and SCons, which reliably detects somatic variants using three complementary callers and allows users to prioritize variants and genes according to different criteria. Its easy-to-use tool can run on multiple operating systems.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Cristina Tous, Carmen Munoz-Redondo, Nereida Bravo-Gil, Angela Gavilan, Raquel Maria Fernandez, Juan Antinolo, Elena Navarro-Gonzalez, Guillermo Antinolo, Salud Borrego
Summary: Thyroid carcinoma (TC) can be classified into medullary (MTC) and non-medullary (NMTC). This study aimed to identify susceptibility genes for familial NMTC and non-RET MTC using whole exome sequencing. Rare candidate segregating variants were found in 12 families, with enriched biological processes related to cell proliferation, differentiation, survival, and adhesion. These findings provide insights into molecular mechanisms underlying familial forms of MTC and NMTC, which may contribute to early detection, tailored therapies, and patient management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Harshit Khurana, Babylakshmi Muthusamy, Uday Yanamandra, Kishore Garapati, Harikrishnan Premdeep, Shankar Subramanian, Akhilesh Pandey
Summary: In this study, whole exome sequencing was performed on 27 patients with JAK2-negative polycythemia. Variants in genes involved in epigenetic processes and hematopoietic signaling were found in the majority of patients. This study opens a new avenue in evaluating and managing JAK2-negative polycythemia.
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
(2023)
Article
Genetics & Heredity
Huling Jiang, Luming Wang, Jianjun Zhu, Zepeng Ping
Summary: This study aimed to identify the susceptibility genes for preeclampsia (PE) by performing whole-exome sequencing on nine families with severe PE. Compound heterozygous variants in the NPFFR2 gene were found to be potentially associated with severe PE. This study provides clinicians and researchers with a better understanding of the molecular mechanisms underlying severe PE in pregnant women.
Article
Oncology
Ning-Yuan Lee, Melissa Hum, Pei-Yi Ong, Matthew Khine Myint, Enya H. W. Ong, Kar-Perng Low, Zheng Li, Boon-Cher Goh, Joshua K. Tay, Kwok-Seng Loh, Melvin L. K. Chua, Soo-Chin Lee, Chiea-Chuen Khor, Ann S. G. Lee
Summary: This study aimed to identify germline genetic variants associated with an increased risk of developing nasopharyngeal carcinoma (NPC). Through sequencing DNA samples from Singaporean NPC patients, the study found 17 pathogenic variants enriched in NPC patients as compared to unaffected controls. Five of these variants were supported by repeated testing on an independent set of Singaporean NPC patients and controls. The study also identified the association between specific genes (JAK2, PRDM16, LRP1B, NIN, and NKX2-1) and NPC risk. Pathway analysis revealed a higher frequency of germline mutations in endocytosis and immune-modulating pathways. Overall, this research provides important insights into the genetic predisposition of NPC.
Article
Endocrinology & Metabolism
Lin Zhou, Jing Chen, Qian Liu, Shuting Yang, Wanqin Xie, Ying Peng
Summary: Pseudoachondroplasia (PSACH) is a rare genetic disorder that affects bone and cartilage development, leading to short stature and joint problems. This study identified two novel mutations in the COMP gene associated with PSACH and demonstrated their potential to disrupt the protein structure. These findings contribute to a better understanding of the genetic causes of PSACH and can aid in diagnosis and genetic counseling.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Hematology
Yupei Shen, Yan Zhang, Ying Xiong, Zhiping Zhang, Baohua Zhang, Aihong Li, Zhaofeng Zhang, Jing Ding, Jing Du, Yan Che
Summary: This study investigated genetic risk factors for venous thromboembolism (VTE) in pregnant women through a large-scale prospective cohort study. The findings suggest that the presence of known pathogenic variants, damaging variants in thrombophilia genes, and rare damaging variants are associated with VTE in pregnancies. Exome-wide association analysis identified several genes related to basement membranes, sterol accumulation, atherosclerosis, lipid metabolism, and coagulation deficiency as potential mechanisms of VTE in pregnancies.
THROMBOSIS RESEARCH
(2022)
Article
Genetics & Heredity
Mohammad Salma, Elina Alaterre, Jerome Moreaux, Eric Soler
Summary: Var vertical bar Decrypt is a web-based tool designed to extract relevant functional information from whole-exome sequencing (WES) data. It offers various filtering and analysis tools for prioritizing gene variants. By using Var vertical bar Decrypt, we successfully identified known disease oncogenes and novel putative drivers in WES datasets of acute erythroid leukemia patients.
EPIGENETICS & CHROMATIN
(2023)
Article
Biochemistry & Molecular Biology
Dzamila M. Boguslawska, Michal Skulski, Beata Machnicka, Stanislaw Potoczek, Sebastian Kraszewski, Kazimierz Kuliczkowski, Aleksander F. Sikorski
Summary: Hereditary spherocytosis (HS) is the most commonly inherited hemolytic anemia in northern Europeans, with a new mutation identified through whole exome sequencing. Analysis of 71 genes associated with erythrocyte pathologies revealed only one SPTB gene variant that may be the molecular mechanism behind the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Clair Engelbrecht, Michael Urban, Mardelle Schoeman, Brandon Paarwater, Ansia van Coller, Deepthi Raju Abraham, Helena Cornelissen, Richard Glashoff, Monika Esser, Marlo Moller, Craig Kinnear, Brigitte Glanzmann
Summary: The use of next generation sequencing technologies has improved the clinical diagnosis of primary immunodeficiency disorders, leading to molecular diagnosis in 30% of patients, with significant alterations in clinical management for 67% of patients. This highlights the importance of expanded genetic testing in understanding the genetic and clinical spectrum of these disorders, particularly in populations with complex and heterogeneous genetic backgrounds like in Africa.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Yu-Xing Liu, Rong Yu, Yue Sheng, Liang-Liang Fan, Yao Deng
Summary: This study reports a Chinese family with cardiomyopathy and sudden cardiac death. Whole-exome sequencing was used to explore the genetic entity of this family, and a novel DES mutation was identified. The study expands the understanding of the relationship between DES mutations and hereditary cardiomyopathy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Pediatrics
Sonal Gupta, Praveen Mathur, Ashwani Kumar Mishra, Krishna Mohan Medicherla, Obul Reddy Bandapalli, Prashanth Suravajhala
Summary: The aim of this study was to identify de novo heterozygous missense variants associated with Congenital Pouch Colon (CPC) and discover variants of unknown significance. Whole exome sequencing (WES) was performed on individuals admitted to J.K. Lon Hospital in India between 2011 and 2017. Comparison of affected proband exomes with unaffected family members revealed rare variants associated with CPC. RNA-Seq was also performed to investigate differential gene expression. The study identified rare variants (TAF1B, MUC5B, and FRG1) that may contribute to CPC development, providing potential targets for intervention.
Article
Genetics & Heredity
Zekiye Altun, Hongling Yuan, Burcin Baran, Safiye Aktas, Esra Esmeray Sonmez, Can Kucuk, Nur Olgun
Summary: This study aimed to investigate genetic aberrations in neuroblastoma (NB) by comparing high and low-risk NB patients using whole-exome sequencing (WES) and to reveal the heterogeneity and association between somatic variants and clinical features. Seven NB patients with clinical data were included (4 in the low-risk group and 3 in the high-risk group). Somatic variants associated with NB genes were identified and analyzed using bioinformatics methods. Several gene variations were found in both groups, including oncogenes and tumor suppressor genes. Candidate gene variations were associated with chromatin remodeling complexes, the RAS pathway, cell proliferation, and DNA repair mechanism. Some variations were specific to high-risk patients or low-risk patients. Comparisons with the cBioportal cancer genomic database identified common gene variants in high-risk patients but not in low-risk patients. GO/KEGG enrichment analysis was performed to explore relevant biological processes and molecular pathways related to gene variants, which can help unravel the molecular mechanisms of NB tumorigenesis and the phenotypic differences between high-risk and low-risk patients.