4.6 Article

Saturation genome editing of 11 codons and exon 13 of BRCA2 coupled with chemotherapeutic drug response accurately determines pathogenicity of variants

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Genetics & Heredity

Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup

Logan C. Walker et al.

Summary: The ACMG/AMP framework for classifying variants related to splicing potential uses six evidence categories. However, the lack of guidance on code application has led to variation in specifications developed by different panels. The ClinGen Splicing Subgroup was established to refine recommendations for applying ACMG/AMP codes. Recommendations and approaches for evaluating RNA-assay evidence aim to standardize variant classification processes based on splicing-based evidence.

AMERICAN JOURNAL OF HUMAN GENETICS (2023)

Article Biotechnology & Applied Microbiology

Saturation variant interpretation using CRISPR prime editing

Steven Erwood et al.

Summary: This study demonstrates the use of the CRISPR prime editing method for high-throughput variant classification and functional characterization. The results show that the method is efficient and accurate, and can be applied to other genes with appropriate cellular assays.

NATURE BIOTECHNOLOGY (2022)

Article Multidisciplinary Sciences

BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks

Arun Prakash Mishra et al.

Summary: The presence of homologous chromosomes in close proximity to the DNA double strand breaks compensates for the defect in the interaction between tumor suppressor BRCA2 and DSS1, allowing for normal RAD51 recruitment during meiosis.

NATURE COMMUNICATIONS (2022)

Article Genetics & Heredity

Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Leila Dorling et al.

Summary: The study found that certain rare missense variants in ATM, BRCA1, BRCA2, and CHEK2 genes may increase the risk of developing breast cancer, while missense variants in the PALB2 gene are less likely to be associated with risk.

GENOME MEDICINE (2022)

Article Genetics & Heredity

An integrative model for the comprehensive classification of BRCA1 and BRCA2 variants of uncertain clinical significance

Edwin S. Iversen et al.

Summary: Loss-of-function variants in BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer. VarCall XT, a multifactorial approach, allows for the classification of these variants using multiple forms of genetic evidence, leading to more accurate assessment of cancer risk for patients.

NPJ GENOMIC MEDICINE (2022)

Article Genetics & Heredity

Multiparametric and accurate functional analysis of genetic sequence variants using CRISPR-Select

Yiyuan Niu et al.

Summary: The study presents a flexible knock-in assay method called CRISPR-Select(TIME), CRISPR-Select(SPACE) and CRISPR-Select(STATE), which tracks the absolute frequencies of genetic variants associated with genetic diseases as a function of time, space, or measurable cell states. The method accurately determines the function of the genetic variants and can be used in research, diagnostics, and drug development for genetic disorders.

NATURE GENETICS (2022)

Review Genetics & Heredity

Scalable Functional Assays for the Interpretation of Human Genetic Variation

Daniel Tabet et al.

Summary: Scalable sequence-function studies have enabled systematic analysis of genetic variants, improving clinical interpretation and providing insights into the effects of genetic variants.

ANNUAL REVIEW OF GENETICS (2022)

Article Multidisciplinary Sciences

Multi-pathway DNA-repair reporters reveal competition between end-joining, single-strand annealing and homologous recombination at Cas9-induced DNA double-strand breaks

Bert van de Kooij et al.

Summary: DSB-repair pathways are not fully understood, but are important for genomic stability and genome editing. This study developed fluorescent Cas9-based reporters to quantify the contribution of multiple DNA repair pathways. The researchers found that inhibiting one repair pathway can increase the activity of others, and identified specific genomic regions associated with certain repair pathways.

NATURE COMMUNICATIONS (2022)

Article Genetics & Heredity

Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria

Vikas Pejaver et al.

Summary: The American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) provide recommendations for interpreting sequence variants, specifying the use of computational predictors as evidence for pathogenicity or benignity. However, the lack of quantitative support in the score intervals defined by tool developers and ACMG/AMP recommendations that require consensus of multiple predictors is addressed by a probabilistic framework proposed by the researchers. This framework is extended to computational predictors and introduces a new standard for converting tool scores to evidence strengths.

AMERICAN JOURNAL OF HUMAN GENETICS (2022)

Article Medicine, General & Internal

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women

Leila Dorling et al.

Summary: This study sequenced samples from 60,466 women with breast cancer and 53,461 controls using a panel of 34 putative susceptibility genes, identifying associations between protein-truncating variants in certain genes and breast cancer risk. The results provide important information for genetic counseling and define genes that are most clinically useful for predicting breast cancer risk.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Genetics & Heredity

Strong functional data for pathogenicity or neutrality classify BRCA2 DNA-binding-domain variants of uncertain significance

Marcy E. Richardson et al.

Summary: Assessing 252 missense VUSs from the BRCA2 gene, functional data plays a crucial role in reclassifying VUSs and improving clinical management.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

Article Biochemistry & Molecular Biology

Massively parallel assessment of human variants with base editor screens

Ruth E. Hanna et al.

Summary: Understanding the functional consequences of single-nucleotide variants is crucial for uncovering the genetic basis of diseases. Leveraging CRISPR-Cas9 cytosine base editors, this study demonstrates a scalable approach to assay variants in mammalian cells. The use of base editor screens allows for identification of mutations conferring drug sensitivity or resistance, as well as functionalization of genetic variants through sgRNA libraries.
Article Biochemistry & Molecular Biology

Functional interrogation of DNA damage response variants with base editing screens

Raquel Cuella-Martin et al.

Summary: Through CRISPR-dependent cytosine base editing screens, this study identified over 2,000 sgRNAs that induce nucleotide variants in DNA damage response (DDR) genes, altering cellular fitness upon DNA damage. The research also discovered critical mutations in DDR regulator 53BP1 and TRAIP ligase, shedding light on their roles in cellular damage response. The findings provide valuable insights into the function of DDR genes and their implications in human diseases.
Article Genetics & Heredity

CADD-Splice-improving genome-wide variant effect prediction using deep learning-derived splice scores

Philipp Rentzsch et al.

Summary: The study compared several machine learning methods that score variant effects on splicing using an experimental dataset, integrating the best methods into general variant effect prediction models and evaluating the impact on the classification of known pathogenic variants. The inclusion of splicing DNN effect scores substantially improved predictions across multiple variant categories in the new CADD-Splice model, without compromising overall performance.

GENOME MEDICINE (2021)

Review Biochemistry & Molecular Biology

Linking genome variants to disease: scalable approaches to test the functional impact of human mutations

Gregory M. Findlay

Summary: The application of genomics in medicine has enhanced our understanding of disease mutations and molecular pathways, but determining the clinical significance of rare variants remains a challenge. Recent advances in experimental techniques have allowed for faster characterization of variant effects, providing valuable data for linking human variants to disease phenotypes.

HUMAN MOLECULAR GENETICS (2021)

Article Multidisciplinary Sciences

BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination

Rania Ghouil et al.

Summary: BRCA2 and its interactor HSF2BP are essential for meiotic recombination, with a high-affinity oligomerization-inducing interaction between the two proteins, but a repeat region in BRCA2 is not essential for mouse meiosis.

NATURE COMMUNICATIONS (2021)

Article Biotechnology & Applied Microbiology

Identification of pathogenic variants in cancer genes using base editing screens with editing efficiency correction

Changcai Huang et al.

Summary: The study developed a framework that combines base editing screens with sgRNA efficiency and outcome mapping, successfully identifying 910 loss-of-function variants in BRCA1/2 genes, including noncoding region variants found in cancer patients. These results suggest the need to reassess the clinical significance of these variants, which may help in risk assessment and treatment of breast and ovarian cancer.

GENOME BIOLOGY (2021)

Article Multidisciplinary Sciences

High-throughput functional evaluation of BRCA2 variants of unknown significance

Masachika Ikegami et al.

NATURE COMMUNICATIONS (2020)

Article Genetics & Heredity

The functional impact of variants of uncertain significance in BRCA2

Romy L. S. Mesman et al.

GENETICS IN MEDICINE (2019)

Letter Biotechnology & Applied Microbiology

CRISPResso2 provides accurate and rapid genome editing sequence analysis

Kendell Clement et al.

NATURE BIOTECHNOLOGY (2019)

Article Biochemistry & Molecular Biology

Predicting Splicing from Primary Sequence with Deep Learning

Kishore Jaganathan et al.

Article Genetics & Heredity

Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches

Lucia Guidugli et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2018)

Article Genetics & Heredity

Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework

Sean V. Tavtigian et al.

GENETICS IN MEDICINE (2018)

Article Biochemistry & Molecular Biology

Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks

Eva K. Brinkman et al.

MOLECULAR CELL (2018)

Article Multidisciplinary Sciences

Accurate classification of BRCA1 variants with saturation genome editing

Gregory M. Findlay et al.

NATURE (2018)

Article Genetics & Heredity

BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2

Melissa S. Cline et al.

PLOS GENETICS (2018)

Article Medicine, General & Internal

Exome Sequencing-Based Screening for BRCA1/2 Expected Pathogenic Variants Among Adult Biobank Participants

Kandamurugu Manickam et al.

JAMA NETWORK OPEN (2018)

Article Genetics & Heredity

PERCH: A Unified Framework for Disease Gene Prioritization

Bing-Jian Feng

HUMAN MUTATION (2017)

Article Medicine, General & Internal

Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

Karoline B. Kuchenbaecker et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2017)

Article Biochemical Research Methods

sgRNA Scorer 2.0: A Species-Independent Model To Predict CRISPR/Cas9 Activity

Raj Chari et al.

ACS SYNTHETIC BIOLOGY (2017)

Article Biotechnology & Applied Microbiology

Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines

Rajarshi Ghosh et al.

GENOME BIOLOGY (2017)

Article Genetics & Heredity

Variant Interpretation: Functional Assays to the Rescue

Lea M. Starita et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2017)

Article Multidisciplinary Sciences

Landscape of somatic mutations in 560 breast cancer whole-genome sequences

Serena Nik-Zainal et al.

NATURE (2016)

Article Biochemical Research Methods

The power of multiplexed functional analysis of genetic variants

Molly Gasperini et al.

NATURE PROTOCOLS (2016)

Article Multidisciplinary Sciences

Saturation editing of genomic regions by multiplex homology-directed repair

Gregory M. Findlay et al.

NATURE (2014)

Article Biochemistry & Molecular Biology

ClinVar: public archive of relationships among sequence variation and human phenotype

Melissa J. Landrum et al.

NUCLEIC ACIDS RESEARCH (2014)

Article Biochemical Research Methods

Genome engineering using the CRISPR-Cas9 system

F. Ann Ran et al.

NATURE PROTOCOLS (2013)

Review Oncology

BRCA1 and BRCA2: different roles in a common pathway of genome protection

Rohini Roy et al.

NATURE REVIEWS CANCER (2012)

Article Biochemistry & Molecular Biology

ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data

Kai Wang et al.

NUCLEIC ACIDS RESEARCH (2010)

Article Multidisciplinary Sciences

Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing

Tom Walsh et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Article Biochemistry & Molecular Biology

Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2

Sergey G. Kuznetsov et al.

NATURE MEDICINE (2008)

Article Genetics & Heredity

Cancer risks in BRCA2 families:: estimates for sites other than breast and ovary

CJ van Asperen et al.

JOURNAL OF MEDICAL GENETICS (2005)

Article Genetics & Heredity

Integrated evaluation of DNA sequence variants of unknown clinical significance:: Application to BRCA1 and BRCA2

DE Goldgar et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2004)