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Complementation Tests

Complementation Tests

A complementation test is a simple cross to identify whether the two mutations are located on the same gene or different genes. It was first performed by Edward Lewis in the 1940s while working on fruit flies. He developed the test to identify the location and arrangement of different mutations on chromosomes.
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...

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Updated: May 9, 2026

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

A high-throughput functional complementation assay for classification of BRCA1 missense variants.

Peter Bouwman¹, Hanneke van der Gulden, Ingrid van der Heijden

¹1Division of Molecular Pathology and Cancer Genomics Centre and 2Department of Pathology, The Netherlands Cancer Institute Amsterdam, The Netherlands; and 3TaconicArtemis GmbH, Cologne, Germany.

Cancer Discovery

|July 23, 2013

Summary

A new high-throughput assay classifies BRCA1 variants of uncertain significance (VUS) by testing their function in mouse cells. This method aids geneticists in diagnosing hereditary breast and ovarian cancer risks more effectively.

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Last Updated: May 9, 2026

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gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair

gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair

Published on: October 6, 2014

Area of Science:

Genetics
Molecular Biology
Cancer Research

Background:

Mutations in BRCA1 and BRCA2 genes are primary causes of hereditary breast and ovarian cancers.
Sequence analysis identifies numerous BRCA1 variants of uncertain significance (VUS), complicating clinical genetic assessments.
Existing functional assays for BRCA1 VUS lack high-throughput capabilities for full-length protein analysis.

Purpose of the Study:

To develop and validate a high-throughput functional assay for classifying BRCA1 variants of uncertain significance (VUS).
To assess the functional impact of 74 unclassified BRCA1 missense mutants, particularly those in the RING and BRCT domains.

Main Methods:

A novel cDNA-based functional assay was developed.
The assay utilizes BRCA1-deficient mouse embryonic stem cells for complementation studies.
The assay measures the ability of BRCA1 VUS to functionally complement the deficient cells.

Main Results:

A fast and reliable high-throughput assay for BRCA1 VUS classification was successfully established.
The assay was validated for its ability to functionally assess BRCA1 variants.
Seventy-four unclassified BRCA1 missense mutants were analyzed using the developed assay.

Conclusions:

The developed high-throughput assay provides a reliable method for functional classification of BRCA1 VUS.
This assay addresses a critical need for clinical geneticists managing patients with hereditary breast and ovarian cancer.
The assay facilitates improved genetic risk assessment for individuals with uncertain BRCA1 variants.