# Using CRISPR technology to study the function of paralogous genes

> **NIH NIH R24** · HARVARD MEDICAL SCHOOL · 2020 · $629,871

## Abstract

Gene annotations in model organisms such as Drosophila are important contributors to our understanding of
the functions of human genes, including human disease-associated genes. Paralogs, which share a common
ancestor, present a challenging case for identification of gene function in model organisms as in some cases,
loss of function of one paralog is masked by compensatory function of the other(s), such that only when both
are disrupted will informative phenotypes be observed. In other cases, redundancy is partial, such that
knockout of one paralog has a subset of the phenotypes observed when more than one member of the group
is disrupted simultaneously. Recent advances in CRISPR technology by our group and others makes it now
possible to systematically knockout paralog pairs in Drosophila, including in a stage- and tissue-specific
manner. We will use our existing infrastructure for bioinformatics-based identification of orthologs and
paralogs, efficient large-scale production of fly stocks, and fly stock and data sharing to develop a resource
useful for double-knockdown of paralogs. Our initial characterization of the genes with regards to signal
transduction and neurodegeneration, as well as in-depth analyses by the community, will uncover function for
paralogous genes, helping to close the ‘phenotype gap’ (lack of associated loss-of-function phenotypes) that
currently exists for nearly half of all genes in this important genetic model system. The result will be a fly stock
resource for further study by Drosophila experts, a bioinformatics pipeline and methods that can be applied to
other model systems, and a data resource that will inform annotation of fly and human genes

## Key facts

- **NIH application ID:** 9966053
- **Project number:** 5R24OD026435-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** HUGO J BELLEN
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $629,871
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966053

## Citation

> US National Institutes of Health, RePORTER application 9966053, Using CRISPR technology to study the function of paralogous genes (5R24OD026435-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9966053. Licensed CC0.

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