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  Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster

Iyer, J., Wang, Q., Le, T., Pizzo, L., Gronke, S., Ambegaokar, S. S., et al. (2016). Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster. G3 (Bethesda), 6(5), 1427-37. doi:10.1534/g3.116.027060.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-2770-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-2771-2
Genre: Journal Article

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http://www.ncbi.nlm.nih.gov/pubmed/26994292 (Any fulltext)
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 Creators:
Iyer, J.1, Author
Wang, Q.1, Author
Le, T.1, Author
Pizzo, L.1, Author
Gronke, S.1, Author
Ambegaokar, S. S.1, Author
Imai, Y.1, Author
Srivastava, A.1, Author
Troisi, B. L.1, Author
Mardon, G.1, Author
Artero, R.1, Author
Jackson, G. R.1, Author
Isaacs, A. M.1, Author
Partridge, L.1, Author
Lu, B.1, Author
Kumar, J. P.1, Author
Girirajan, S.1, Author
Affiliations:
1Max Planck Institute for Biology of Ageing, Max Planck Society, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, DE, ou_1942284              

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Free keywords: Drosophila melanogaster human disease models modifier screens neurodevelopmental disorders ommatidia rough eye
 Abstract: About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions.

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 Dates: 2016
 Publication Status: Published in print
 Pages: -
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 Rev. Type: -
 Identifiers: Other: 26994292
DOI: 10.1534/g3.116.027060
ISSN: 2160-1836 (Electronic)2160-1836 (Linking)
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Title: G3 (Bethesda)
Source Genre: Journal
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Pages: - Volume / Issue: 6 (5) Sequence Number: - Start / End Page: 1427 - 37 Identifier: -