Human Genetics

, Volume 137, Issue 11–12, pp 941–954 | Cite as

RNA sequencing-based transcriptomic profiles of embryonic lens development for cataract gene discovery

  • Deepti Anand
  • Atul Kakrana
  • Archana D. Siddam
  • Hongzhan Huang
  • Irfan Saadi
  • Salil A. Lachke
Original Investigation


Isolated or syndromic congenital cataracts are heterogeneous developmental defects, making the identification of the associated genes challenging. In the past, mouse lens expression microarrays have been successfully applied in bioinformatics tools (e.g., iSyTE) to facilitate human cataract-associated gene discovery. To develop a new resource for geneticists, we report high-throughput RNA sequencing (RNA-seq) profiles of mouse lens at key embryonic stages (E)10.5 (lens pit), E12.5 (primary fiber cell differentiation), E14.5 and E16.5 (secondary fiber cell differentiation). These stages capture important events as the lens develops from an invaginating placode into a transparent tissue. Previously, in silico whole-embryo body (WB)-subtraction-based “lens-enriched” expression has been effective in prioritizing cataract-linked genes. To apply an analogous approach, we generated new mouse WB RNA-seq datasets and show that in silico WB subtraction of lens RNA-seq datasets successfully identifies key genes based on lens-enriched expression. At ≥2 counts-per-million expression, ≥1.5 log2 fold-enrichment (p < 0.05) cutoff, E10.5 lens exhibits 1401 enriched genes (17% lens-expressed genes), E12.5 lens exhibits 1937 enriched genes (22% lens-expressed genes), E14.5 lens exhibits 2514 enriched genes (31% lens-expressed genes), and E16.5 lens exhibits 2745 enriched genes (34% lens-expressed genes). Biological pathway analysis identified genes associated with lens development, transcription regulation and signaling pathways, among other functional groups. Furthermore, these new RNA-seq data confirmed high expression of established cataract-linked genes and identified new potential regulators in the lens. Finally, we developed new lens stage-specific UCSC Genome Brower annotation tracks and made these publicly accessible through iSyTE ( for user-friendly visualization of lens gene expression/enrichment to prioritize genes from high-throughput data from cataract cases.



This work was supported by the National Institutes of Health awards R01EY021505 (S.L.) from National Eye Institute, and R03DE024776 (S.L., I.S.) from National Institute of Dental and Craniofacial Research. We thank the University of Kansas Medical Center Genomics Core for generating the sequence data sets. The Genomics Core is supported by the University of Kansas School of Medicine, the Kansas Intellectual and Developmental Disability Research Center (NIH U54 HD090216) and the Molecular Regulation of Cell Development and Differentiation COBRE (5P20GM104936).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biological SciencesUniversity of DelawareNewarkUSA
  2. 2.Center for Bioinformatics and Computational BiologyUniversity of DelawareNewarkUSA
  3. 3.Department of Anatomy and Cell BiologyUniversity of Kansas Medical CenterKansas CityUSA

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