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Megabase deletions of gene deserts result in viable mice

Author

Listed:
  • Marcelo A. Nóbrega

    (DOE Joint Genome Institute Walnut Creek
    Genomics Division Lawrence Berkeley National Laboratory Berkeley)

  • Yiwen Zhu

    (DOE Joint Genome Institute Walnut Creek
    Genomics Division Lawrence Berkeley National Laboratory Berkeley)

  • Ingrid Plajzer-Frick

    (DOE Joint Genome Institute Walnut Creek
    Genomics Division Lawrence Berkeley National Laboratory Berkeley)

  • Veena Afzal

    (DOE Joint Genome Institute Walnut Creek
    Genomics Division Lawrence Berkeley National Laboratory Berkeley)

  • Edward M. Rubin

    (DOE Joint Genome Institute Walnut Creek
    Genomics Division Lawrence Berkeley National Laboratory Berkeley)

Abstract

The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined1. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts2,3,4 can be well tolerated by an organism. We deleted two large non-coding intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regard to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further detailed analysis of the expression of multiple genes bracketing the deletions revealed only minor expression differences in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (more than 100 base pairs, 70% identity). Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially ‘disposable DNA’ in the genomes of mammals.

Suggested Citation

  • Marcelo A. Nóbrega & Yiwen Zhu & Ingrid Plajzer-Frick & Veena Afzal & Edward M. Rubin, 2004. "Megabase deletions of gene deserts result in viable mice," Nature, Nature, vol. 431(7011), pages 988-993, October.
  • Handle: RePEc:nat:nature:v:431:y:2004:i:7011:d:10.1038_nature03022
    DOI: 10.1038/nature03022
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    Cited by:

    1. Noah Dukler & Mehreen R. Mughal & Ritika Ramani & Yi-Fei Huang & Adam Siepel, 2022. "Extreme purifying selection against point mutations in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Samuel Abassah-Oppong & Matteo Zoia & Brandon J. Mannion & Raquel Rouco & Virginie Tissières & Cailyn H. Spurrell & Virginia Roland & Fabrice Darbellay & Anja Itum & Julie Gamart & Tabitha A. Festa-Da, 2024. "A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    3. Andrea Wilderman & Eva D’haene & Machteld Baetens & Tara N. Yankee & Emma Wentworth Winchester & Nicole Glidden & Ellen Roets & Jo Dorpe & Sandra Janssens & Danny E. Miller & Miranda Galey & Kari M. B, 2024. "A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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