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Citation
Baradaran-Heravi, A., Cho, K.S., Tolhuis, B., Sanyal, M., Morozova, O., Morimoto, M., Elizondo, L.I., Bridgewater, D., Lubieniecka, J., Beirnes, K., Myung, C., Leung, D., Fam, H.K., Choi, K., Huang, Y., Dionis, K.Y., Zonana, J., Keller, K., Stenzel, P., Mayfield, C., Lücke, T., Bokenkamp, A., Marra, M.A., van Lohuizen, M., Lewis, D.B., Shaw, C., Boerkoel, C.F. (2012). Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression.  Hum. Mol. Genet. 21(11): 2572--2587.
FlyBase ID
FBrf0218299
Publication Type
Research paper
Abstract

Biallelic mutations of the DNA annealing helicase SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1) cause Schimke immuno-osseous dysplasia (SIOD, MIM 242900), an incompletely penetrant autosomal recessive disorder. Using human, Drosophila and mouse models, we show that the proteins encoded by SMARCAL1 orthologs localize to transcriptionally active chromatin and modulate gene expression. We also show that, as found in SIOD patients, deficiency of the SMARCAL1 orthologs alone is insufficient to cause disease in fruit flies and mice, although such deficiency causes modest diffuse alterations in gene expression. Rather, disease manifests when SMARCAL1 deficiency interacts with genetic and environmental factors that further alter gene expression. We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD.

PubMed ID
PubMed Central ID
PMC3349428 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Location data for Marcal1 deletion.
Morimoto and Boerkoel, 2014.3.07, Location data for Marcal1 deletion. [FBrf0224344]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Hum. Mol. Genet.
    Title
    Human Molecular Genetics
    Publication Year
    1992-
    ISBN/ISSN
    0964-6906
    Data From Reference