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No Evidence for Mutations that Deregulate GARS–AIRS–GART Protein Levels in Children with Down Syndrome

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Abstract

GARS–AIRS–GART is crucial in studies of Down syndrome (DS)-related mental retardation due to its chromosomal location (21q22.1), involvement in de novo purine biosynthesis and over-expression in fetal DS brain postmortem samples. GARS–AIRS–GART regions important for structure–function were screened for mutations that might alter protein levels in DS patients. Mutation screening relied on multiplex/singleplex PCR-based amplification of genomic targets followed by amplicon size determination/fingerprinting. Serum protein samples were resolved by SDS-PAGE and immunoblotted with a GARS–AIRS–GART monoclonal antibody. No variation in amplicon size/fingerprints was observed in regions encoding the ATP-binding, active site residues of GARS, the structurally important glycine-rich loops of AIRS, substrate-binding, flexible and folate-binding loops of GART or the poly-adenylation signal sequences. The de novo occurrence or inheritance of large insertion/deletion/rearrangement-type mutations is therefore excluded. Immunoblots show presence of GARS–AIRS–GART protein in all patient samples, with no change in expression levels with respect to either sex or developmental age.

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Acknowledgments

Debarati Ghosh and Disha Banerjee are recipients of Senior Research Fellowships from CSIR grant 27(0131)/04/EMR-II and DST grant SR/SO/HS-59/2003 awarded to Dr. Krishnadas Nandagopal.

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Authors and Affiliations

  1. Manovikas Biomedical Research and Diagnostic Centre, 482 Madudah, Plot I-24, Sector J, Eastern Metropolitan Bypass, Kolkata, 700 107, India

    Disha Banerjee, Debarati Ghosh & Krishnadas Nandagopal

  2. Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, 482 Madudah, Plot I-24, Sector J, Eastern Metropolitan Bypass, Kolkata, 700 107, India

    Anindita Chatterjee, Swagata Sinha & Krishnadas Nandagopal

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  1. Disha Banerjee
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  2. Debarati Ghosh
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Correspondence to Krishnadas Nandagopal.

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Banerjee, D., Ghosh, D., Chatterjee, A. et al. No Evidence for Mutations that Deregulate GARS–AIRS–GART Protein Levels in Children with Down Syndrome. Ind J Clin Biochem 27, 46–51 (2012). https://doi.org/10.1007/s12291-011-0183-6

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  • DOI: https://doi.org/10.1007/s12291-011-0183-6

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