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Deep sequencing reveals 50 novel genes for recessive cognitive disorders

Item Type:Article
Title:Deep sequencing reveals 50 novel genes for recessive cognitive disorders
Creators Name:Najmabadi, H. and Hu, H. and Garshasbi, M. and Zemojtel, T. and Abedini, S.S. and Chen, W. and Hosseini, M. and Behjati, F. and Haas, S. and Jamali, P. and Zecha, A. and Mohseni, M. and Puettmann, L. and Vahid, L.N. and Jensen, C. and Moheb, L.A. and Bienek, M. and Larti, F. and Mueller, I. and Weissmann, R. and Darvish, H. and Wrogemann, K. and Hadavi, V. and Lipkowitz, B. and Esmaeeli-Nieh, S. and Wieczorek, D. and Kariminejad, R. and Firouzabadi, S.G. and Cohen, M. and Fattahi, Z. and Rost, I. and Mojahedi, F. and Hertzberg, C. and Dehghan, A. and Rajab, A. and Banavandi, M.J.S. and Hoffer, J. and Falah, M. and Musante, L. and Kalscheuer, V. and Ullmann, R. and Kuss, A.W. and Tzschach, A. and Kahrizi, K. and Ropers, H.H.
Abstract:Common diseases are often complex because they are genetically heterogeneous, with many different genetic defects giving rise to clinically indistinguishable phenotypes. This has been amply documented for early-onset cognitive impairment, or intellectual disability, one of the most complex disorders known and a very important health care problem worldwide. More than 90 different gene defects have been identified for X-chromosome-linked intellectual disability alone, but research into the more frequent autosomal forms of intellectual disability is still in its infancy. To expedite the molecular elucidation of autosomal-recessive intellectual disability, we have now performed homozygosity mapping, exon enrichment and next-generation sequencing in 136 consanguineous families with autosomal-recessive intellectual disability from Iran and elsewhere. This study, the largest published so far, has revealed additional mutations in 23 genes previously implicated in intellectual disability or related neurological disorders, as well as single, probably disease-causing variants in 50 novel candidate genes. Proteins encoded by several of these genes interact directly with products of known intellectual disability genes, and many are involved in fundamental cellular processes such as transcription and translation, cell-cycle control, energy metabolism and fatty-acid synthesis, which seem to be pivotal for normal brain development and function.
Keywords:Brain, Cell Cycle, Cognition Disorders, Consanguinity, DNA Mutational Analysis, Essential Genes, Exons, Gene Regulatory Networks, High-Throughput Nucleotide Sequencing, Homozygote, Intellectual Disability, Metabolic Networks and Pathways, Mutation, Organ Specificity, Recessive Genes, Synapses
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:478
Number:7367
Page Range:57-63
Date:6 October 2011
Official Publication:https://doi.org/10.1038/nature10423
PubMed:View item in PubMed

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