DYX1C1
| DNAAF4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | DNAAF4, CILD25, DYX1, DYXC1, EKN1, RD, DYX1C1, dyslexia susceptibility 1 candidate 1, dynein axonemal assembly factor 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 608706; MGI: 1914935; HomoloGene: 12173; GeneCards: DNAAF4; OMA:DNAAF4 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Dyslexia susceptibility 1 candidate gene 1 protein is a protein that in humans is encoded by the DYX1C1 gene.[5][6] This protein contains 420 amino acids with 3 tetratricopeptide repeat (TPR) domains, thought to mediate protein–protein interactions. It is a protein-coding gene strongly associated with susceptibility to developmental dyslexia, a learning disorder that affects reading ability in otherwise typically developing individuals.[5]
Gene
[edit]Although the gene does not show strong homology to many well-characterized proteins, it is highly conserved across species, with significant similarity between humans, mice, and nonhuman primates, indicating an important biological function.[5]
Structure
[edit]The DYX1C1 protein consists of approximately 420 amino acids and is characterized by the presence of three tetratricopeptide repeat (TPR) domains, which are structural motifs known to facilitate protein–protein interactions. [5] These domains suggest that DYX1C1 functions as part of larger molecular complexes, potentially playing a role in regulating cellular processes critical for brain development.[5]
Function
[edit]The DYX1C1 gene play a crucial role in the function of motile cilia that are on the surface of cells in eukaryotes that beat in sense of rhythmic waves to move fuilds,mucus, or cells across tissue surfaces.[7] Research shows that when this gene is disrupted (function has been changed) the leading to defects in the inner and out dynein arms[7] this is required for ciliary motion resulting in conditions like primary ciliary dyskinesia (PCD).[7]Evidence from mice, zebrafish, and humans demonstrates that DYX1C1 acts in the cytoplasm as a dynein axonemal assembly factor, interacting with chaperone proteins and other assembly factors to ensure cilia are built correctly. [7]Without this function, cilia may still form structurally but are immotile, leading to symptoms such as chronic respiratory disease, laterality defects, and infertility.[7] The genes DYX1C1 is a candidate genes linked to dyslexia, and their primary shared function is in neuronal migration during brain development.[8] This means they help guide neurons to their correct positions in the developing neocortex, which is essential for proper brain organisation and function.[8] Specifically, DYX1C1 is required for neurons to transition out of an early “multipolar” stage and move to their final locations; its C-terminal region is critical for this role.[8] In addition to its role in the brain, DYX1C1 also has a separate function in cilia biology, where it helps assemble dynein arms needed for ciliary movement.[8]
A key finding is that DYX1C1 is not only linked to neuronal migration and dyslexia risk, but also plays an important role in the formation and function of motile cilia, which are structures responsible for moving fluids in the brain, airways, and developing embryo. [9]The study shows that DYX1C1 interacts with other cilia-related proteins (such as CPAP and DCDC2) and is involved in cytoplasmic processes that help assemble dynein motor arms required for ciliary movement.[9] When this gene is disrupted, it leads to defects in ciliary motility, causing developmental issues such as abnormal left-right body patterning, hydrocephalus, and impaired fluid flow.[9] Overall, the function of DYX1C1 is best described as a regulator of cilia assembly and activity, linking cellular structural machinery to both neurological development and broader developmental biology.[9]
Clinical significance
[edit]A mutation in the DYX1C1 gene has been associated with deficits in reading ability (dyslexia).[5][10]
Testing
[edit]Testing DYX1C1 not only if the protein is functional in case so testing the most effective approaches for testing the role of DYX1C1 because it combines a family-based genetic design with precise cognitive measurements and robust statistical analysis.[11] By using nuclear families with a diagnosed dyslexic proband, the researchers reduce population stratification bias and ensure that genetic transmission patterns are accurately captured.[11] The use of direct DNA sequencing for key DYX1C1 markers (−3GA and 1249GT) strengthens the reliability of variant detection.[11]
References
[edit]- 1 2 3 GRCh38: Ensembl release 89: ENSG00000256061 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000092192 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 1 2 3 4 5 6 Taipale M, Kaminen N, Nopola-Hemmi J, Haltia T, Myllyluoma B, Lyytinen H, et al. (October 2003). "A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain". Proceedings of the National Academy of Sciences of the United States of America. 100 (20): 11553–11558. doi:10.1073/pnas.1833911100. PMC 208796. PMID 12954984.
- ↑ "Entrez Gene: DYX1C1 dyslexia susceptibility 1 candidate 1".
- 1 2 3 4 5 Tarkar A, Loges NT, Slagle CE, Francis R, Dougherty GW, Tamayo JV, et al. (September 2013). "DYX1C1 is required for axonemal dynein assembly and ciliary motility". Nature Genetics. 45 (9): 995–1003. doi:10.1038/ng.2707. PMC 4000444. PMID 23872636.
- 1 2 3 4 Wang Y, Paramasivam M, Thomas A, Bai J, Kaminen-Ahola N, Kere J, et al. (December 2006). "DYX1C1 functions in neuronal migration in developing neocortex". Neuroscience. 143 (2): 515–522. doi:10.1016/j.neuroscience.2006.08.022. PMID 16989952.
- 1 2 3 4 Bieder A, Chandrasekar G, Wason A, Erkelenz S, Gopalakrishnan J, Kere J, et al. (May 2023). "Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2". BMC Molecular and Cell Biology. 24 (1) 20. doi:10.1186/s12860-023-00483-4. PMC 10224228. PMID 37237337.
- ↑ Bates TC, Lind PA, Luciano M, Montgomery GW, Martin NG, Wright MJ (November 2009). "Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation". Molecular Psychiatry. 15 (12): 1190–1196. doi:10.1038/mp.2009.120. PMID 19901951.
- 1 2 3 Marino C, Mascheretti S, Riva V, Cattaneo F, Rigoletto C, Rusconi M, et al. (January 2011). "Pleiotropic effects of DCDC2 and DYX1C1 genes on language and mathematics traits in nuclear families of developmental dyslexia". Behavior Genetics. 41 (1): 67–76. doi:10.1007/s10519-010-9412-7. PMC 3939676. PMID 21046216.
Further reading
[edit]- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Brkanac Z, Chapman NH, Matsushita MM, Chun L, Nielsen K, Cochrane E, et al. (June 2007). "Evaluation of candidate genes for DYX1 and DYX2 in families with dyslexia". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 144B (4): 556–560. doi:10.1002/ajmg.b.30471. PMID 17450541. S2CID 43864328.
- Cope NA, Hill G, van den Bree M, Harold D, Moskvina V, Green EK, et al. (March 2005). "No support for association between dyslexia susceptibility 1 candidate 1 and developmental dyslexia". Molecular Psychiatry. 10 (3): 237–238. doi:10.1038/sj.mp.4001596. PMID 15477871. S2CID 1777791.
- Marino C, Citterio A, Giorda R, Facoetti A, Menozzi G, Vanzin L, et al. (October 2007). "Association of short-term memory with a variant within DYX1C1 in developmental dyslexia". Genes, Brain, and Behavior. 6 (7): 640–646. doi:10.1111/j.1601-183X.2006.00291.x. PMID 17309662.
- Scerri TS, Fisher SE, Francks C, MacPhie IL, Paracchini S, Richardson AJ, et al. (November 2004). "Putative functional alleles of DYX1C1 are not associated with dyslexia susceptibility in a large sample of sibling pairs from the UK". Journal of Medical Genetics. 41 (11): 853–857. doi:10.1136/jmg.2004.018341. PMC 1735619. PMID 15520411.
- Wigg KG, Couto JM, Feng Y, Anderson B, Cate-Carter TD, Macciardi F, et al. (December 2004). "Support for EKN1 as the susceptibility locus for dyslexia on 15q21". Molecular Psychiatry. 9 (12): 1111–1121. doi:10.1038/sj.mp.4001543. PMID 15249932.
- Ylisaukko-Oja T, Peyrard-Janvid M, Lindgren CM, Rehnström K, Vanhala R, Peltonen L, et al. (January 2005). "Family-based association study of DYX1C1 variants in autism". European Journal of Human Genetics. 13 (1): 127–130. doi:10.1038/sj.ejhg.5201272. PMID 15470369.