Biology:HOXD13
 Generic protein structure example |
Homeobox protein Hox-D13 is a protein that in humans is encoded by the HOXD13 gene.[1][2][3] This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms.
Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9–11 genes arranged in tandem. HOXD13 is the first of several HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The product of the mouse Hoxd13 gene plays a role in axial skeleton development and forelimb morphogenesis.[4]
Changes in the expression of the Hoxd13 gene in early lobe-finned fish may have also contributed to the evolution of the tetrapod limb.[5] Experiments investigating the impact of 5′ Hoxd overexpression in zebrafish embryos observed modified development of distal fin structures, resulting in increased proliferation, distal expansion of cartilage tissue and fin fold reduction.[6] A number of similar studies conducted with a range of animals, including catsharks[7] and marsupials,[8] lend further credibility to the role of the Hoxd13 gene in the fin-to-limb transition.
Clinical significance
Mutations in HOXD13 can cause several types of autosomal dominant syndactyly and brachydactyly, including brachydactyly type D ("club thumb"), brachydactyly type E, syndactyly type 5 and synpolydactyly type 1.[9]
See also
References
- ↑ "The human HOX gene family". Nucleic Acids Research 17 (24): 10385–402. December 1989. doi:10.1093/nar/17.24.10385. PMID 2574852.
- ↑ "Nomenclature for human homeobox genes". Genomics 7 (3): 460. July 1990. doi:10.1016/0888-7543(90)90186-X. PMID 1973146.
- ↑ "Entrez Gene: HOXD13 homeobox D13". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3239.
- ↑ "A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse". Development 122 (4): 1175–85. April 1996. doi:10.1242/dev.122.4.1175. PMID 8620844. http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=8620844.
- ↑ "Making limbs from fins". Developmental Cell 23 (6): 1121–2. December 2012. doi:10.1016/j.devcel.2012.11.011. PMID 23237946.
- ↑ "Hoxd13 contribution to the evolution of vertebrate appendages". Developmental Cell 23 (6): 1219–29. December 2012. doi:10.1016/j.devcel.2012.10.015. PMID 23237954.
- ↑ "Key genetic event underlying fin-to-limb evolution: Study of catsharks reveals how alterations in the expression, function of certain genes in limb buds underlie evolution of fish fins to limbs" (in en). https://www.sciencedaily.com/releases/2015/08/150818102910.htm.
- ↑ "HOXA13 and HOXD13 expression during development of the syndactylous digits in the marsupial Macropus eugenii". BMC Developmental Biology 12 (1): 2. January 2012. doi:10.1186/1471-213X-12-2. PMID 22235805.
- ↑ "OMIM Entry - * 142989 - HOMEOBOX D13; HOXD13". https://www.omim.org/entry/142989.
Further reading
- "Molecular models for vertebrate limb development". Cell 90 (6): 979–90. September 1997. doi:10.1016/S0092-8674(00)80364-5. PMID 9323126.
- "Limb malformations and the human HOX genes". American Journal of Medical Genetics 112 (3): 256–65. October 2002. doi:10.1002/ajmg.10776. PMID 12357469.
- "Vertebrate homeobox gene nomenclature". Cell 71 (4): 551–3. November 1992. doi:10.1016/0092-8674(92)90588-4. PMID 1358459.
- "EVX2, a human homeobox gene homologous to the even-skipped segmentation gene, is localized at the 5' end of HOX4 locus on chromosome 2". Genomics 10 (1): 43–50. May 1991. doi:10.1016/0888-7543(91)90482-T. PMID 1675198.
- "Localization of the syndactyly type II (synpolydactyly) locus to 2q31 region and identification of tight linkage to HOXD8 intragenic marker". Human Molecular Genetics 4 (8): 1453–8. August 1995. doi:10.1093/hmg/4.8.1453. PMID 7581388.
- "Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13". Science 272 (5261): 548–51. April 1996. doi:10.1126/science.272.5261.548. PMID 8614804. Bibcode: 1996Sci...272..548M.
- "Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families". Human Molecular Genetics 5 (7): 945–52. July 1996. doi:10.1093/hmg/5.7.945. PMID 8817328.
- "Polyalanine expansion in synpolydactyly might result from unequal crossing-over of HOXD13". Science 275 (5298): 408–9. January 1997. doi:10.1126/science.275.5298.408. PMID 9005557.
- "Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract". Proceedings of the National Academy of Sciences of the United States of America 94 (14): 7458–63. July 1997. doi:10.1073/pnas.94.14.7458. PMID 9207113. Bibcode: 1997PNAS...94.7458G.
- "Deletions in HOXD13 segregate with an identical, novel foot malformation in two unrelated families". American Journal of Human Genetics 63 (4): 992–1000. October 1998. doi:10.1086/302070. PMID 9758628.
- "Clustering of two fragile sites and seven homeobox genes in human chromosome region 2q31-->q32.1". Cytogenetics and Cell Genetics 90 (1–2): 151–3. 2000. doi:10.1159/000015651. PMID 11060466.
- "Creation of genome-wide protein expression libraries using random activation of gene expression". Nature Biotechnology 19 (5): 440–5. May 2001. doi:10.1038/88107. PMID 11329013.
- "A 117-kb microdeletion removing HOXD9-HOXD13 and EVX2 causes synpolydactyly". American Journal of Human Genetics 70 (2): 547–55. February 2002. doi:10.1086/338921. PMID 11778160.
- "Complete mutation analysis panel of the 39 human HOX genes". Teratology 65 (2): 50–62. February 2002. doi:10.1002/tera.10009. PMID 11857506.
- "Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13". Journal of Medical Genetics 39 (11): 852–6. November 2002. doi:10.1136/jmg.39.11.852. PMID 12414828.
- "An I47L substitution in the HOXD13 homeodomain causes a novel human limb malformation by producing a selective loss of function". Development 130 (8): 1701–12. April 2003. doi:10.1242/dev.00396. PMID 12620993.
External links
- HOXD13+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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