Homeobox protein Hox-D13 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''HOXD13''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
This gene belongs to the
homeobox
A homeobox is a Nucleic acid sequence, DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of ...
family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in
morphogenesis
Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...
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.
Changes in the expression of the Hoxd13 gene in early lobe-finned fish may have also contributed to the evolution of the tetrapod limb. 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. A number of similar studies conducted with a range of animals, including catsharks and marsupials, 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
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
syndactyly
Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, but is an unusual condition in humans. The term is .
Classification
Syndactyly can be simple or complex.
* In simple syndactyly, adja ...
and
brachydactyly
Brachydactyly () is a medical term denoting the presence of abnormally short digits (fingers or toes) at birth. The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an inherited, dominant t ...
, including
brachydactyly type D
Brachydactyly type D, also known as murderer's thumb, stubbed thumb, spoon thumb, or short thumb, is a genetic trait recognised by a thumb being relatively short and round with an accompanying wider Nail (anatomy), nail bed. The distal phalanx of ...
("club thumb"),
brachydactyly type E,
syndactyly type 5 and
synpolydactyly
Synpolydactyly (SPD) is a joint presentation of syndactyly (fusion of digits) and polydactyly (production of supernumerary digits).Goodman FR, Mundlos S, Muragaki Y, et al. Synpolydactyly phenotypes correlate with size of expansions in hoxd13 poly ...
type 1.
See also
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Homeobox
A homeobox is a Nucleic acid sequence, DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of ...
References
Further reading
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External links
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Transcription factors
{{gene-2-stub