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Final draft for December 4th

Homeotic genes in humans

In humans, there are several families of homeotic genes that are involved in development . These homeotic genes contain a DNA domain called a homeobox. Homeobox gene families in humans include the HOX, PAX , EMX, OTX, and MSX families. HOX genes begin to be expressed during gastrulation. Humans have 39 HOX genes encoded in four clusters: HOXA, HOXB, HOXC, and HOXD. There are only two known human mutations in HOX genes. These mutations occur in HOXD13 and HOXA13. The HOXD13 mutation, discovered in 1996, causes synpolydactyly and the HOXA13 mutation, discovered in 1997, causes hand-foot-genital syndrome. Both these genes lie near the 5' end of their gene clusters and play important roles in distal limb and lower uro/genital tract development.

In synpolydactyly, the gene locus affected is on chromosome 2q31 where the HOXD13 gene cluster is located. In affected individuals, the polypeptide chain of exon 1 of HOXD13 contains 7,8, or 10 more amino acid residues. Synpolydactyly can also be caused by intragenic deletion in the homeobox or exon 1 region of the HOXD13 gene.

Hand-foot-genital syndrome occurs when there is a mutation to the HOXA13 gene locus. There are five identified mutations in HOX genes that cause hand-foot-genital syndrome which fall under nonsense mutations, missense mutations or repeat additions.

Homeobox genes are also expressed in tissues during adult life and there is a connection between the miss-expression of these genes and oncogenisis . In kidney tumors, HOX genes have been found to be turned off/on or have different transcripts. Missexpression of HOX genes has been found in colon cancers, while certain lung cancers correlate with turning off HOX genes. The homeobox family of PAX genes also have a known link to oncogenesis.

Homeotic genes in plants

Development of plants is also sculpted by homeotic genes that influence the expression of genes that differentiate flower organs. Homeotic genes in plants, like in animals and insects, switch developmental pathways on or off and influence structures. Most analysis of homeotic genes in plants has been done in Antirrhinum majus and arabidopsis thaliana because of the ease with which they can be worked with and genetically manipulated. The ABC model of development is used to describe how different combinations of A, B, and C genes influence the development of different parts of the plant. In different plants, different homeotic genes code for A,B, or C. All ABC genes share a highly conserved DNA sequence called a MADS box. The MADS box encodes a DNA binding domain where transcription factors can bind.

An example of a homeotic gene found in plants are deficiens, found in Antirrhinum majus. Deficiens are expressed in the flowers of plants, and expression is heavily constant throughout the stages of plant development. Mutations in the gene cause the transformation of petals into sepals and stamina into carpels. Deficiens are homologous to SRF, a regulatory protein found in mammals.

Homeotic genes in Drosophila melanogaster

Drosophila melanogaster is a common model organism used for the study of homeotic genes and their mutations. Drosophila is a model organism because mutations are usually remarkable and occur very early in larvae development. Through isolating mutations, researchers have mapped out the locations of these genes and found that most occur within two gene clusters. These two clusters of homeotic genes are know as the bithorax and antennapedia complexes (BX-C and ANT-C respectively). The BX-C gene cluster controls the identity of two thirds of drosophila development through the regulation of three genes. The ANT-C gene cluster controls five homeotic genes as well as several non-homeotic genes involved in larvae segmentation. When researchers studied the genes in BX-C and ANT-C they found all the genes contained a DNA sequence called a homeobox. The discovery of homeobox domains allowed researchers to isolate genes based on function and homology both in drosophila and other organisms.