Geneimprint
Luedi, et. al. Genome Res. (Dec 2007) Fulltext Suppl
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30 November 2007: Genomic imprinting is an epigenetic form of gene regulation that results in only the copy inherited from the mother or father to function. (Jirtle and Weidman 2007). The phenomenon of imprinting evolved about 150 M years ago in a common ancester to mammals that have live birth - the Therian mammals (Marsupials and Eutherians) (Killian et al. 2000).
Imprinted genes are at high risk for envolvement in diseases since a single genetic mutation or an environmentally-induced epigenetic change can alter their function. Imprinting deregulation results in developmental disorders such as Beckwith-Wiedemann, Angelman and Prader-Willi syndromes. Additionally, the incidence of these disorders is increased in humans conceived by assisted reproductive technology (ART) because of detrimental changes in imprinted gene regulation (Niemitz and Feinberg 2004).
A genome-wide search for imprinted genes in the human genome, with the use of computer-learning algorithms, resulted in the identification of 156 novel candidate imprinted genes (Luedi et al. 2007). Interestingly, humans are predicted to not only contain fewer imprinted genes than mice, but the repertoire of these genes in humans is also markedly different than that in mice (Luedi et al. 2007, Luedi et al. 2005). Consequently, despite the immense popularity of mice as models for human ailments, they may not be a suitable choice for studying diseases resulting principally from the epigenetic deregulation of imprinted genes, or for assessing human risk from environmental factors that alter the epigenome.
Two of the candidate imprinted genes identified were subsequently shown experimentally to be imprinted: KCNK9 is predominantly expressed in the cerebellum of the brain, is a known oncogene, and may be involved in bipolar disorder and epilepsy, while DLGAP2 may play a role in the molecular organization of synapses and in neuronal cell signaling, and is a candidate bladder cancer tumor suppressor. By mapping these candidate imprinted gene onto the disease landscape defined by linkage analyses, we are poised to determine the importance of imprinting deregulation in the etiology of the major complex human diseases and neurological disorders that plague mankind.
The hypothesis of fetal origins of adult disease proposes that early developmental exposures involve epigenetic modifications, such as DNA methylation, that influence adult disease susceptibility (Jirtle and Skinner). Read more...
An epigenetic change alters the phenotype without changing the genotype. As a result of their unique genetic make-up, imprinted genes act as nodes of susceptibility for asthma, cancer, diabetes, obesity and many behavioral and developmental disorders - a list that is surprisingly long given the limited number of imprinted genes identified so far. Read more...
Genistein, the major phytoestrogen in soy, is linked to diminished female reproductive performance and to cancer chemoprevention and decreased adipose deposition. Dietary genistein may also play a role in the decreased incidence of cancer in Asians compared with Westerners, as well as increased cancer incidence in Asians immigrating to the United States. Read more...
