Genomic imprinting affects a subset of genes in mammals and results in a monoallelic, parental-specific expression pattern. Most of these genes are located in clusters that are regulated through the use of insulators or long noncoding RNAs lncRNAs. To distinguish the parental alleles, imprinted genes are epigenetically marked in gametes at imprinting control elements through the use of DNA methylation at the very least. Imprinted gene expression is subsequently conferred through lncRNAs, histone modifications, insulators, and higher-order chromatin structure.
Such imprints are maintained after fertilization through these mechanisms despite extensive reprogramming of the mammalian genome. Genomic imprinting is an excellent model for understanding mammalian epigenetic regulation. Mammals are diploid organisms whose cells possess two matched sets of chromosomes, one inherited from the mother and one from the father.
Thus, mammals have two copies of every gene. Normally both the maternal and paternal copy of each gene has the same potential to be active in any cell. Genomic imprinting is an epigenetic mechanism that changes this potential because it restricts the expression of a gene to one of the two parental chromosomes. It is a phenomenon displayed by only a few hundred of the approximately 25, genes in our genome, the majority being expressed equally when Human imprinting during dating from either parent.
Genomic imprinting affects both male and female offspring and is therefore a consequence of parental inheritance, not of sex. As an example of what is meant by this, an imprinted gene that is active on a maternally inherited chromosome will be active on the maternal chromosome and silent on the paternal chromosome in all males and females.
In contrast, nonimprinted genes will be expressed from both parental gene copies in a diploid cell. To understand the concept of genomic imprinting it is important to distinguish between imprinted genes and those showing apparent parental-specific expression because of unequal parental genetic contribution to the embryo. Examples of unequal parental genetic contribution include Y chromosome—linked genes present only in males, genes that escape X inactivation in females producing a double dose of X-linked gene products compared with malesmitochondrial genes contributed mainly by the maternal parent, and messenger RNAs mRNAs and proteins present only in the sperm or egg cytoplasm.
Many features of genomic imprinting in mammals make it a fascinating biological problem in postgenomic times. It is intriguing that the subset of genes subject to genomic imprinting largely code for factors regulating embryonic and neonatal growth.
Thus, it is likely that genomic imprinting evolved to play a specific role in mammalian reproduction. It is also providing clues as to a possible evolutionary response to parental conflict, to the adaptation of the maternal parent to an internal reproduction system, and, perhaps, providing a glimpse of the way the mammalian genome protects itself against invading DNA sequences. Genomic imprinting is an intellectually challenging phenomenon, not least because it raises the question of why a diploid would evolve a silencing system that forsakes the advantages of the diploid state.
At this stage of our knowledge, genomic imprinting does not appear to be widespread among the four eukaryotic kingdoms that include Protista, Fungi, Plants, and Animals. However, it does exist, in a possibly related form, in two invertebrate arthropods—Coccidae and Sciaridae, and in the endosperm of some seed-bearing plants, such as maize and Arabidopsis.
This distribution indicates that genomic imprinting arose independently at least three times during the evolution of life. Surprisingly, despite this predicted independent evolution of genomic imprinting, some similarities among the imprinting mechanism are emerging. It is likely that this reflects conservation "Human imprinting during dating" basic epigenetic regulatory mechanisms that underlie both genomic imprinting and normal gene regulation. The presence of genomic imprinting in mammals has considerable medical, societal, and intellectual implications in terms of 1 the clinical management of genetic traits and diseases, 2 the capacity to control human and animal breeding by assisted reproductive technologies, and 3 the progress of biotechnology and postgenomic medical research.
Any modern day discussion of genetic problems, whether in research or medicine, must consider if a gene shows a biparental i. Despite the importance of genomic Human imprinting during dating to human health and well-being, it is surprising that widespread acceptance of its existence and significance did not happen until the early nineties three genes were unequivocally shown to display parental-specific expression in mice.
Parental-specific behavior of whole chromosomes had been observed in cytogenetic studies of chromosomes in Arthropods as early as the s Chandra and Nanjundiah Chromosomal imprinting of the mammalian X chromosome was also noted, which leads to paternal-specific inactivation of one of the two X chromosomes in all cells of female marsupials and the extraembryonic tissues of the mouse Cooper et al.
During the same period, classical geneticists were generating mouse mutants carrying chromosomal translocations that laid the foundation for the observation of imprinted gene expression. Instead, offspring who received the Hairpin-tail deletion from a maternal parent were increased in size and died midway through embryonic development, whereas paternal transmission of the genetically identical chromosome produced viable and fertile mice Fig.
It is notable with hindsight that in spite of the previously published description of imprinted X-chromosome inactivation in mammals, the favored interpretation of these genetic translocation and deletion experiments was not that the regions contained imprinted genes, but that genes on these autosomes primarily acted in haploid egg or sperm to modify proteins used later in embryonic development.
Mouse models to study genomic imprinting that allow the maternal and paternal chromosome to be distinguished. Mammals are diploid and inherit a complete chromosome set from the maternal and paternal parent.
However, mice can be generated that 1 inherit two copies of a chromosome pair from one parent and no copy from the other parent known as UPD2 inherit Human imprinting during dating partial chromosomal deletion from one parent and a wild-type chromosome from the other parent, and 3 inherit chromosomes carrying single-nucleotide polymorphisms known as SNPs from one parent and a wild-type chromosome from the other parent.
Offspring with UPDs or deletions are likely to display lethal phenotypes, whereas SNPs will allow the production of viable offspring. A major step forward in establishing the existence of genomic imprinting in mammals came several years later with the development of an improved nuclear transfer technology being used to test the possibility of generating diploid uniparental embryos solely from mouse egg nuclei. The nuclear transfer technique took a donor male or female pronucleus from a newly fertilized egg and used a fine micropipette to place it inside a host fertilized egg from which either the maternal or paternal pronucleus had been removed.
This regenerated diploid embryos, but with two "Human imprinting during dating" or two paternal genomes known, respectively, as gynogenetic and androgenetic embryos; Fig. The technique was first used to show that nuclei from fertilized Hairpin-tail mutant embryos could not be rescued when transferred into a wild-type host egg. This provided proof that the embryonic genome, and not the oocyte cytoplasm, carried the Hairpin-tail defect.
It also Human imprinting during dating the suggestion that genes on the maternal and paternal copy of chromosome 17 functioned differently during embryonic development McGrath and Solter b. Subsequently, nuclear transfer was used to show that embryos, reconstructed from two maternal pronuclei known as gynogenetic embryos or two paternal pronuclei androgenetic embryosfailed to survive; whereas only embryos reconstructed from one maternal and one paternal pronucleus produced viable and fertile offspring McGrath and Solter a ; Surani et al.
This work overturned a previous claim that uniparental mice could develop to adulthood Hoppe and Illmensee Gynogenetic embryos at the time of death were defective in extraembryonic tissues that contribute to the placenta, whereas androgenetic embryos were defective in embryonic tissue.
These outcomes led to the hypothesis that embryonic development required imprinted genes expressed from the maternal genome, whereas the paternal genome expressed imprinted genes required for extraembryonic development Barton et al.
Subsequent identification of imprinted genes in the mouse did not confirm a bias in the function of imprinted genes, but indicated that the observed differences between gynogenetic and androgenetic embryos may be explained by a dominant effect of one or a few imprinted genes. A maternal and paternal genome are needed for mammalian reproduction. Gynogenetic and androgenetic embryos were lethal at early embryonic stages.
Only reconstituted embryos that received both a maternal and paternal nucleus wild-type survived to produce living young. These experiments show the necessity for both the maternal and paternal genome in mammalian reproduction, and indicate the two parental genomes "Human imprinting during dating" different sets of genes needed for complete embryonic development.
The nuclear transfer experiments, combined with supporting data from mouse genetics, provided convincing evidence that both parental genomes were required for embryogenesis in mice, laying Human imprinting during dating strong foundation for the existence of genomic imprinting in mammals Fig. This further strengthened the argument for parental-specific gene expression in mammals Cattanach and Kirk In addition, human data strongly indicated that some genetic conditions, most notably the Prader—Willi syndrome, which appears to arise exclusively by paternal transmission, could best be explained by parental-specific gene expression Reik Further clues came from experiments applying the newly developed technology for making transgenic mice by microinjecting gene sequences into a fertilized mouse egg.
This was often beset by the problem of DNA methylation unexpectedly inducing silencing of the transgene in somatic tissues. Some transgenes even showed parental-specific differences in their ability to acquire DNA methylation, adding weight to the argument that parental chromosomes behave differently.
This normally followed the pattern that maternally transmitted transgenes were methylated whereas paternally transmitted transgenes were not. However, only in a few cases did DNA methylation differences correlate with parental-specific expression. This includes a high susceptibility Human imprinting during dating strain-specific background effects, an inability to maintain imprinted expression at different chromosomal integration sites, and a requirement for foreign DNA sequences to produce the imprinted effect Chaillet et al.
Despite the wealth of supportive data, final proof of the existence of genomic imprinting in mammals depended on the identification of genes showing imprinted parental-specific expression. This occurred in when three imprinted mouse genes were described. This gene was later shown to explain the overgrowth phenotype of the Hairpin-tail mutant mouse Barlow et al.
A few months later, the Igf2 gene was identified as a paternally expressed imprinted gene DeChiara et al.