Genomic imprinting

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Genomic imprinting (engl. Genomic imprinting , genetic imprinting ) refers to the phenomenon that the expression of genes may depend on from which individual parent the allele originates.

properties

Genomic imprinting does not yet occur in the classical Mendelian inheritance , but was only discovered later. In the case of genes that are subject to genomic imprinting (imprinted genes), either only the version from the mother or only the version from the father is active. The genes therefore have a parental genomic imprint. Imprinting is based on epigenetic modifications of the DNA , which is retained in the germ cells. The base sequence is not changed. Due to this epigenetic imprint, one of the two parental alleles of the imprinted gene is active and the other is inactive. These parental imprints are partially erased in the early germ cells of each individual and re-established according to gender - the epigenetic coding of imprinted genes is thus reversible . Significant differences to "classic" inheritance are e.g. B. the parent-dependent inheritance of the activity state of a gene, the reversibility of this state and the independence of the imprint from the genetic code .

The epigenetic information that is imprinted on the special allele can essentially only assume two states: on or off. The information content of the allele, the DNA sequence , is not changed.

In simplified terms, genomic imprinting can also be described as parent-specific ( maternal or paternal ) expression of a genetic predisposition. The modification can take place during the germ cell development ( spermatogenesis and oogenesis ) or in the later development and influence this. In mammals, genomic imprinting is controlled by CTCF-dependent insulators and long non-coding RNA . A certain allele (gene variant) is only expressed if, depending on the case, it comes from either the female (maternal) or the male (paternal) parent.

Certain mutant alleles subject to genomic imprinting appear to be inherited recessively when inherited from the mother, but dominant when inherited from the father; the dominance of other such alleles appears to be exactly the opposite of the sex of the inheriting parent. This phenomenon has been best studied in mammals as well as humans, and the mechanism on which the imprint is based is a specific epigenetic modification (often methylation of CpG islands ) of the DNA at certain regulatory sites in imprinted genes. As a result of this DNA methylation , the gene is shut down ( gene silencing ). The modifications are first deleted when passing through the germ line ( meiosis ), then rebuilt in a gender-specific manner (either only maternal or paternal).

As of 2019, there are 260 known genes with genomic imprinting in mice and 228 in humans.

Organisms with imprinting

Imprinting-like phenomena have been observed independently in mammals (but not in monotones ) and flowering plants . Whether the mechanism of imprinting is the same is currently unknown, but all of these phenomena lead to a functionally hemizygous state in which only one allele is active on the affected gene locus .

Examples

Dozens of genes are known that are subject to genomic imprinting (e.g. H19 and CDKN1c: active allele maternal, or Xist and Igf2 : active allele paternal). Some genetic diseases in humans are associated with (faulty) imprinting, such as Beckwith-Wiedemann syndrome , Angelman syndrome or Prader-Willi syndrome . The involvement of genomic imprinting is also significant in the development of some types of cancer (e.g. Wilms tumor ).

Genomic imprinting is believed to be involved in the problems of in vitro fertilization (IVF) using intracytoplasmic sperm injection ICSI and in the cloning of mammals.

literature

  • Carmen Sapienza: Parental imprinting of genes, Scientific American, October 1990

Individual evidence

  1. ↑ BT Adalsteinsson, AC Ferguson-Smith: Epigenetic control of the genome-lessons from genomic imprinting. In: Genes. Volume 5, Number 3, 2014, pp. 635-655, ISSN  2073-4425 . doi : 10.3390 / genes5030635 . PMID 25257202 . PMC 4198922 (free full text).
  2. ^ RN Plasschaert, MS Bartolomei: Genomic imprinting in development, growth, behavior and stem cells. In: Development. Volume 141, Number 9, May 2014, pp. 1805-1813, ISSN  1477-9129 . doi : 10.1242 / dev.101428 . PMID 24757003 . PMC 3994769 (free full text).
  3. ^ EJ Radford, SR Ferrón, AC Ferguson-Smith: Genomic imprinting as an adaptative model of developmental plasticity. In: FEBS letters. Volume 585, Number 13, July 2011, pp. 2059-2066, ISSN  1873-3468 . doi : 10.1016 / j.febslet.2011.05.063 . PMID 21672541 .
  4. ↑ MS Bartolomei, AC Ferguson-Smith: Mammalian genomic imprinting. In: Cold Spring Harbor perspectives in biology. Volume 3, Number 7, July 2011, pp., ISSN  1943-0264 . doi : 10.1101 / cshperspect.a002592 . PMID 21576252 . PMC 3119911 (free full text).
  5. ↑ V. Tucci, AR Isles, G. Kelsey, AC Ferguson-Smith and Erice Imprinting Group: Genomic Imprinting and Physiological Processes in Mammals . In: Cell . tape 176 , no. 5 , p. 952–965 , doi : 10.1016 / j.cell.2019.01.043 (English).
  6. ↑ MB Renfree, S. Suzuki, T. Kaneko-Ishino: The origin and evolution of genomic imprinting and viviparity in mammals. In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. Volume 368, Number 1609, January 2013, pp. 20120151, ISSN  1471-2970 . doi : 10.1098 / rstb.2012.0151 . PMID 23166401 . PMC 3539366 (free full text).
  7. ↑ Marilyn B. Renfree, Timothy A. Hore, Geoffrey Shaw, Jennifer A. Marshall Graves, Andrew J. Pask: Evolution of Genomic Imprinting: Insights from Marsupials and Monotremes. In: Annual Review of Genomics and Human Genetics. 10, 2009, p. 241, doi : 10.1146 / annurev-genom-082908-150026 .
  8. ^ H. Jiang, C. Koehler: Evolution, function, and regulation of genomic imprinting in plant seed development. In: Journal of experimental botany. Volume 63, Number 13, August 2012, pp. 4713-4722, ISSN  1460-2431 . doi : 10.1093 / jxb / ers145 . PMID 22922638 .
  9. ^ C. Gregg: Known unknowns for allele-specific expression and genomic imprinting effects. In: F1000prime reports. Volume 6, 2014, p. 75, ISSN  2051-7599 . doi : 10.12703 / P6-75 . PMID 25343032 . PMC 4166941 (free full text).