Genomic imprinting is a genetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such A parent is a Father or Mother; one who sires or gives It is an inheritance process independent of the classical Mendelian inheritance. Mendelian inheritance (or Mendelian genetics or Mendelism) is a set of primary tenets relating to the transmission of hereditary characteristics from parent Imprinted genes are either expressed only from the allele inherited from the mother (eg. H19 or CDKN1C), or in other instances from the allele inherited from the father (eg. H19 is gene for a Non-coding RNA, found in humans and elsewhere Cyclin-dependent kinase inhibitor 1C (p57 Kip2, also known as CDKN1C, is an imprinted human Gene. IGF2). Forms of genomic imprinting have been demonstrated in insects, mammals and flowering plants. Insects ( Class Insecta) are a major group of Arthropods and the most diverse group of Animals on the Earth with over a million described Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands Plants are living Organisms belonging to the kingdom Plantae.

Contents 1 Overview 2 Imprinted genes in mammals 2.1 Genetic mapping of imprinted genes 2.2 Imprinting mechanisms 2.3 Regulation 2.4 Functions of imprinted genes 2.5 Theories on the origins of imprinting 2.6 Problems associated with imprinting 3 Examples 3.1 Prader-Willi and Angelman Syndrome 3.2 NOEY2 4 Imprinted genes in plants 5 See also 6 Notes 7 References 7.1 Scientific journals 8 External links

Overview

In diploid organisms somatic cells possess two copies of the genome. "Haplo" redirects here For the fictional character see The Death Gate Cycle. Somatic cells are any cells forming the body of an organism as opposed to Germline cells In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby Each autosomal gene is therefore represented by two copies, or alleles, with one copy inherited from each parent at fertilisation. An autosome is a non-sex Chromosome. It is an ordinarily paired type of chromosome that is the same in both Sexes of a species. For soil improvement see Fertilization (soil. For the vast majority of autosomal genes, expression occurs from both alleles simultaneously. An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms In mammals however, a small proportion (<1%) of genes are imprinted, meaning that gene expression occurs from only one allele (Wilkinson et al. , 2007). The expressed allele is dependent upon its parental origin. For example, the gene encoding Insulin-like growth factor 2 (IGF2/Igf2) is only expressed from the allele inherited from the father (DeChiara et al. Insulin-like growth factor 2 ( IGF-2) is one of three protein Hormones that share structural similarity to Insulin. , 1991).

The phrase "imprinting" was first used to described events in the insect Pseudococcus nipae (Schrader 1921). In Pseudococcids or mealybugs (Homoptera, Coccoidea) both the male and female develop from a fertilised egg. Mealybug is the common name of insects in Pseudococcidae, a family of unarmored Scale insects found in moist warm climates In females, all chromosomes remain euchromatic and functional. Euchromatin is a lightly packed form of Chromatin that is rich in Gene concentration and is often (but not always under active transcription. In embryos destined to become males, one haploid set of chromosomes becomes heterochromatinised after the sixth cleavage division and remains so in most tissues; males are thus functionally haploid (Brown and Nur 1964; Hughes-Schrader 1948; Nur 1990). "Haplo" redirects here For the fictional character see The Death Gate Cycle. Heterochromatin is a tightly packed form of DNA Its major characteristic is that transcription is limited In insects, imprinting describes the silencing of the paternal genome in males, and thus is involved in sex determination. In mammals, genomic imprinting describes the processes involved in introducing functional inequality between two parental alleles of a gene (Feil and Berger, 2007).

Imprinted genes in mammals

That imprinting might be a feature of mammalian development was suggested in breeding experiments in mice carrying reciprocal translocations (Lyon and Glenister, 1977). Nucleus transplantation experiments in mouse zygotes in the early 1980s confirmed that normal development requires the contribution of both the maternal and paternal genomes. A mouse (plural mice) is a small Animal that belongs to one The vast majority of mouse parthenogenones/gynogenones (with two maternal or egg genomes) and androgenones (with two paternal or sperm genomes) die at, or before, the blastocyst/implantation stage. In the rare instances that they develop to postimplantation stages, gynogenetic embryos show better embryonic development relative to placental development, while for androgenones, the reverse is true. Nevertheless, for the latter, only a few have been described (Barton et al. , 1984; Mann and Lovell-Badge, 1984; McGrath and Solter, 1984).

Parthenogenetic/gynogenetic embryos have twice the normal expression level of maternally derived genes, and lack expression of paternally expressed genes, while the reverse is true for androgenetic embryos. It is now known that there are at least 80 imprinted genes in humans and mice, many of which are involved in embryonic and placental growth and development (Isles and Holland, 2005; Morison et al. , 2005; Reik and Lewis, 2005; Wood and Oakey, 2006).

No naturally occurring cases of parthenogenesis exist in mammals because of imprinted genes. Parthenogenesis (from the Greek παρθένος parthenos, "virgin" + γένεσις genesis, "creation" is an asexual form Experimental manipulation of a paternal methylation imprint controlling the Igf2 gene has, however, recently allowed the creation of rare individual mice with two maternal sets of chromosomes - but this is not a true parthenogenone. Hybrid offspring of two species may exhibit unusual growth due to the novel combination of imprinted genes. In Biology, hybrid has two meanings The first meaning is the result of interbreeding between two animals or plants of different taxa. ^[1]

Genetic mapping of imprinted genes

At the same time as the generation of the gynogenetic and androgenetic embryos discussed above, mouse embryos were also being generated that contained only small regions that were derived from either a paternal or maternal source (Cattanach and Kirk, 1985; McLaughlin et al. , 1996). The generation of a series of such uniparental disomies, which together span the entire genome, allowed the creation of an imprinting map. ^[2] Those regions which when inherited from a single parent result in a discernible phenotype contain imprinted gene(s). Further research showed that within these regions there were often numerous imprinted genes (Bartolomei and Tilghman 1997). Around 80% of imprinted genes are found in clusters such as these, called imprinted domains, suggesting a level of co-ordinated control (Reik and Walter 2001).

Imprinting mechanisms

Imprinting is a dynamic process. It must be possible to erase and re-establish the imprint through each generation. The nature of the imprint must therefore be epigenetic (modifications to the structure of the DNA rather than the sequence). In Biology, the term epigenetics refers to changes in Gene expression caused by mechanisms other than changes in the underlying DNA sequence In germline cells the imprint is erased, and then re-established according to the sex of the individual; i. In Biology and Genetics, the germline of a mature or developing individual is the line (sequence of Germ cells that have genetic material that An organism's sex is defined by the gametes it produces males produce male gametes (spermatozoa or Sperm) while females produce female gametes (ova or Egg cells; individual e. in the developing sperm, a paternal imprint is established, whereas in developing oocytes, a maternal imprint is established. This process of erasure and reprogramming is necessary such that the current imprinting status is relevant to the sex of the individual. Reprogramming refers to erasure and remodeling of epigenetic marks such as DNA methylation, during mammalian development In both plants and mammals there are two major mechanisms that are involved in establishing the imprint; these are DNA methylation and histone modifications. DNA methylation is a type of chemical modification of DNA that can be inherited and subsequently removed without changing the original DNA sequence In Biology, histones are the chief Protein components of Chromatin.

Regulation

The grouping of imprinted genes within clusters allows them to share common regulatory elements, such as non-coding RNAs and differentially methylated regions (DMRs). Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units When these regulatory elements control the imprinting of one or more genes, they are known as imprinting control regions (ICR). The expression of non-coding RNAs, such as Air on mouse chromosome 17 and KCNQ1OT1 on human chromosome 11p15. 5, have been shown to be essential for the imprinting of genes in their corresponding regions.

Differentially methylated regions are generally segments of DNA rich in cytosine and guanine nucleotides, with the cytosine nucleotides methylated on one copy but not on the other. Cytosine is one of the five main bases found in DNA and RNA. It is a Pyrimidine derivative with a Heterocyclic Aromatic ring Guanine is one of the five main Nucleobases found in the Nucleic acids DNA and RNA, the others being Adenine, Cytosine, Contrary to expectation, methylation does not necessarily mean silencing; instead, the effect of methylation depends upon the default state of the region.

Functions of imprinted genes

The control of expression of specific genes by genomic imprinting is unique to placental mammals (eutherians and marsupials) and flowering plants. See also Evolution of mammals Eutheria ("true beast" are a group of Mammals consisting of Placental mammals plus all extinct Mammals Marsupials are an Infraclass of Mammals characterized by a distinctive pouch (called the marsupium) in which females carry their young through Imprinting of whole chromosomes has been reported in mealybugs (Brown and Nur. 1964; Hughes-Schrader. 1948; Schrader 1921; Nur. 1990) and a fungus gnat (Sciara) (Metz. Fungus gnats are small dark short-lived flies, of the families Sciaridae, Diadocidiidae, Ditomyiidae, Keroplatidae, Bolitophilidae 1938). It has also been established that X-chromosome inactivation occurs in an imprinted manner in the extra-embryonic tissues of mice, where it is always the paternal X-chromosome which is silenced (Alleman and Doctor, 2000; Reik and Walter, 2001). The X chromosome is one of the two sex-determining Chromosomes in many animal species including mammals (the other is the Y chromosome)

The majority of imprinted genes in mammals have been found to have roles in the control of embryonic growth and development, including development of the placenta (Isles and Holland 2005; Tycko and Morison 2002). Other imprinted genes are involved in post-natal development, with roles affecting suckling and metabolism (Constancia et al. , 2004; Tycko and Morison, 2002).

Theories on the origins of imprinting

Imprinting appears to be able to increase the evolutionary fitness of genes in two ways, so either or both could be responsible for its origins. Fitness (often denoted w in Population genetics models is a central concept in evolutionary theory.

A widely accepted hypothesis for the occurrence of genomic imprinting is the "parental conflict hypothesis" (Moore and Haig 1991). This hypothesis states that the inequality between parental genomes due to imprinting is a result of the differing interests of each parent in terms of the evolutionary fitness of their genes. Sexual conflict occurs when the two Sexes have conflicting optimal fitness strategies concerning Reproduction, leading to Evolutionary arms race Fitness (often denoted w in Population genetics models is a central concept in evolutionary theory. The father is more 'interested' in the growth of his offspring, at the expense of the mother. The father is defined as the Male Parent of an offspring The Adjective "paternal" refers to father parallel to "maternal" for "Mom" "Mum" and "Mommy" redirect here The mother's interest is to conserve resources for her own survival while providing sufficient nourishment to current and subsequent litters. Accordingly, paternally expressed genes tend to be growth promoting whereas maternally expressed genes tend to be growth limiting (Moore and Haig 1991).

Another hypothesis behind the origins of genomic imprinting is that this phenomenon evolved to silence foreign DNA elements, such as genes of viral origin. There appears to be an over-representation of retrotransposed genes, that is to say genes that are inserted into the genome by viruses, among imprinted genes. Transposons are sequences of DNA that can move around to different positions within the Genome of a single cell, a process called transposition A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable It has also been postulated that if the retrotransposed gene is inserted close to another imprinted gene, it may just acquire this imprint (Chai et. al 2001).

Problems associated with imprinting

Imprinting may cause problems in cloning, with clones having DNA that is not methylated in the correct position. Cloning in Biology is the process of producing populations of genetically-identical individuals that occurs in nature when organisms such as Bacteria, Insects Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. It is possible that this is due to a lack of time for reprogramming to be completely achieved. When a nucleus is added to an egg during somatic cell nuclear transfer, the egg starts dividing in minutes, as compared to the days or months it takes for reprogramming during embryonic development. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed Genetics and Developmental biology, somatic cell nuclear transfer ( SCNT) is a Laboratory technique for creating an Ovum with a donor An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular If time is the responsible factor, it may be possible to delay cell division in clones, giving time for proper reprogramming to occur.

An allele of the "callipyge" (from the Greek for "beautiful buttocks"), or CLPG, gene in sheep produces large buttocks consisting of muscle with very little fat. Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly The large-buttocked phenotype only occurs when the allele is present on the copy of chromosome 18 inherited from a sheep's father and is not on the copy of chromosome 18 inherited from that sheep's mother. ^[3]

Examples

Prader-Willi and Angelman Syndrome

Several genetic diseases that map to 15q11 (band 11 of the long arm of chromosome 15) in humans are due to abnormal imprinting. A genetic disorder is a condition caused by abnormalities in Genes or Chromosomes While some diseases such as Cancer, are due to genetic abnormalities acquired This region is differently imprinted in maternal and paternal chromosomes, and both imprintings are needed for normal development. In a normal individual, the maternal allele is methylated, while the paternal allele is unmethylated. It is possible for an individual to fail to inherit a properly imprinted 15q11 from one parent, as a result either of deletion of the 15q11 region from that parent's chromosome 15 or, less frequently, of uniparental disomy (in which both copies have been taken from the other parent's genes). Uniparental disomy ( UPD) occurs when a person receives two copies of a Chromosome, or part of a chromosome from one parent and no copies from the other parent

• If neither copy of 15q11 has paternal imprinting, the result is Prader-Willi syndrome (characterised by hypotonia, obesity, and hypogonadism). Prader-Willi syndrome (abbreviated PWS) is a very rare Genetic disorder, in which seven genes (or some subset thereof on chromosome 15 are missing or unexpressed Hypotonia is a condition of abnormally low Muscle tone (the amount of tension or resistance to movement in a muscle often involving reduced muscle strength Obesity is a condition in which excess Body fat has accumulated to such an extent that health may be negatively affected Hypogonadism is a medical term for a defect of the Reproductive system that results in lack of function of the Gonads ( ovaries or testes)
• If neither copy has maternal imprinting, the result is Angelman syndrome (characterised by epilepsy, tremors, and a perpetually smiling facial expression). Angelman syndrome (AS is a neuro- Genetic disorder characterized by intellectual and Developmental delay, sleep disturbance Seizures, jerky movements Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. Tremor is an unintentional somewhat rhythmic muscle movement involving to-and-from movements (oscillations of one or more parts of the body This article is about the facial expression For the typographical symbol see Smiley. A facial expression results from one or more motions or positions of the Muscles of the Face.

NOEY2

NOEY2 is a paternally expressed imprinted gene located on chromosome 1 in humans. NOEY2 is a gene located on Chromosome 1 in humans It is paternally imprinted, and is linked to Breast cancer. Loss of NOEY2 expression is linked to an increased risk of ovarian and breast cancers; in 41% of breast and ovarian cancers the protein transcribed by NOEY2 is not expressed, suggesting that it functions as a tumour suppressor^[4] Therefore, if a person inherits both chromosomes from the mother, the gene will not be expressed and the individual is put at a greater risk for breast and ovarian cancer. A tumor suppressor gene, or antioncogene is a Gene that protects a cell from one step on the path to cancer

Imprinted genes in plants

Decades after imprinting was demonstrated in the mouse, a similar phenomena was observed in flowering plants (angiosperms). The flowering plants or angiosperms ( Angiospermae or Magnoliophyta) are the most widespread group During fertilisation of the embryo in flowers, a second separate fertilisation event gives rise to the endosperm, an extraembryonic structure that nourishes the seed similar to the mammalian placenta. Endosperm is the tissue produced in the Seeds of most Flowering plants around the time of fertilization A seed (in some plants referred to as a kernel) is a small embryonic Plant enclosed in a covering called the seed coat usually with some stored The placenta is an Ephemeral organ present in placental Vertebrates, such as Eutherial Mammals and Sharks during Gestation Unlike the embryo, the endosperm often contains two copies of the maternal genome and fusion with a male gamete results in a triploid genome. This uneven ratio of maternal to paternal genomes appears to be critical for seed development. Some genes are found to be expressed from both maternal genomes while others are expressed exclusively from the lone paternal copy (Nowack et al. , 2007).

See also

• Metabolic imprinting
• Bookmarking
• Epigenetics

Notes

1. ^ HHMI News: Gene Tug-of-War Leads to Distinct Species
2. ^ Untitled Document
3. ^ "The Legacy of Solid Gold", Genome News Network, May 7, 2001. Metabolic imprinting refers to the Epigenetic programming of Metabolism during the pre-natal and neo-natal periods In Genetics and Epigenetics, bookmarking is a biological phenomenon believed to function as an epigenetic mechanism for transmitting Cellular memory of In Biology, the term epigenetics refers to changes in Gene expression caused by mechanisms other than changes in the underlying DNA sequence  
4. ^ "NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas", The National Academy of Sciences, January 5, 1999.  

References

Scientific journals

• Bartolomei, M. S. and Tilghman, S. M. (1997). "Genomic imprinting in mammals" (subscription required). Annu Rev Genet 31: 493-525. This is the article on the publisher Annual Reviews whose titles are invariably called Annual review of. doi:10.1146/annurev.genet.31.1.493. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
• Barton, S. C. ; et al (1984). "Role of paternal and maternal genomes in mouse development". Nature 311 (5984): 374-376. Nature is a prominent Scientific journal, first published on 4 November 1869 doi:10.1038/311374a0. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 6482961.  
• Brown S. W. and Nur U. (1964). "Heterochromatic chromosomes in the coccids". Science 145: 130-136. Science is the Academic journal of the American Association for the Advancement of Science and is considered one of the world's most prestigious Scientific doi:10.1126/science.145.3628.130. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14171547.  
• Cattanach, B. M. and Kirk, M. 1985. Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315(6019), pp. 496-498
• Chai, J. H. et al. 2001. Retrotransposed genes such as Frat3 in the mouse Chromosome 7C Prader-Willi syndrome region acquire the imprinted status of their insertion site. Mammalian Genome 12, 813–821
• Constancia, M. et al. 2004. Resourceful imprinting. Nature 432, pp. 53-57
• DeChiara, T. M. et al. 1991. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, pp. 849-859
• Feil, R and Berger, F 2007. Convergent evolution of genomic imprinting in plants and mammals. Trends in Genetics 23, pp. 192-199
• Hughes-Schrader, S. 1948. Cytology of Coccids (Coccoidea-Homoptera). Advances in Genetics 2, pp127-203.
• Isles, A. R. and Holland, A. J. 2005. Imprinted genes and mother-offspring interactions. Early Human Development 81, pp. 73-77.
• Lyon, M. F. and Glenister, P. H. 1977. Factors affecting the observed numbers of young resulting from adjacent-2 disjunction in mice carrying a translocation. Genetics Research, 29, pp. 83-92.
• Mann, J. R. and Lovell-Badge, R. H. 1984. Inviability of parthenogenones in determined by pronuclei, not egg cytoplasm. Nature 310, pp. 66-67.
• McGrath, J. and Solter, D. 1984. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37(1), pp. 179-183.
• McLaughlin, K. J. et al. 1996. Mouse embryos with paternal duplication of an imprinted chromosome 7 region die at midgestation and lack placental spongiotrophoblast. Development 122, pp. 265-270.
• Metz, C. W. 1938. Chromosome behavior, inheritance and sex determination in Sciara. Am. Nat. 72, pp. 485-520.
• Moore, T. and Haig, D. 1991. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet 7(2), pp. 45-49
• Morison, I. M. et al. 2005. A census of mammalian imprinting. Trends Genet 21(8), pp. 457-465.
• Nowack et al. 2007. Bypassing genomic imprinting allows seed development. Nature 447, pp. 312-316.
• Nur, U. (1990). Heterochromatization and euchromatization of whole genome in scale insects (Coccoidea:Homoptera). Development Suppl. 29-34.
• Reik, W. and Lewis, A. 2005. Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet 6(5), pp. 403-410.
• Reik, W. and Walter, J. 2001. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2(1), pp. 21-32.
• Schrader, F. 1921. The chromosomes of Pseudococcus nipae. Biol Bull. 40, pp 259-270.
• Tycko, B. and Morison, I. M. 2002. Physiological functions of imprinted genes. J Cell Physiol 192(3), pp. 245-258
• Wilkinson, S. L. , Davies, W and Isles A. R. 2007. Genomic imprinting effects on brain development and function. Nature Reviews Neuroscience 8. pp 832-843
• Wood, A. J. and Oakey, R. J. 2006. Genomic Imprinting in Mammals: Emerging Themes and Established Theories. PLoS Genetics 2(11), e147.

External links

• Imprinted Gene and Parent-of-origin Effect Database
• MRC Harwell Imprinting Resource
• geneimprint.com
• J. Kimball's Imprinted Genes Site
• MeSH Genomic+imprinting

Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books

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