Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. As of 2014, there are about 150 imprinted genes known in the mouse and about half that in humans.
Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. It is an epigenetic process that involves DNA methylation and histone methylation without altering the genetic sequence. These epigenetic marks are established ("imprinted") in the germline (sperm or egg cells) of the parents and are maintained through mitotic cell divisions in the somatic cells of an organism.
- 1 Overview
- 2 Imprinted genes in mammals
- 3 Disorders associated with imprinting
- 4 Imprinted genes in other animals
- 5 Imprinted genes in plants
- 6 See also
- 7 References
- 8 External links
In diploid organisms (like humans), the somatic cells possess two copies of the genome, one inherited from the father and one from the mother. Each autosomal gene is therefore represented by two copies, or alleles, with one copy inherited from each parent at fertilization. For the vast majority of autosomal genes, expression occurs from both alleles simultaneously. In mammals, however, a small proportion (<1%) of genes are imprinted, meaning that gene expression occurs from only one allele  (some recent studies have questioned this assertion, claiming that the number of regions of parent-of-origin methylation in, for example, the human genome, is much larger than previously thought). 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.
The term "imprinting" was first used to describe events in the insect Pseudococcus nipae. In Pseudococcids (mealybugs) (Hemiptera, Coccoidea) both the male and female develop from a fertilised egg. In females, all chromosomes remain euchromatic and functional. 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.
Imprinted genes in mammals
That imprinting might be a feature of mammalian development was suggested in breeding experiments in mice carrying reciprocal chromosomal translocations. Nucleus transplantation experiments in mouse zygotes in the early 1980s confirmed that normal development requires the contribution of both the maternal and paternal genomes. The vast majority of mouse embryos derived from parthenogenesis (called parthenogenones, with two maternal or egg genomes) and androgenesis (called 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 (in a 1984 paper).
No naturally occurring cases of parthenogenesis exist in mammals because of imprinted genes. However, in 2004, experimental manipulation by Japanese researchers of a paternal methylation imprint controlling the Igf2 gene led to the birth of a mouse (named Kaguya) with two maternal sets of chromosomes, though it is not a true parthenogenone since cells from two different female mice were used. The researchers were able to succeed by using one egg from an immature parent, thus reducing maternal imprinting, and modifying it to express the gene Igf2, which is normally only expressed by the paternal copy of the gene.
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. Hybrid offspring of two species may exhibit unusual growth due to the novel combination of imprinted genes.
Various methods have been used to identify imprinted genes. In swine, Bischoff et al. 2009 compared transcriptional profiles using short-oligonucleotide microarrays to survey differentially expressed genes between parthenotes (2 maternal genomes) and control fetuses (1 maternal, 1 paternal genome). An intriguing study surveying the transcriptome of murine brain tissues revealed over 1300 imprinted gene loci (approximately 10-fold more than previously reported) by RNA-sequencing from F1 hybrids resulting from reciprocal crosses. The result however has been challenged by others who claimed that this is an overestimation by an order of magnitude due to flawed statistical analysis.
In domesticated livestock, single-nucleotide polymorphisms in imprinted genes influencing foetal growth and development have been shown to be associated with economically important production traits in cattle, sheep and pigs.
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. The generation of a series of such uniparental disomies, which together span the entire genome, allowed the creation of an imprinting map. 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. Around 80% of imprinted genes are found in clusters such as these, called imprinted domains, suggesting a level of co-ordinated control. More recently, genome-wide screens to identify imprinted genes have used differential expression of mRNAs from control fetuses and parthenogenetic or androgenetic fetuses hybridized to expression arrays, allele-specific gene expression using SNP genotyping arrays, transcriptome sequencing, and in silico prediction pipelines.
Imprinting is a dynamic process. It must be possible to erase and re-establish imprints through each generation so that genes that are imprinted in an adult may still be expressed in that adult's offspring. (For example, the maternal genes that control insulin production will be imprinted in a male but will be expressed in any of the male's offspring that inherit these genes.) The nature of imprinting must therefore be epigenetic rather than DNA sequence dependent. In germline cells the imprint is erased and then re-established according to the sex of the individual, i.e. in the developing sperm (during spermatogenesis), a paternal imprint is established, whereas in developing oocytes (oogenesis), a maternal imprint is established. This process of erasure and reprogramming is necessary such that the germ cell imprinting status is relevant to the sex of the individual. In both plants and mammals there are two major mechanisms that are involved in establishing the imprint; these are DNA methylation and histone modifications.
Recently, a new study has suggested a novel inheritable imprinting mechanism in humans that would be specific of placental tissue and that is independent of DNA methylation (the main and classical mechanism for genomic imprinting). Among the hypothetical explanations for this exclusively human phenomenon, two possible mechanisms have been proposed: either a histone modification that confers imprinting at novel placental-specific imprinted loci or, alternatively, a recruitment of DNMTs to these loci by a specific and unknown transcription factor that would be expressed during early trophoblast differentiation.
The grouping of imprinted genes within clusters allows them to share common regulatory elements, such as non-coding RNAs and differentially methylated regions (DMRs). 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. 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 therian mammals (placental mammals and marsupials) and flowering plants. Imprinting of whole chromosomes has been reported in mealybugs (Genus: Pseudococcus). and a fungus gnat (Sciara). It has also been established that X-chromosome inactivation occurs in an imprinted manner in the extra-embryonic tissues of mice and all tissues in marsupials, where it is always the paternal X-chromosome which is silenced.
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. Other imprinted genes are involved in post-natal development, with roles affecting suckling and metabolism.
Hypotheses on the origins of imprinting
A widely accepted hypothesis for the evolution of genomic imprinting is the "parental conflict hypothesis". Also known as the kinship theory of genomic imprinting, 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. The father's genes that encode for imprinting gain greater fitness through the success of the offspring, at the expense of the mother. The mother's evolutionary imperative is often 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. In support of this hypothesis, genomic imprinting has been found in all placental mammals, where post-fertilisation offspring resource consumption at the expense of the mother is high; although it has also been found in oviparous birds where there is relatively little post-fertilisation resource transfer and therefore less parental conflict.
However, our understanding of the molecular mechanisms behind genomic imprinting show that it is the maternal genome that controls much of the imprinting of both its own and the paternally-derived genes in the zygote, making it difficult to explain why the maternal genes would willingly relinquish their dominance to that of the paternally-derived genes in light of the conflict hypothesis.
Another hypothesis proposed is that some imprinted genes act coadaptively to improve both fetal development and maternal provisioning for nutrition and care. In it a subset of paternally expressed genes are co-expressed in both the placenta and the mother's hypothalamus. This would come about through selective pressure from parent-infant coadaptation to improve infant survival. Paternally expressed 3 (Peg3) is a gene for which this hypothesis may apply.
Others have approached their study of the origins of genomic imprinting from a different side, arguing that natural selection is operating on the role of epigenetic marks as machinery for homologous chromosome recognition during meiosis, rather than on their role in differential expression. This argument centers on the existence of epigenetic effects on chromosomes that do not directly affect gene expression, but do depend on which parent the chromosome originated from. This group of epigenetic changes that depend on the chromosome's parent of origin (including both those that affect gene expression and those that do not) are called parental origin effects, and include phenomena such as paternal X inactivation in the marsupials, nonrandom parental chromatid distribution in the ferns, and even mating type switching in yeast. This diversity in organisms that show parental origin effects has prompted theorists to place the evolutionary origin of genomic imprinting before the last common ancestor of plants and animals, over a billion years ago.
Natural selection for genomic imprinting requires genetic variation in a population. A hypothesis for the origin of this genetic variation states that the host-defense system responsible for silencing foreign DNA elements, such as genes of viral origin, mistakenly silenced genes whose silencing turned out to be beneficial for the organism. 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. It has also been postulated that if the retrotransposed gene is inserted close to another imprinted gene, it may just acquire this imprint.
Disorders associated with imprinting
Imprinting may cause problems in cloning, with clones having DNA that is not methylated in the correct positions. 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. 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. 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.
The first imprinted genetic disorders to be described in humans were the reciprocally inherited Prader-Willi syndrome and Angelman syndrome. Both syndromes are associated with loss of the chromosomal region 15q11-13 (band 11 of the long arm of chromosome 15). This region contains the paternally expressed genes SNRPN and NDN and the maternally expressed gene UBE3A.
- Paternal inheritance of a deletion of this region is associated with Prader-Willi syndrome (characterised by hypotonia, obesity, and hypogonadism).
- Maternal inheritance of the same deletion is associated with Angelman syndrome (characterised by epilepsy, tremors, and a perpetually smiling facial expression).
DIRAS3 (NOEY2 or ARH1)
DIRAS3 is a paternally expressed and maternally imprinted gene located on chromosome 1 in humans. Reduced DIRAS3 expression is linked to an increased risk of ovarian and breast cancers; in 41% of breast and ovarian cancers the protein encoded by DIRAS3 is not expressed, suggesting that it functions as a tumor suppressor gene Therefore, if uniparental disomy occurs and 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.
Imprinted genes in other animals
In insects, imprinting affects entire chromosomes. In some insects the entire paternal genome is silenced in male offspring, and thus is involved in sex determination. The imprinting produces effects similar to the mechanisms in other insects that eliminate paternally inherited chromosomes in male offspring, including arrhenotoky.
In placental species, parent-offspring conflict can result in the evolution of strategies, such as genomic imprinting, for embryos to subvert maternal nutrient provisioning. Despite several attempts to find it, genomic imprinting has not been found in the platypus, reptiles, birds or fish. The absence of genomic imprinting in a placental reptile, the southern grass skink, is interesting as genomic imprinting was thought to be associated with the evolution of viviparity and placental nutrient transport.
Studies in domestic livestock, such as dairy and beef cattle, have implicated imprinted genes (e.g. IGF2) in a range of economic traits, including dairy performance in Holstein-Friesian cattle.
Imprinted genes in plants
A similar imprinting phenomenon has also been described in flowering plants (angiosperms). During fertilisation of the egg cell, a second, separate fertilization event gives rise to the endosperm, an extraembryonic structure that nourishes the embryo in a manner analogous to the mammalian placenta. Unlike the embryo, the endosperm is often formed from the fusion of two maternal cells with a male gamete. This results in a triploid genome. The 2:1 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. It has been suggested that these imprinted genes are responsible for the triploid block effect in flowering plants that prevents hybridization between diploids and autotetraploids.
- Ferguson-Smith AC (July 2011). "Genomic imprinting: the emergence of an epigenetic paradigm". Nature Reviews Genetics. 12 (8): 565–75. doi:10.1038/nrg3032. PMID 21765458.
- Bartolomei MS (September 2009). "Genomic imprinting: employing and avoiding epigenetic processes". Genes & Development. 23 (18): 2124–33. doi:10.1101/gad.1841409. PMC 2751984. PMID 19759261.
- Patten MM, Ross L, Curley JP, Queller DC, Bonduriansky R, Wolf JB (August 2014). "The evolution of genomic imprinting: theories, predictions and empirical tests". Heredity. 113 (2): 119–28. doi:10.1038/hdy.2014.29. PMC 4105453. PMID 24755983.
- Reik W, Walter J (January 2001). "Genomic imprinting: parental influence on the genome". Nature Reviews Genetics. 2 (1): 21–32. doi:10.1038/35047554. PMID 11253064.
- Martienssen RA, Colot V (August 2001). "DNA methylation and epigenetic inheritance in plants and filamentous fungi". Science. 293 (5532): 1070–4. doi:10.1126/science.293.5532.1070. PMID 11498574.
- Feil R, Berger F (April 2007). "Convergent evolution of genomic imprinting in plants and mammals". Trends in Genetics. 23 (4): 192–9. doi:10.1016/j.tig.2007.02.004. PMID 17316885.
- Peters J (August 2014). "The role of genomic imprinting in biology and disease: an expanding view". Nature Reviews Genetics. 15 (8): 517–30. doi:10.1038/nrg3766. PMID 24958438.
- Wood AJ, Oakey RJ (November 2006). "Genomic imprinting in mammals: emerging themes and established theories". PLoS Genetics. 2 (11): e147. doi:10.1371/journal.pgen.0020147. PMC 1657038. PMID 17121465.
- Wilkinson LS, Davies W, Isles AR (November 2007). "Genomic imprinting effects on brain development and function". Nature Reviews. Neuroscience. 8 (11): 832–43. doi:10.1038/nrn2235. PMID 17925812.
- Court F, Tayama C, Romanelli V, Martin-Trujillo A, Iglesias-Platas I, Okamura K, Sugahara N, Simón C, Moore H, Harness JV, Keirstead H, Sanchez-Mut JV, Kaneki E, Lapunzina P, Soejima H, Wake N, Esteller M, Ogata T, Hata K, Nakabayashi K, Monk D (April 2014). "Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment". Genome Research. 24 (4): 554–69. doi:10.1101/gr.164913.113. PMC 3975056. PMID 24402520.
- Schrader, Franz (1921). "The chromosomes in Pseudococcus nipæ". Biological Bulletin. 40 (5): 259–270. doi:10.2307/1536736. JSTOR 1536736. Retrieved 2008-07-01.
- Brown SW, Nur U (July 1964). "HETEROCHROMATIC CHROMOSOMES IN THE COCCIDS". Science. 145 (3628): 130–6. Bibcode:1964Sci...145..130B. doi:10.1126/science.145.3628.130. PMID 14171547.
- Hughes-Schrader S (1948). Cytology of coccids (Coccoïdea-Homoptera). Advances in Genetics. 35. pp. 127–203. doi:10.1016/S0065-2660(08)60468-X. ISBN 9780120176021. PMID 18103373.
- Nur U (1990). "Heterochromatization and euchromatization of whole genomes in scale insects (Coccoidea: Homoptera)". Development: 29–34. PMID 2090427.
- Lyon MF, Glenister PH (February 1977). "Factors affecting the observed number of young resulting from adjacent-2 disjunction in mice carrying a translocation". Genetical Research. 29 (1): 83–92. doi:10.1017/S0016672300017134. PMID 559611.
- Barton SC, Surani MA, Norris ML (1984). "Role of paternal and maternal genomes in mouse development". Nature. 311 (5984): 374–6. Bibcode:1984Natur.311..374B. doi:10.1038/311374a0. PMID 6482961.
- Mann JR, Lovell-Badge RH (1984). "Inviability of parthenogenones is determined by pronuclei, not egg cytoplasm". Nature. 310 (5972): 66–7. Bibcode:1984Natur.310...66M. doi:10.1038/310066a0. PMID 6738704.
- McGrath J, Solter D (May 1984). "Completion of mouse embryogenesis requires both the maternal and paternal genomes". Cell. 37 (1): 179–83. doi:10.1016/0092-8674(84)90313-1. PMID 6722870.
- Isles AR, Holland AJ (January 2005). "Imprinted genes and mother-offspring interactions". Early Human Development. 81 (1): 73–7. doi:10.1016/j.earlhumdev.2004.10.006. PMID 15707717.
- Morison IM, Ramsay JP, Spencer HG (August 2005). "A census of mammalian imprinting". Trends in Genetics. 21 (8): 457–65. doi:10.1016/j.tig.2005.06.008. PMID 15990197.
- Reik W, Lewis A (May 2005). "Co-evolution of X-chromosome inactivation and imprinting in mammals". Nature Reviews Genetics. 6 (5): 403–10. doi:10.1038/nrg1602. PMID 15818385.
- "Gene Tug-of-War Leads to Distinct Species". Howard Hughes Medical Institute. 2000-04-30. Retrieved 2008-07-02.
- Bischoff SR, Tsai S, Hardison N, Motsinger-Reif AA, Freking BA, Nonneman D, Rohrer G, Piedrahita JA (November 2009). "Characterization of conserved and nonconserved imprinted genes in swine". Biology of Reproduction. 81 (5): 906–20. doi:10.1095/biolreprod.109.078139. PMC 2770020. PMID 19571260.
- Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C (August 2010). "High-resolution analysis of parent-of-origin allelic expression in the mouse brain". Science. 329 (5992): 643–8. Bibcode:2010Sci...329..643G. doi:10.1126/science.1190830. PMC 3005244. PMID 20616232.
- Hayden EC (April 2012). "RNA studies under fire". Nature. 484 (7395): 428. Bibcode:2012Natur.484..428C. doi:10.1038/484428a. PMID 22538578.
- DeVeale B, van der Kooy D, Babak T (2012). "Critical evaluation of imprinted gene expression by RNA-Seq: a new perspective". PLoS Genetics. 8 (3): e1002600. doi:10.1371/journal.pgen.1002600. PMC 3315459. PMID 22479196.
- Magee DA, Spillane C, Berkowicz EW, Sikora KM, MacHugh DE (August 2014). "Imprinted loci in domestic livestock species as epigenomic targets for artificial selection of complex traits". Animal Genetics. 45 Suppl 1: 25–39. doi:10.1111/age.12168. PMID 24990393.
- Magee DA, Sikora KM, Berkowicz EW, Berry DP, Howard DJ, Mullen MP, Evans RD, Spillane C, MacHugh DE (October 2010). "DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle". BMC Genetics. 11: 93. doi:10.1186/1471-2156-11-93. PMC 2965127. PMID 20942903.
- Cattanach BM, Kirk M (1985). "Differential activity of maternally and paternally derived chromosome regions in mice". Nature. 315 (6019): 496–8. Bibcode:1985Natur.315..496C. doi:10.1038/315496a0. PMID 4000278.
- McLaughlin KJ, Szabó P, Haegel H, Mann JR (January 1996). "Mouse embryos with paternal duplication of an imprinted chromosome 7 region die at midgestation and lack placental spongiotrophoblast". Development. 122 (1): 265–70. PMID 8565838.
- Beechey C, Cattanach BM, lake A, Peters J (2008). "Mouse Imprinting Data and References". MRC Harwell. Retrieved 2008-07-02.
- Bartolomei MS, Tilghman SM (1997). "Genomic imprinting in mammals". Annual Review of Genetics. 31: 493–525. doi:10.1146/annurev.genet.31.1.493. PMC 3941233. PMID 9442905.
- Reik W, Walter J (January 2001). "Genomic imprinting: parental influence on the genome". Nature Reviews Genetics. 2 (1): 21–32. doi:10.1038/35047554. PMID 11253064.
- Kobayashi H, Yamada K, Morita S, Hiura H, Fukuda A, Kagami M, Ogata T, Hata K, Sotomaru Y, Kono T (May 2009). "Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2". Genomics. 93 (5): 461–72. doi:10.1016/j.ygeno.2008.12.012. PMID 19200453.
- Bjornsson HT, Albert TJ, Ladd-Acosta CM, Green RD, Rongione MA, Middle CM, Irizarry RA, Broman KW, Feinberg AP (May 2008). "SNP-specific array-based allele-specific expression analysis". Genome Research. 18 (5): 771–9. doi:10.1101/gr.073254.107. PMC 2336807. PMID 18369178.
- Babak T, Deveale B, Armour C, Raymond C, Cleary MA, van der Kooy D, Johnson JM, Lim LP (November 2008). "Global survey of genomic imprinting by transcriptome sequencing". Current Biology. 18 (22): 1735–41. doi:10.1016/j.cub.2008.09.044. PMID 19026546.
- Luedi PP, Dietrich FS, Weidman JR, Bosko JM, Jirtle RL, Hartemink AJ (December 2007). "Computational and experimental identification of novel human imprinted genes". Genome Research. 17 (12): 1723–30. doi:10.1101/gr.6584707. PMC 2099581. PMID 18055845.
- Reik W, Dean W, Walter J (August 2001). "Epigenetic reprogramming in mammalian development". Science. 293 (5532): 1089–93. doi:10.1126/science.1063443. PMID 11498579.
- Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM (May 2006). "Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes". Genes & Development. 20 (10): 1268–82. doi:10.1101/gad.1416906. PMC 1472902. PMID 16702402.
- Jin B, Li Y, Robertson KD (June 2011). "DNA methylation: superior or subordinate in the epigenetic hierarchy?". Genes & Cancer. 2 (6): 607–17. doi:10.1177/1947601910393957. PMC 3174260. PMID 21941617.
- Metz, C. W. (1938). "Chromosome behavior, inheritance and sex determination in Sciara". American Naturalist. 72 (743): 485–520. doi:10.1086/280803. JSTOR 2457532.
- Alleman M, Doctor J (June 2000). "Genomic imprinting in plants: observations and evolutionary implications". Plant Molecular Biology. 43 (2–3): 147–61. doi:10.1023/A:1006419025155. PMID 10999401.
- Tycko B, Morison IM (September 2002). "Physiological functions of imprinted genes". Journal of Cellular Physiology. 192 (3): 245–58. doi:10.1002/jcp.10129. PMID 12124770.
- Constância M, Pickard B, Kelsey G, Reik W (September 1998). "Imprinting mechanisms". Genome Research. 8 (9): 881–900. doi:10.1101/gr.8.9.881. PMID 9750189.
- Moore T, Haig D (February 1991). "Genomic imprinting in mammalian development: a parental tug-of-war". Trends in Genetics. 7 (2): 45–9. doi:10.1016/0168-9525(91)90230-N. PMID 2035190.
- Haig D (November 1997). "Parental antagonism, relatedness asymmetries, and genomic imprinting". Proceedings of the Royal Society of London B: Biological Sciences. 264 (1388): 1657–62. doi:10.1098/rspb.1997.0230. PMC 1688715. PMID 9404029.
- Haig, D. (2000). "The kinship theory of genomic imprinting". Annual Review of Ecology and Systematics. 31: 9–32. doi:10.1146/annurev.ecolsys.31.1.9.
- McElroy JP, Kim JJ, Harry DE, Brown SR, Dekkers JC, Lamont SJ (April 2006). "Identification of trait loci affecting white meat percentage and other growth and carcass traits in commercial broiler chickens". Poultry Science. 85 (4): 593–605. doi:10.1093/ps/85.4.593. PMID 16615342.
- Tuiskula-Haavisto M, Vilkki J (2007). "Parent-of-origin specific QTL--a possibility towards understanding reciprocal effects in chicken and the origin of imprinting". Cytogenetic and Genome Research. 117 (1–4): 305–12. doi:10.1159/000103192. PMID 17675872.
- Keverne EB, Curley JP (June 2008). "Epigenetics, brain evolution and behaviour" (PDF). Frontiers in Neuroendocrinology. 29 (3): 398–412. doi:10.1016/j.yfrne.2008.03.001. PMID 18439660.
- Wolf JB (May 2009). "Cytonuclear interactions can favor the evolution of genomic imprinting". Evolution; International Journal of Organic Evolution. 63 (5): 1364–71. doi:10.1111/j.1558-5646.2009.00632.x. PMID 19425202.
- Pardo-Manuel de Villena F, de la Casa-Esperón E, Sapienza C (December 2000). "Natural selection and the function of genome imprinting: beyond the silenced minority". Trends in Genetics. 16 (12): 573–9. doi:10.1016/S0168-9525(00)02134-X. PMID 11102708.
- de la Casa-Esperón E, Sapienza C (2003). "Natural selection and the evolution of genome imprinting". Annual Review of Genetics. 37: 349–70. doi:10.1146/annurev.genet.37.110801.143741. PMID 14616065.
- Barlow DP (April 1993). "Methylation and imprinting: from host defense to gene regulation?". Science. 260 (5106): 309–10. Bibcode:1993Sci...260..309B. doi:10.1126/science.8469984. PMID 8469984.
- Chai JH, Locke DP, Ohta T, Greally JM, Nicholls RD (November 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 (11): 813–21. doi:10.1007/s00335-001-2083-1. PMID 11845283.
- Winstead, Edward R. (2001-05-07). "The Legacy of Solid Gold". Genome News Network.
- Lazaraviciute G, Kauser M, Bhattacharya S, Haggarty P, Bhattacharya S (2014). "A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously". Human Reproduction Update. 20 (6): 840–52. doi:10.1093/humupd/dmu033. PMID 24961233.
- Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo WL, Gray JW, Siciliano M, Mills GB, Bast RC (January 1999). "NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas". Proceedings of the National Academy of Sciences of the United States of America. 96 (1): 214–9. Bibcode:1999PNAS...96..214Y. doi:10.1073/pnas.96.1.214. PMC 15119. PMID 9874798.
- Allis CD, Jenuwein T, Reinberg D (2007). Epigenetics. CSHL Press. p. 440. ISBN 978-0-87969-724-2. Retrieved 10 November 2010.
- Scharfmann R (2007). Development of the Pancreas and Neonatal Diabetes. Karger Publishers. pp. 113–. ISBN 978-3-8055-8385-5. Retrieved 10 November 2010.
- Herrick G, Seger J (1999). "Imprinting and Paternal Genome Elimination in Insects". In Ohlsson R. Genomic Imprinting. Results and Problems in Cell Differentiation. 25. Springer Berlin Heidelberg. pp. 41–71. doi:10.1007/978-3-540-69111-2_3. ISBN 978-3-662-21956-0.
- Griffith OW, Brandley MC, Belov K, Thompson MB (March 2016). "Allelic expression of mammalian imprinted genes in a matrotrophic lizard, Pseudemoia entrecasteauxii". Development Genes and Evolution. 226 (2): 79–85. doi:10.1007/s00427-016-0531-x. PMID 26943808.
- Magee DA, Berry DP, Berkowicz EW, Sikora KM, Howard DJ, Mullen MP, Evans RD, Spillane C, MacHugh DE (January 2011). "Single nucleotide polymorphisms within the bovine DLK1-DIO3 imprinted domain are associated with economically important production traits in cattle". The Journal of Heredity. 102 (1): 94–101. doi:10.1093/jhered/esq097. PMID 20817761.
- Sikora KM, Magee DA, Berkowicz EW, Berry DP, Howard DJ, Mullen MP, Evans RD, Machugh DE, Spillane C (January 2011). "DNA sequence polymorphisms within the bovine guanine nucleotide-binding protein Gs subunit alpha (Gsα)-encoding (GNAS) genomic imprinting domain are associated with performance traits". BMC Genetics. 12: 4. doi:10.1186/1471-2156-12-4. PMC 3025900. PMID 21214909.
- Berkowicz EW, Magee DA, Sikora KM, Berry DP, Howard DJ, Mullen MP, Evans RD, Spillane C, MacHugh DE (February 2011). "Single nucleotide polymorphisms at the imprinted bovine insulin-like growth factor 2 (IGF2) locus are associated with dairy performance in Irish Holstein-Friesian cattle". The Journal of Dairy Research. 78 (1): 1–8. doi:10.1017/S0022029910000567. hdl:11019/377. PMID 20822563.
- Garnier O, Laoueillé-Duprat S, Spillane C (2008). "Genomic imprinting in plants". Epigenetics. 3 (1): 14–20. doi:10.4161/epi.3.1.5554. PMID 18259119.
- Nowack MK, Shirzadi R, Dissmeyer N, Dolf A, Endl E, Grini PE, Schnittger A (May 2007). "Bypassing genomic imprinting allows seed development". Nature. 447 (7142): 312–5. Bibcode:2007Natur.447..312N. doi:10.1038/nature05770. hdl:11858/00-001M-0000-0012-3877-6. PMID 17468744.
- Köhler C, Mittelsten Scheid O, Erilova A (March 2010). "The impact of the triploid block on the origin and evolution of polyploid plants". Trends in Genetics. 26 (3): 142–8. doi:10.1016/j.tig.2009.12.006. PMID 20089326.