Genomic imprinting

Last updated

Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the female or male parent. [1] [2] [3] [4] [5] Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. [6] Forms of genomic imprinting have been demonstrated in fungi, plants and animals. [7] [8] In 2014, there were about 150 imprinted genes known in mice and about half that in humans. [9] As of 2019, 260 imprinted genes have been reported in mice and 228 in humans. [10]

Contents

Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. [11] 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. [12]

Appropriate imprinting of certain genes is important for normal development. Human diseases involving genomic imprinting include Angelman, Prader–Willi, and Beckwith–Wiedemann syndromes. [13] Methylation defects have also been associated with male infertility. [3]

Overview

In diploid organisms (like humans), the somatic cells possess two copies of the genome, one inherited from the male and one from the female. Each autosomal gene is therefore represented by two copies, or alleles, with one copy inherited from each parent at fertilization. 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 male. Although imprinting accounts for a small proportion of mammalian genes, they play an important role in embryogenesis particularly in the formation of visceral structures and the nervous system. [14]

The term "imprinting" was first used to describe events in the insect Pseudococcus nipae . [15] 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. [16] [17] [18]

Imprinted genes in mammals

That imprinting might be a feature of mammalian development was suggested in breeding experiments in mice carrying reciprocal chromosomal translocations. [19] 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). [20] [21] [22] Nevertheless, in 2018 genome editing allowed for bipaternal and viable bimaternal [23] [24] mouse and even (in 2022) parthenogenesis, still this is far from full reimprinting. [25] Finally in March 2023 viable bipaternal embryos were created. [26]

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. [12] [27] [28] [29] Hybrid offspring of two species may exhibit unusual growth due to the novel combination of imprinted genes. [30]

Various methods have been used to identify imprinted genes. In swine, Bischoff et al. compared transcriptional profiles using DNA microarrays to survey differentially expressed genes between parthenotes (2 maternal genomes) and control fetuses (1 maternal, 1 paternal genome). [31] 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. [32] 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. [33] [34]

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. [35] [36]

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. [37] [38] The generation of a series of such uniparental disomies, which together span the entire genome, allowed the creation of an imprinting map. [39] 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. [40] Around 80% of imprinted genes are found in clusters such as these, called imprinted domains, suggesting a level of co-ordinated control. [5] 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 gene expression profiling microarrays, [41] allele-specific gene expression using SNP genotyping microarrays, [42] transcriptome sequencing, [43] and in silico prediction pipelines. [44]

Imprinting mechanisms

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 [45] 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 [46] 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). This was observed in humans, but not in mice, suggesting development after the evolutionary divergence of humans and mice, ~80 Mya. Among the hypothetical explanations for this novel 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.

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). 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 antisense Igf2r RNA (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. [47]

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. [48]

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 ) [15] [16] [17] [18] and a fungus gnat (Sciara). [49] 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. [5] [50]

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. [27] [51] Other imprinted genes are involved in post-natal development, with roles affecting suckling and metabolism. [51] [52]

Hypotheses on the origins of imprinting

A widely accepted hypothesis for the evolution of genomic imprinting is the "parental conflict hypothesis". [53] 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. [54] [55] 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. [53] 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 [56] [57] where there is relatively little post-fertilisation resource transfer and therefore less parental conflict. A small number of imprinted genes are fast evolving under positive Darwinian selection possibly due to antagonistic co-evolution. [58] The majority of imprinted genes display high levels of micro-synteny conservation and have undergone very few duplications in placental mammalian lineages. [58]

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. [59]

Another hypothesis proposed is that some imprinted genes act coadaptively to improve both fetal development and maternal provisioning for nutrition and care. [9] [59] [60] 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. [9]

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. [61] 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. [62] 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. [62] 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. [61]

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. [63] 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. [64]

Imprinted loci phenotypic signatures

Unfortunately, the relationship between the phenotype and genotype of imprinted genes is solely conceptual. The idea is frameworked using two alleles on a single locus and hosts three different possible classes of genotypes. [65] The reciprocal heterozygotes genotype class contributes to understanding how imprinting will impact genotype to phenotype relationship. Reciprocal heterozygotes have a genetically equivalent, but they are phenotypically nonequivalent. [66] Their phenotype may not be dependent on the equivalence of the genotype. This can ultimately increase diversity in genetic classes, expanding flexibility of imprinted genes. [67] This increase will also force a higher degree in testing capabilities and assortment of tests to determine the presences of imprinting.

When a locus is identified as imprinted, two different classes express different alleles. [65] Inherited imprinted genes of offspring are believed to be monoallelic expressions. A single locus will entirely produce one's phenotype although two alleles are inherited. This genotype class is called parental imprinting, as well as dominant imprinting. [68] Phenotypic patterns are variant to possible expressions from paternal and maternal genotypes. Different alleles inherited from different parents will host different phenotypic qualities. One allele will have a larger phenotypic value and the other allele will be silenced. [65] Underdominance of the locus is another possibility of phenotypic expression. Both maternal and paternal phenotypes will have a small value rather than one hosting a large value and silencing the other.

Statistical frameworks and mapping models are used to identify imprinting effects on genes and complex traits. Allelic parent-of-origin influences the vary in phenotype that derive from the imprinting of genotype classes. [65] These models of mapping and identifying imprinting effects include using unordered genotypes to build mapping models. [67] These models will show classic quantitative genetics and the effects of dominance of the imprinted genes.

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.[ citation needed ]

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. [69]

In vitro fertilisation, including ICSI, is associated with an increased risk of imprinting disorders, with an odds ratio of 3.7 (95% confidence interval 1.4 to 9.7). [70]

Male infertility

Epigenetic deregulations at H19 imprinted gene in sperm have been observed associated with male infertility. [71] Indeed, methylation loss at H19 imprinted gene has been observed associated with MTHFR gene promoter hypermethylation in semen samples from infertile males. [71]

Prader-Willi/Angelman

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.

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. [72] 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.

Other

Other conditions involving imprinting include Beckwith-Wiedemann syndrome, Silver-Russell syndrome, and pseudohypoparathyroidism. [73]

Transient neonatal diabetes mellitus can also involve imprinting. [74]

The "imprinted brain hypothesis" argues that unbalanced imprinting may be a cause of autism and psychosis.

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. [75]

In social honey bees, the parent of origin and allele-specific genes has been studied from reciprocal crosses to explore the epigenetic mechanisms underlying aggressive behavior. [76]

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 Pseudemoia entrecasteauxii, is interesting as genomic imprinting was thought to be associated with the evolution of viviparity and placental nutrient transport. [77]

Studies in domestic livestock, such as dairy and beef cattle, have implicated imprinted genes (e.g. IGF2) in a range of economic traits, [78] [79] [35] including dairy performance in Holstein-Friesian cattle. [80]

Mouse foraging behavior

Foraging behavior in mice studied is influenced by a sexually dimorphic allele expression implicating a cross-gender imprinting influence that varies throughout the body and may dominate expression and shape a behavior. [81] [82]

Imprinted genes in plants

A similar imprinting phenomenon has also been described in flowering plants (angiosperms). [83] During fertilization 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. [84] 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. [85] Several computational methods to detect imprinting genes in plants from reciprocal crosses have been proposed. [86] [87] [88]

See also

Related Research Articles

<span class="mw-page-title-main">Epigenetics</span> Study of DNA modifications that do not change its sequence

In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. They can lead to cancer.

<span class="mw-page-title-main">Non-Mendelian inheritance</span> Type of pattern of inheritance

Non-Mendelian inheritance is any pattern in which traits do not segregate in accordance with Mendel's laws. These laws describe the inheritance of traits linked to single genes on chromosomes in the nucleus. In Mendelian inheritance, each parent contributes one of two possible alleles for a trait. If the genotypes of both parents in a genetic cross are known, Mendel's laws can be used to determine the distribution of phenotypes expected for the population of offspring. There are several situations in which the proportions of phenotypes observed in the progeny do not match the predicted values.

<span class="mw-page-title-main">X-inactivation</span> Inactivation of copies of X chromosome

X-inactivation is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a transcriptionally inactive structure called heterochromatin. As nearly all female mammals have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome.

<span class="mw-page-title-main">Agouti-signaling protein</span> Protein-coding gene in the species Homo sapiens

Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte produces phaeomelanin, or eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti, which the gene is named after. In other species such as horses, agouti signalling is responsible for determining which parts of the body will be red or black. Mice with wildtype agouti will be grey-brown, with each hair being partly yellow and partly black. Loss of function mutations in mice and other species cause black fur coloration, while mutations causing expression throughout the whole body in mice cause yellow fur and obesity.

<span class="mw-page-title-main">GABRB3</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid receptor subunit beta-3 is a protein that in humans is encoded by the GABRB3 gene. It is located within the 15q12 region in the human genome and spans 250kb. This gene includes 10 exons within its coding region. Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel. The beta-3 subunit is expressed at different levels within the cerebral cortex, hippocampus, cerebellum, thalamus, olivary body and piriform cortex of the brain at different points of development and maturity. GABRB3 deficiencies are implicated in many human neurodevelopmental disorders and syndromes such as Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. The effects of methaqualone and etomidate are mediated through GABBR3 positive allosteric modulation.

<span class="mw-page-title-main">H19 (gene)</span> Negative regulation (or limiting) of body weight and cell proliferation

H19 is a gene for a long noncoding RNA, found in humans and elsewhere. H19 has a role in the negative regulation of body weight and cell proliferation. This gene also has a role in the formation of some cancers and in the regulation of gene expression.

<span class="mw-page-title-main">KCNQ1OT1</span>

KCNQ1 overlapping transcript 1, also known as KCNQ1OT1, is a long non-coding RNA gene found in the KCNQ1 locus. This locus consists of 8–10 protein-coding genes, specifically expressed from the maternal allele, and the paternally expressed non-coding RNA gene KCNQ1OT1. KCNQ1OT1 and KCNQ1 are imprinted genes and are part of an imprinting control region (ICR). Mitsuya identified that KCNQ1OT1 is an antisense transcript of KCNQ1. KCNQ1OT1 is a paternally expressed allele and KCNQ1 is a maternally expressed allele. KCNQ1OT1 is a nuclear, 91 kb transcript, found in close proximity to the nucleolus in certain cell types.

Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region. These regulators work to enhance or silence the expression of genes. Since these regulators work in opposition to each other, they normally interact with chromatin at different times. However, in bivalent chromatin, both types of regulators are interacting with the same domain at the same time. Bivalent chromatin domains are normally associated with promoters of transcription factor genes that are expressed at low levels. Bivalent domains have also been found to play a role in developmental regulation in pluripotent embryonic stems cells, gene imprinting and cancer.

Skewed X-chromosome inactivation occurs when the X-inactivation of one X chromosome is favored over the other, leading to an uneven number of cells with each chromosome inactivated. It is usually defined as one allele being found on the active X chromosome in over 75% of cells, and extreme skewing is when over 90% of cells have inactivated the same X chromosome. It can be caused by primary nonrandom inactivation, either by chance due to a small cell pool or directed by genes, or by secondary nonrandom inactivation, which occurs by selection.

mir-127

mir-127 microRNA is a short non-coding RNA molecule with interesting overlapping gene structure. miR-127 functions to regulate the expression levels of genes involved in lung development, placental formation and apoptosis. Aberrant expression of miR-127 has been linked to different cancers.

<span class="mw-page-title-main">Transgenerational epigenetic inheritance</span> Epigenetic transmission without DNA primary structure alteration

Transgenerational epigenetic inheritance is the transmission of epigenetic markers and modifications from one generation to multiple subsequent generations without altering the primary structure of DNA. Thus, the regulation of genes via epigenetic mechanisms can be heritable; the amount of transcripts and proteins produced can be altered by inherited epigenetic changes. In order for epigenetic marks to be heritable, however, they must occur in the gametes in animals, but since plants lack a definitive germline and can propagate, epigenetic marks in any tissue can be heritable.

<i>Ube3a-ATS</i> Non-coding RNA in the species Homo sapiens

UBE3A-ATS/Ube3a-ATS (human/mouse), otherwise known as ubiquitin ligase E3A-ATS, is the name for the antisense DNA strand that is transcribed as part of a larger transcript called LNCAT at the Ube3a locus. The Ube3a locus is imprinted and in the central nervous system expressed only from the maternal allele. Silencing of Ube3a on the paternal allele is thought to occur through the Ube3a-ATS part of LNCAT, since non-coding antisense transcripts are often found at imprinted loci. The deletion and/or mutation of Ube3a on the maternal chromosome causes Angelman syndrome (AS) and Ube3a-ATS may prove to be an important aspect in finding a therapy for this disease. While in patients with AS the maternal Ube3a allele is inactive, the paternal allele is intact but epigenetically silenced. If unsilenced, the paternal allele could be a source of active Ube3a protein in AS patients. Therefore, understanding the mechanisms of how Ube3a-ATS might be involved in silencing the paternal Ube3a may lead to new therapies for AS. This possibility has been demonstrated by a recent study where the drug topotecan, administered to mice suffering from AS, activated expression of the paternal Ube3a gene by lowering the transcription of Ube3a-ATS.

Autism spectrum disorder (ASD) refers to a variety of conditions typically identified by challenges with social skills, communication, speech, and repetitive sensory-motor behaviors. The 11th International Classification of Diseases (ICD-11), released in January 2021, characterizes ASD by the associated deficits in the ability to initiate and sustain two-way social communication and restricted or repetitive behavior unusual for the individual's age or situation. Although linked with early childhood, the symptoms can appear later as well. Symptoms can be detected before the age of two and experienced practitioners can give a reliable diagnosis by that age. However, official diagnosis may not occur until much older, even well into adulthood. There is a large degree of variation in how much support a person with ASD needs in day-to-day life. This can be classified by a further diagnosis of ASD level 1, level 2, or level 3. Of these, ASD level 3 describes people requiring very substantial support and who experience more severe symptoms. ASD-related deficits in nonverbal and verbal social skills can result in impediments in personal, family, social, educational, and occupational situations. This disorder tends to have a strong correlation with genetics along with other factors. More research is identifying ways in which epigenetics is linked to autism. Epigenetics generally refers to the ways in which chromatin structure is altered to affect gene expression. Mechanisms such as cytosine regulation and post-translational modifications of histones. Of the 215 genes contributing, to some extent in ASD, 42 have been found to be involved in epigenetic modification of gene expression. Some examples of ASD signs are specific or repeated behaviors, enhanced sensitivity to materials, being upset by changes in routine, appearing to show reduced interest in others, avoiding eye contact and limitations in social situations, as well as verbal communication. When social interaction becomes more important, some whose condition might have been overlooked suffer social and other exclusion and are more likely to have coexisting mental and physical conditions. Long-term problems include difficulties in daily living such as managing schedules, hypersensitivities, initiating and sustaining relationships, and maintaining jobs.

<span class="mw-page-title-main">Tsix</span> Non-coding RNA in the species Homo sapiens

Tsix is a non-coding RNA gene that is antisense to the Xist RNA. Tsix binds Xist during X chromosome inactivation. The name Tsix comes from the reverse of Xist, which stands for X-inactive specific transcript.

<span class="mw-page-title-main">Wolf Reik</span> German molecular biologist

Wolf Reik FRS is a German-British molecular biologist and an honorary group leader at the Babraham Institute, honorary professor of Epigenetics at the University of Cambridge and associate faculty at the Wellcome Trust Sanger Institute. He was announced as the director of Altos Labs Cambridge Institute when the company launched on 19 January 2022.

Epigenetics of human development is the study of how epigenetics effects human development.

<span class="mw-page-title-main">RTL1</span> Protein-coding gene in the species Homo sapiens

RTL1 is a retrotransposon derived protein coding gene. It is also known as PEG11 and is a paternally expressed imprinted gene, part of genomic imprinting. RTL1 plays an important role in the maintenance of fetal capillaries and is expressed in high quantities during late stage of fetal development. The expression of this gene is important for the development of the placenta, the fetus-maternal interface. Because the placenta is the first organ to form during the development of an embryo, problems in its establishment and biological role lead to complications during gestation. This organ maintains the fetus throughout the pregnancy and is therefore sensitive to disruptions. Studies in mice suggest that disruption of the RTL1 concentration, whether increasing or decreasing the amount of this protein coding gene, can lead to serious errors in the conservation of placental fetal capillaries. RTL1 knockout mice have shown obstruction in fetal development along with late fetal/neonatal death. Studies from sheep homologs suggest that high expression levels of RTL1 can lead to skeletal muscle hypertrophy This is due to over-expression patterns in the paternal allele specific gene.

Monoallelic gene expression (MAE) is the phenomenon of the gene expression, when only one of the two gene copies (alleles) is actively expressed (transcribed), while the other is silent. Diploid organisms bear two homologous copies of each chromosome (one from each parent), a gene can be expressed from both chromosomes (biallelic expression) or from only one (monoallelic expression). MAE can be Random monoallelic expression (RME) or Constitutive monoallelic expression (constitutive). Constitutive monoallelic expression occurs from the same specific allele throughout the whole organism or tissue, as a result of genomic imprinting. RME is a broader class of monoallelic expression, which is defined by random allelic choice in somatic cells, so that different cells of the multi-cellular organism express different alleles.

Marisa Bartolomei is an American cell biologist, the Perelman Professor of Cell and Developmental Biology and Co-Director of the Epigenetics Institute at the Perelman School of Medicine at the University of Pennsylvania. Her research considers epigenetic processes including genomic imprinting. She was elected to the National Academy of Sciences in 2021.

X chromosome reactivation (XCR) is the process by which the inactive X chromosome (the Xi) is re-activated in the cells of eutherian female mammals. Therian female mammalian cells have two X chromosomes, while males have only one, requiring X-chromosome inactivation (XCI) for sex-chromosome dosage compensation. In eutherians, XCI is the random inactivation of one of the X chromosomes, silencing its expression. Much of the scientific knowledge currently known about XCR comes from research limited to mouse models or stem cells.

References

  1. ↑ Ferguson-Smith AC (July 2011). "Genomic imprinting: the emergence of an epigenetic paradigm". Nature Reviews. Genetics. 12 (8): 565–575. doi:10.1038/nrg3032. PMID   21765458. S2CID   23630392. Closed Access logo transparent.svg
  2. ↑ Bartolomei MS (September 2009). "Genomic imprinting: employing and avoiding epigenetic processes". Genes & Development. 23 (18): 2124–2133. doi:10.1101/gad.1841409. PMC   2751984 . PMID   19759261.
  3. 1 2 Rotondo JC, Selvatici R, Di Domenico M, Marci R, Vesce F, Tognon M, Martini F (September 2013). "Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males". Epigenetics. 8 (9): 990–997. doi:10.4161/epi.25798. PMC   3883776 . PMID   23975186.
  4. ↑ 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): 119–128. doi:10.1038/hdy.2014.29. PMC   4105453 . PMID   24755983.
  5. 1 2 3 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. S2CID   12050251.
  6. ↑ Morcos L, Ge B, Koka V, Lam KC, Pokholok DK, Gunderson KL, et al. (2011). "Genome-wide assessment of imprinted expression in human cells". Genome Biology. 12 (3): R25. doi: 10.1186/gb-2011-12-3-r25 . PMC   3129675 . PMID   21418647.
  7. ↑ Martienssen RA, Colot V (August 2001). "DNA methylation and epigenetic inheritance in plants and filamentous fungi". Science. 293 (5532): 1070–1074. doi:10.1126/science.293.5532.1070. PMID   11498574.
  8. ↑ Feil R, Berger F (April 2007). "Convergent evolution of genomic imprinting in plants and mammals". Trends in Genetics. 23 (4): 192–199. doi:10.1016/j.tig.2007.02.004. PMID   17316885.
  9. 1 2 3 Peters J (August 2014). "The role of genomic imprinting in biology and disease: an expanding view". Nature Reviews. Genetics. 15 (8): 517–530. doi:10.1038/nrg3766. PMID   24958438. S2CID   498562.
  10. ↑ Tucci V; Isles AR; Kelsey G; Ferguson-Smith AC (February 2019). "Genomic Imprinting and Physiological Processes in Mammals". Cell. 176 (5): 952–965. doi: 10.1016/j.cell.2019.01.043 . PMID   30794780.
  11. ↑ Preston, Elizabeth (13 February 2024). "Self-Love Is Important, but We Mammals Are Stuck With Sex - Some female birds, reptiles and other animals can make a baby on their own. But for mammals like us, eggs and sperm need each other". The New York Times . Archived from the original on 13 February 2024. Retrieved 16 February 2024.
  12. 1 2 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.
  13. ↑ "Can you generate offspring from two eggs?". 27 December 2021.
  14. ↑ Butler MG (October 2009). "Genomic imprinting disorders in humans: a mini-review". Journal of Assisted Reproduction and Genetics. 26 (9–10): 477–486. doi:10.1007/s10815-009-9353-3. PMC   2788689 . PMID   19844787.
  15. 1 2 Schrader F (1921). "The chromosomes in Pseudococcus nipæ". Biological Bulletin. 40 (5): 259–270. doi:10.2307/1536736. JSTOR   1536736 . Retrieved 2008-07-01.
  16. 1 2 Brown SW, Nur U (July 1964). "Heterochromatic Chromosomes in the Coccids". Science. 145 (3628): 130–136. Bibcode:1964Sci...145..130B. doi:10.1126/science.145.3628.130. PMID   14171547.
  17. 1 2 Hughes-Schrader S (1948). Cytology of Coccids (Coccoïdea-Homoptera). Advances in Genetics. Vol. 35. pp. 127–203. doi:10.1016/S0065-2660(08)60468-X. ISBN   9780120176021. PMID   18103373.
  18. 1 2 Nur U (1990). "Heterochromatization and euchromatization of whole genomes in scale insects (Coccoidea: Homoptera)". Development. 108: 29–34. doi:10.1242/dev.108.Supplement.29. PMID   2090427.
  19. ↑ 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.
  20. ↑ Barton SC, Surani MA, Norris ML (1984). "Role of paternal and maternal genomes in mouse development". Nature. 311 (5984): 374–376. Bibcode:1984Natur.311..374B. doi:10.1038/311374a0. PMID   6482961. S2CID   4321070. Closed Access logo transparent.svg
  21. ↑ Mann JR, Lovell-Badge RH (1984). "Inviability of parthenogenones is determined by pronuclei, not egg cytoplasm". Nature. 310 (5972): 66–67. Bibcode:1984Natur.310...66M. doi:10.1038/310066a0. PMID   6738704. S2CID   4336389.
  22. ↑ McGrath J, Solter D (May 1984). "Completion of mouse embryogenesis requires both the maternal and paternal genomes". Cell. 37 (1): 179–183. doi: 10.1016/0092-8674(84)90313-1 . PMID   6722870.
  23. ↑ Sagi I, Bar S, Benvenisty N (November 2018). "Mice from Same-Sex Parents: CRISPRing Out the Barriers for Unisexual Reproduction". Cell Stem Cell. 23 (5): 625–627. doi: 10.1016/j.stem.2018.10.012 . PMID   30388415. S2CID   53252140.
  24. ↑ Li ZK, Wang LY, Wang LB, Feng GH, Yuan XW, Liu C, et al. (November 2018). "Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions". Cell Stem Cell. 23 (5): 665–676.e4. doi: 10.1016/j.stem.2018.09.004 . PMID   30318303. S2CID   205251810.
  25. ↑ Wei Y, Yang CR, Zhao ZA (March 2022). "Viable offspring derived from single unfertilized mammalian oocytes". Proceedings of the National Academy of Sciences of the United States of America. 119 (12): e2115248119. Bibcode:2022PNAS..11915248W. doi: 10.1073/pnas.2115248119 . PMC   8944925 . PMID   35254875.
  26. ↑ Ledford, Heidi; Kozlov, Max (2023-03-09). "The mice with two dads: scientists create eggs from male cells" . Nature. 615 (7952): 379–380. Bibcode:2023Natur.615..379L. doi:10.1038/d41586-023-00717-7. PMID   36894725. S2CID   257428648.
  27. 1 2 Isles AR, Holland AJ (January 2005). "Imprinted genes and mother-offspring interactions". Early Human Development. 81 (1): 73–77. doi:10.1016/j.earlhumdev.2004.10.006. PMID   15707717.
  28. ↑ Morison IM, Ramsay JP, Spencer HG (August 2005). "A census of mammalian imprinting". Trends in Genetics. 21 (8): 457–465. doi:10.1016/j.tig.2005.06.008. PMID   15990197.
  29. ↑ Reik W; Lewis A (May 2005). "Co-evolution of X-chromosome inactivation and imprinting in mammals". Nature Reviews. Genetics. 6 (5): 403–410. doi:10.1038/nrg1602. PMID   15818385. S2CID   21091004.
  30. ↑ "Gene Tug-of-War Leads to Distinct Species". Howard Hughes Medical Institute. 2000-04-30. Archived from the original on 2013-03-28. Retrieved 2008-07-02.
  31. ↑ Bischoff SR, Tsai S, Hardison N, Motsinger-Reif AA, Freking BA, Nonneman D, et al. (November 2009). "Characterization of conserved and nonconserved imprinted genes in swine". Biology of Reproduction. 81 (5): 906–920. doi:10.1095/biolreprod.109.078139. PMC   2770020 . PMID   19571260.
  32. ↑ 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): 643–648. Bibcode:2010Sci...329..643G. doi:10.1126/science.1190830. PMC   3005244 . PMID   20616232.
  33. ↑ Hayden EC (April 2012). "RNA studies under fire". Nature. 484 (7395): 428. Bibcode:2012Natur.484..428C. doi: 10.1038/484428a . PMID   22538578.
  34. ↑ 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.
  35. 1 2 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.
  36. ↑ Magee DA, Sikora KM, Berkowicz EW, Berry DP, Howard DJ, Mullen MP, et al. (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.
  37. ↑ Cattanach BM, Kirk M (1985). "Differential activity of maternally and paternally derived chromosome regions in mice". Nature. 315 (6019): 496–498. Bibcode:1985Natur.315..496C. doi:10.1038/315496a0. PMID   4000278. S2CID   4337753.
  38. ↑ 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): 265–270. doi:10.1242/dev.122.1.265. PMID   8565838.
  39. ↑ Beechey C, Cattanach BM, Lake A, Peters J (2008). "Mouse Imprinting Data and References". MRC Harwell. Archived from the original on 2012-07-03. Retrieved 2008-07-02.
  40. ↑ 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.
  41. ↑ Kobayashi H, Yamada K, Morita S, Hiura H, Fukuda A, Kagami M, et al. (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): 461–472. doi: 10.1016/j.ygeno.2008.12.012 . PMID   19200453.
  42. ↑ Bjornsson HT, Albert TJ, Ladd-Acosta CM, Green RD, Rongione MA, Middle CM, et al. (May 2008). "SNP-specific array-based allele-specific expression analysis". Genome Research. 18 (5): 771–779. doi:10.1101/gr.073254.107. PMC   2336807 . PMID   18369178.
  43. ↑ Babak T, Deveale B, Armour C, Raymond C, Cleary MA, van der Kooy D, et al. (November 2008). "Global survey of genomic imprinting by transcriptome sequencing". Current Biology. 18 (22): 1735–1741. Bibcode:2008CBio...18.1735B. doi: 10.1016/j.cub.2008.09.044 . PMID   19026546. S2CID   10143690.
  44. ↑ 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): 1723–1730. doi:10.1101/gr.6584707. PMC   2099581 . PMID   18055845.
  45. ↑ Reik W; Dean W; Walter J (August 2001). "Epigenetic reprogramming in mammalian development". Science. 293 (5532): 1089–1093. doi:10.1126/science.1063443. PMID   11498579. S2CID   17089710.
  46. ↑ Court F, Tayama C, Romanelli V, Martin-Trujillo A, Iglesias-Platas I, Okamura K, et al. (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): 554–569. doi:10.1101/gr.164913.113. PMC   3975056 . PMID   24402520.
  47. ↑ 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): 1268–1282. doi:10.1101/gad.1416906. PMC   1472902 . PMID   16702402.
  48. ↑ Jin B, Li Y, Robertson KD (June 2011). "DNA methylation: superior or subordinate in the epigenetic hierarchy?". Genes & Cancer. 2 (6): 607–617. doi:10.1177/1947601910393957. PMC   3174260 . PMID   21941617.
  49. ↑ Metz CW (1938). "Chromosome behavior, inheritance and sex determination in Sciara". American Naturalist . 72 (743): 485–520. doi:10.1086/280803. JSTOR   2457532. S2CID   83550755.
  50. ↑ Alleman M, Doctor J (June 2000). "Genomic imprinting in plants: observations and evolutionary implications". Plant Molecular Biology. 43 (2–3): 147–161. doi:10.1023/A:1006419025155. PMID   10999401. S2CID   9499846.
  51. 1 2 Tycko B, Morison IM (September 2002). "Physiological functions of imprinted genes". Journal of Cellular Physiology. 192 (3): 245–258. doi: 10.1002/jcp.10129 . PMID   12124770. S2CID   42971427.
  52. ↑ 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.
  53. 1 2 Moore T, Haig D (February 1991). "Genomic imprinting in mammalian development: a parental tug-of-war". Trends in Genetics. 7 (2): 45–49. doi:10.1016/0168-9525(91)90230-N. PMID   2035190.
  54. ↑ Haig D (November 1997). "Parental antagonism, relatedness asymmetries, and genomic imprinting". Proceedings. Biological Sciences. 264 (1388): 1657–1662. Bibcode:1997RSPSB.264.1657H. doi:10.1098/rspb.1997.0230. PMC   1688715 . PMID   9404029.
  55. ↑ 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.
  56. ↑ 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.
  57. ↑ 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): 305–312. doi:10.1159/000103192. PMID   17675872. S2CID   27834663.
  58. 1 2 O'Connell MJ, Loughran NB, Walsh TA, Donoghue MT, Schmid KJ, Spillane C (October 2010). "A phylogenetic approach to test for evidence of parental conflict or gene duplications associated with protein-encoding imprinted orthologous genes in placental mammals". Mammalian Genome. 21 (9–10): 486–498. doi:10.1007/s00335-010-9283-5. PMID   20931201. S2CID   6883377.
  59. 1 2 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. S2CID   10697086. Archived from the original (PDF) on 2010-06-22. Retrieved 2011-01-06.
  60. ↑ Wolf JB (May 2009). "Cytonuclear interactions can favor the evolution of genomic imprinting". Evolution; International Journal of Organic Evolution. 63 (5): 1364–1371. doi:10.1111/j.1558-5646.2009.00632.x. PMID   19425202. S2CID   29251471.
  61. 1 2 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): 573–579. doi:10.1016/S0168-9525(00)02134-X. PMID   11102708.
  62. 1 2 de la Casa-Esperón E, Sapienza C (2003). "Natural selection and the evolution of genome imprinting". Annual Review of Genetics. 37: 349–370. doi:10.1146/annurev.genet.37.110801.143741. PMID   14616065.
  63. ↑ Barlow DP (April 1993). "Methylation and imprinting: from host defense to gene regulation?". Science. 260 (5106): 309–310. Bibcode:1993Sci...260..309B. doi:10.1126/science.8469984. PMID   8469984. S2CID   6925971.
  64. ↑ 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): 813–821. doi:10.1007/s00335-001-2083-1. PMID   11845283. S2CID   13419814.
  65. 1 2 3 4 Lawson HA, Cheverud JM, Wolf JB (September 2013). "Genomic imprinting and parent-of-origin effects on complex traits". Nature Reviews. Genetics. 14 (9): 609–617. doi:10.1038/nrg3543. PMC   3926806 . PMID   23917626.
  66. ↑ de Koning DJ, Rattink AP, Harlizius B, van Arendonk JA, Brascamp EW, Groenen MA (July 2000). "Genome-wide scan for body composition in pigs reveals important role of imprinting". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 7947–7950. Bibcode:2000PNAS...97.7947D. doi: 10.1073/pnas.140216397 . PMC   16650 . PMID   10859367.
  67. 1 2 Hoeschele I (2004-07-15). "Mapping Quantitative Trait Loci in Outbred Pedigrees". Handbook of Statistical Genetics. John Wiley & Sons, Ltd. doi:10.1002/0470022620.bbc17. ISBN   0-470-02262-0.
  68. ↑ Wolf JB, Cheverud JM, Roseman C, Hager R (June 2008). "Genome-wide analysis reveals a complex pattern of genomic imprinting in mice". PLOS Genetics. 4 (6): e1000091. doi: 10.1371/journal.pgen.1000091 . PMC   2390766 . PMID   18535661.
  69. ↑ Winstead ER (2001-05-07). "The Legacy of Solid Gold". Genome News Network.
  70. ↑ 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): 840–852. doi: 10.1093/humupd/dmu033 . PMID   24961233.
  71. 1 2 Rotondo JC, Selvatici R, Di Domenico M, Marci R, Vesce F, Tognon M, Martini F (September 2013). "Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males". Epigenetics. 8 (9): 990–997. doi:10.4161/epi.25798. PMC   3883776 . PMID   23975186.
  72. ↑ Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, et al. (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): 214–219. Bibcode:1999PNAS...96..214Y. doi: 10.1073/pnas.96.1.214 . PMC   15119 . PMID   9874798.
  73. ↑ Allis CD, Jenuwein T, Reinberg D (2007). Epigenetics. CSHL Press. p. 440. ISBN   978-0-87969-724-2 . Retrieved 10 November 2010.
  74. ↑ Scharfmann R (2007). Development of the Pancreas and Neonatal Diabetes. Karger Publishers. pp. 113–. ISBN   978-3-8055-8385-5 . Retrieved 10 November 2010.
  75. ↑ Herrick G, Seger J (1999). "Imprinting and Paternal Genome Elimination in Insects". In Ohlsson R (ed.). Genomic Imprinting. Results and Problems in Cell Differentiation. Vol. 25. Springer Berlin Heidelberg. pp. 41–71. doi:10.1007/978-3-540-69111-2_3. ISBN   978-3-662-21956-0. PMID   10339741.
  76. ↑ Bresnahan et al., "Examining parent-of-origin effects on transcription and RNA methylation in mediating aggressive behavior in honey bees (Apis mellifera)", BMC Genomics 24: 315 (2023), https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-023-09411-4
  77. ↑ 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. S2CID   14643386.
  78. ↑ Magee DA, Berry DP, Berkowicz EW, Sikora KM, Howard DJ, Mullen MP, et al. (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.
  79. ↑ Sikora KM, Magee DA, Berkowicz EW, Berry DP, Howard DJ, Mullen MP, et al. (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.
  80. ↑ Berkowicz EW, Magee DA, Sikora KM, Berry DP, Howard DJ, Mullen MP, et al. (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.
  81. ↑ Bonthuis PJ, Steinwand S, Stacher Hörndli CN, Emery J, Huang WC, Kravitz S, et al. (March 2022). "Noncanonical genomic imprinting in the monoamine system determines naturalistic foraging and brain-adrenal axis functions". Cell Reports. 38 (10): 110500. doi:10.1016/j.celrep.2022.110500. PMC   9128000 . PMID   35263575.
  82. ↑ Robitzski D (12 April 2022). "Mouse Foraging Behavior Shaped by Opposite-Sex Parent's Genes". The Scientist.
  83. ↑ 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.
  84. ↑ 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): 312–315. Bibcode:2007Natur.447..312N. doi:10.1038/nature05770. hdl: 11858/00-001M-0000-0012-3877-6 . PMID   17468744. S2CID   4396777.
  85. ↑ 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): 142–148. doi:10.1016/j.tig.2009.12.006. PMID   20089326.
  86. ↑ Picard CL, Gehring M (2020). "Identification and Comparison of Imprinted Genes Across Plant Species". In Spillane C, McKeown P (eds.). Plant Epigenetics and Epigenomics. Methods in Molecular Biology. Vol. 2093. New York, NY: Springer US. pp. 173–201. doi:10.1007/978-1-0716-0179-2_13. ISBN   978-1-0716-0178-5. PMID   32088897. S2CID   211261218.
  87. ↑ Wyder S, Raissig MT, Grossniklaus U (February 2019). "Consistent Reanalysis of Genome-wide Imprinting Studies in Plants Using Generalized Linear Models Increases Concordance across Datasets". Scientific Reports. 9 (1): 1320. Bibcode:2019NatSR...9.1320W. doi:10.1038/s41598-018-36768-4. PMC   6362150 . PMID   30718537.
  88. ↑ Anderson SN, Zhou P, Higgins K, Brandvain Y, Springer NM (April 2021). "Widespread imprinting of transposable elements and variable genes in the maize endosperm". PLOS Genetics. 17 (4): e1009491. doi: 10.1371/journal.pgen.1009491 . PMC   8057601 . PMID   33830994.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.