Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the mother or the father. 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. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. In 2014, there were about 150 imprinted genes known in mice and about half that in humans. As of 2019, 260 imprinted genes have been reported in mice and 228 in humans.
Prader–Willi syndrome (PWS) is a genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become constantly hungry, which often leads to obesity and type 2 diabetes. Mild to moderate intellectual impairment and behavioral problems are also typical of the disorder. Often, affected individuals have a narrow forehead, small hands and feet, short height, and light skin and hair. Most are unable to have children.
Chromosome 15q partial deletion is a rare human genetic disorder, caused by a chromosomal aberration in which the long ("q") arm of one copy of chromosome 15 is deleted, or partially deleted. Like other chromosomal disorders, this increases the risk of birth defects, developmental delay and learning difficulties, however, the problems that can develop depend very much on what genetic material is missing. If the mother's copy of the chromosomal region 15q11-13 is deleted, Angelman syndrome (AS) can result. The sister syndrome Prader-Willi syndrome (PWS) can result if the father's copy of the chromosomal region 15q11-13 is deleted. The smallest observed region that can result in these syndromes when deleted is therefore called the PWS/AS critical region. In addition to deletions, uniparental disomy of chromosome 15 also gives rise to the same genetic disorders, indicating that genomic imprinting must occur in this region.
In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome. Some chromosomes have fragile spots where breaks occur which result in the deletion of a part of chromosome. The breaks can be induced by heat, viruses, radiations, chemicals. When a chromosome breaks, a part of it is deleted or lost, the missing piece of chromosome is referred to as deletion or a deficiency.
Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other. UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent or isodisomy, in which a single chromosome from one parent is duplicated. Uniparental disomy may have clinical relevance for several reasons. For example, either isodisomy or heterodisomy can disrupt parent-specific genomic imprinting, resulting in imprinting disorders. Additionally, isodisomy leads to large blocks of homozygosity, which may lead to the uncovering of recessive genes, a similar phenomenon seen in inbred children of consanguineous partners.
Wolf–Hirschhorn syndrome (WHS) is a chromosomal deletion syndrome resulting from a partial deletion on the short arm of chromosome 4. Features include a distinct craniofacial phenotype and intellectual disability.
Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells.
Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 99.7 million base pairs and represents between 3% and 3.5% of the total DNA in cells. Chromosome 15 is an acrocentric chromosome, with a very small short arm, which contains few protein coding genes among its 19 million base pairs. It has a larger long arm that is gene rich, spanning about 83 million base pairs.
In molecular biology, SNORD116 is a non-coding RNA (ncRNA) molecule which functions in the modification of other small nuclear RNAs (snRNAs). This type of modifying RNA is usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis. It is known as a small nucleolar RNA (snoRNA) and also often referred to as a guide RNA.
Trisomic rescue is a genetic phenomenon in which a fertilized ovum containing three copies of a chromosome loses one of these chromosomes to form a diploid chromosome complement. If both of the retained chromosomes come from the same parent, then uniparental disomy results. If the retained chromosomes come from different parents then there are no phenotypic or genotypic anomalies. The mechanism of trisomic rescue has been well confirmed in vivo, and alternative mechanisms that occur in trisomies are rare in comparison.
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.
Small nuclear ribonucleoprotein-associated protein N is a protein that in humans is encoded by the SNRPN gene.
Angelman syndrome or Angelman's syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.
In molecular biology, Small nucleolar RNA SNORD113 is a small nucleolar RNA molecule which is located in the imprinted human 14q32 locus and may play a role in the evolution and/or mechanism of the epigenetic imprinting process.
Silver–Russell syndrome (SRS), also called Silver–Russell dwarfism, is a rare congenital growth disorder. In the United States it is usually referred to as Russell–Silver syndrome (RSS), and Silver–Russell syndrome elsewhere. It is one of 200 types of dwarfism and one of five types of primordial dwarfism.
The imprinted brain hypothesis is an unsubstantiated hypothesis in evolutionary psychology regarding the causes of autism spectrum and schizophrenia spectrum disorders, first presented by Bernard Crespi and Christopher Badcock in 2008. It claims that certain autistic and schizotypal traits are opposites, and that this implies the etiology of the two conditions must be at odds.
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.
Arthur L. Beaudet is a founder and CEO of Luna Genetics. He is a past professor and chair of molecular and human genetics at Baylor College of Medicine. He was inducted into the Institute of Medicine in 1995, the Society of Scholars in 2008 and into the National Academy of Sciences in 2011.
A microdeletion syndrome is a syndrome caused by a chromosomal deletion smaller than 5 million base pairs spanning several genes that is too small to be detected by conventional cytogenetic methods or high resolution karyotyping. Detection is done by fluorescence in situ hybridization (FISH). Larger chromosomal deletion syndromes are detectable using karyotyping techniques.
Intragenomic and intrauterine conflicts in humans arise between mothers and their offspring. Parental investment theory states that parents and their offspring will often be in conflict over the optimal amount of investment that the parent should provide. This is because the best interests of the parent do not always match the best interests of the offspring. Maternal-infant conflict is of interest due to the intensity of maternal investment in her offspring. In humans, mothers often invest years of care into their children due to the long developmental period before children become self-sufficient.
