An isochromosome is an unbalanced structural abnormality in which the arms of the chromosome are mirror images of each other. [1] The chromosome consists of two copies of either the long (q) arm or the short (p) arm because isochromosome formation is equivalent to a simultaneous duplication and deletion of genetic material. Consequently, there is partial trisomy of the genes present in the isochromosome and partial monosomy of the genes in the lost arm. [2]
An isochromosome can be abbreviated as i(chromosome number)(centromeric breakpoint). For example, an isochromosome of chromosome 17 containing two q arms can be identified as i(17)(q10).(Medulloblastoma)
Isochromosomes can be created during mitosis and meiosis through a misdivision of the centromere or U-type strand exchange. [1]
Under normal separation of sister chromatids in anaphase, the centromere will divide longitudinally, or parallel to the long axis of the chromosome. [3] An isochromosome is created when the centromere is divided transversely, or perpendicular to the long axis of the chromosome. The division is usually not occurring in the centromere itself, but in an area surrounding the centromere, also known as a pericentric region. [2] It is proposed that these sites of exchange contain homologous sequences between sister chromatids. [4] Although the resulting chromosome may appear monocentric with only one centromere, it is isodicentric with two centromeres very close to each other; resulting in a potential loss of genetic material found on the other arms. [2] [4] Misdivision of the centromere can also produce monocentric isochromosomes, but they are not as common as dicentric isochromosomes. [1]
A more common mechanism in the formation of isochromosomes is through the breakage and fusion of sister chromatids, most likely occurring in early anaphase of mitosis or meiosis. [3] A double-stranded break in the pericentric region of the chromosome is repaired when the sister chromatids, each containing a centromere, are fused together. [2] This U-type exchange of genetic material creates an isodicentric chromosome. [5] Misdivision of the centromere and U-type exchange can occur in sister chromatids, thus creating an isochromosome with genetically identical arms. However, U-type exchange can also occur for homologous chromosomes which creates an isochromosome with homologous arms. This exchange between homologues is most likely due to homologous sequences containing low copy repeats. Regardless of the chromosome involved in U-type exchange, the acentric fragment of the chromosome is lost, thus creating a partial monosomy of genes located in that portion of the acentric chromosome. [2]
The most common isochromosome is the X sex chromosome. [4] Acrocentric autosomal chromosomes 13, 14, 15, 21, and 22 are also common candidates for isochromosome formation. [1] Chromosomes containing smaller arms are more likely to become isochromosomes because the loss of genetic material in those arms can be tolerated. [2]
Turner syndrome is a condition in females in which there is partial or complete loss of one X chromosome. This causes symptoms such as growth and sexual development problems. In 15% of Turner syndrome patients, the structural abnormality is isochromosome X, which is composed of two copies of the q arm (i(Xq)). [1] [2] A majority of i(Xq) are created by U-type strand exchange. A breakage and reunion in the pericentric region of the p arm results in a dicentric isochromosome. [4] Some of the p arm can be found in this formation of i(Xq), but a majority of the genetic material on the p arm is lost so it is considered absent. Since the p-arm of the X chromosome contains genes that are necessary for normal sexual development, Turner's syndrome patients experience phenotypic effects. [3] Alternatively, the increase in dosage of genes on the q arm may be involved in a 10-fold increase in risk of i(Xq) Turner's patients developing autoimmune thyroiditis, a disease in which the body creates antibodies to target and destroy thyroid cells. [6]
Neoplasia is uncontrolled cell growth, resulting in the creation of a tumour. In many different forms of neoplasia, isochromosome 17q is the most frequent neoplasia associated isochromosome and corresponds with poor patient survival. [7] [8] Unique DNA sequences, known as low copy repeats, occur in the pericentric region of the p arm, so a crossover event in that area can create a dicentric isochromosome through U-type strand exchange. [9] The neoplasia created from i(17q) is caused by a decrease and increase in gene dosage from the monosomy of the p arm and trisomy of the q arm, respectively. Many candidate tumour suppressor genes are found on the lost p arm, allowing the tumour cell population to be maintained. [8] It is debated whether the loss of tumour suppressor gene p53, located on 17p, is involved in the central pathogenesis of some neoplasia. The presence of one p53 gene can be functionally active, but its relation to other oncogenes can alter its expression levels when present only in one copy. [7] [8] [9] Since the genetic sequences involved in i(17q) neoplasia are large, it is difficult to determine which genes, or combination of genes, are involved in tumour growth.
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. Most eukaryotic chromosomes include packaging proteins called histones which, aided by chaperone proteins, bind to and condense the DNA molecule to maintain its integrity. These chromosomes display a complex three-dimensional structure, which plays a significant role in transcriptional regulation.
The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers attach to the centromere via the kinetochore.
Meiosis is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and female will fuse to create a cell with two copies of each chromosome again, the zygote.
Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hairline at the back of the neck, short stature, and swollen hands and feet are seen at birth. Typically, those affected do not develop menstrual periods, or breasts without hormone treatment and are unable to have children without reproductive technology. Heart defects, diabetes, and low thyroid hormone occur in the disorder more frequently than average. Most people with TS have normal intelligence; however, many have problems with spatial visualization that may be needed in order to learn mathematics. Vision and hearing problems also occur more often than average.
Prophase is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reticulum and the disappearance of the nucleolus.
A chromatid is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chromatids. During the later stages of cell division these chromatids separate longitudinally to become individual chromosomes.
A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci where they provide points along each chromosome which enable a pair of chromosomes to align correctly with each other before separating during meiosis. This is the basis for Mendelian inheritance which characterizes inheritance patterns of genetic material from an organism to its offspring parent developmental cell at the given time and area.
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Two detached fragments of two different chromosomes are switched. Robertsonian translocation occurs when two non-homologous chromosomes get attached, meaning that given two healthy pairs of chromosomes, one of each pair "sticks" and blends together homogeneously.
Robertsonian translocation (ROB) is a chromosomal abnormality wherein a certain type of a chromosome becomes attached to another. It is the most common form of chromosomal translocation in humans, affecting 1 out of every 1,000 babies born. It does not usually cause health difficulties, but can in some cases result in genetic disorders such as Down syndrome and Patau syndrome. Robertsonian translocations result in a reduction in the number of chromosomes.
An inversion is a chromosome rearrangement in which a segment of a chromosome is reversed end-to-end. An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself. Inversions are of two types: paracentric and pericentric.
A small supernumerary marker chromosome (sSMC) is an abnormal extra chromosome. It contains copies of parts of one or more normal chromosomes and like normal chromosomes is located in the cell's nucleus, is replicated and distributed into each daughter cell during cell division, and typically has genes which may be expressed. However, it may also be active in causing birth defects and neoplasms. The sSMC's small size makes it virtually undetectable using classical cytogenetic methods: the far larger DNA and gene content of the cell's normal chromosomes obscures those of the sSMC. Newer molecular techniques such as fluorescence in situ hybridization, next generation sequencing, comparative genomic hybridization, and highly specialized cytogenetic G banding analyses are required to study it. Using these methods, the DNA sequences and genes in sSMCs are identified and help define as well as explain any effect(s) it may have on individuals.
A sister chromatid refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the duplicated chromosome. A pair of sister chromatids is called a dyad. A full set of sister chromatids is created during the synthesis (S) phase of interphase, when all the chromosomes in a cell are replicated. The two sister chromatids are separated from each other into two different cells during mitosis or during the second division of meiosis.
A dicentric chromosome is an abnormal chromosome with two centromeres. It is formed through the fusion of two chromosome segments, each with a centromere, resulting in the loss of acentric fragments and the formation of dicentric fragments. The formation of dicentric chromosomes has been attributed to genetic processes, such as Robertsonian translocation and paracentric inversion. Dicentric chromosomes have important roles in the mitotic stability of chromosomes and the formation of pseudodicentric chromosomes. Their existence has been linked to certain natural phenomena such as irradiation and have been documented to underlie certain clinical syndromes, notably Kabuki syndrome. The formation of dicentric chromosomes and their implications on centromere function are studied in certain clinical cytogenetics laboratories.
A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene. Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. Chromosome abnormalities may be detected or confirmed by comparing an individual's karyotype, or full set of chromosomes, to a typical karyotype for the species via genetic testing.
18p- is a genetic condition caused by a deletion of all or part of the short arm of chromosome 18. It occurs in about 1 of every 50,000 births.
Tetrasomy 9p is a rare chromosomal disorder characterized by the presence of two extra copies of the short arm of chromosome 9, in addition to the usual two. Symptoms of tetrasomy 9p vary widely among affected individuals but typically include varying degrees of delayed growth, abnormal facial features and intellectual disability. Symptoms of the disorder are comparable to those of trisomy 9p.
Unequal crossing over is a type of gene duplication or deletion event that deletes a sequence in one strand and replaces it with a duplication from its sister chromatid in mitosis or from its homologous chromosome during meiosis. It is a type of chromosomal crossover between homologous sequences that are not paired precisely. Normally genes are responsible for occurrence of crossing over. It exchanges sequences of different links between chromosomes. Along with gene conversion, it is believed to be the main driver for the generation of gene duplications and is a source of mutation in the genome.
Ring chromosome 18 is a genetic condition caused by a deletion of the two ends of chromosome 18 followed by the formation of a ring-shaped chromosome. It was first reported in 1964.
13q deletion syndrome is a rare genetic disease caused by the deletion of some or all of the large arm of human chromosome 13. Depending upon the size and location of the deletion on chromosome 13, the physical and mental manifestations will vary. It has the potential to cause intellectual disability and congenital malformations that affect a variety of organ systems. Because of the rarity of the disease in addition to the variations in the disease, the specific genes that cause this disease are unknown. This disease is also known as:
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