Loss of heterozygosity
Loss of heterozygosity is a cross chromosomal event that results in loss of the entire gene and the surrounding chromosomal region. All diploid cells, for example most human somatic cells, contain two copies of the genome, one from each parent. For the majority of positions in the genome the base present is consistent between individuals, however a small percentage may contain different bases and these positions are called ‘single nucleotide polymorphisms’ or ‘SNPs’; when the genomic copies derived from each parent have different bases for these polymorphic regions the region is said to be heterozygous. Most of the chromosomes within somatic cells of individuals are paired, allowing for SNP locations to be heterozygous. However, one parental copy of a region can sometimes be lost, which results in the region having just one copy; the single copy cannot be heterozygous at SNP locations and therefore the region shows loss of heterozygosity. Loss of heterozygosity due to loss of one parental copy in a region is called hemizygosity in that region.
The loss of heterozygosity is a common occurrence in cancer, where it indicates the absence of a functional tumor suppressor gene in the lost region. However, many people remain healthy with such a loss, because there still is one functional gene left on the other chromosome of the chromosome pair; the remaining copy of the tumor suppressor gene can be inactivated by a point mutation, leaving no tumor suppressor gene to protect the body. Loss of heterozygosity does not imply a homozygous state. First Hit: The first hit is classically thought of as a point mutation, but arises due to epigenetic events which inactivate one copy of a tumor suppressor gene, such as Rb1. In hereditary cancer syndromes, individuals are born with the first hit; the individual does not develop cancer at this point because the remaining TSG allele on the other locus is still functioning normally. Second Hit: While the second hit is assumed to be a deletion that results in loss of the remaining functioning TSG allele, the original published mechanism of RB1 LOH was mitotic recombination/gene conversion/copy-neutral LOH, not deletion.
There is a critical difference between deletion and CN-LOH, as the latter mechanism cannot be detected by comparative genomic hybridization -based gene copy number counting, requires allelic genotyping. Either way, LOH leaves only non-functioning alleles of the TSG, the individual goes on to develop cancer. Copy-neutral LOH is thus called because no net change in the copy number occurs in the affected individual. Possible causes for copy-neutral LOH include acquired uniparental gene conversion. In UPD, a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent due to errors in meiosis I or meiosis II; this acquired homozygosity could lead to development of cancer if the individual inherited a non-functional allele of a tumor suppressor gene. In tumor cells copy-neutral LOH can be biologically equivalent to the second hit in the Knudson hypothesis. Acquired UPD is quite common in both hematologic and solid tumors, is reported to constitute 20 to 80% of the LOH seen in human tumors.
Determination of virtual karyotypes using SNP-based arrays can provide genome-wide copy number and LOH status, including detection of copy-neutral LOH. Copy-neutral LOH can not be detected by FISH, or conventional cytogenetics. SNP-based arrays are preferred for virtual karyotyping of tumors and can be performed on fresh or paraffin-embedded tissues; the classical example of such a loss of protecting genes is hereditary retinoblastoma, in which one parent's contribution of the tumor suppressor Rb1 is flawed. Although most cells will have a functional second copy, chance loss of heterozygosity events in individual cells invariably lead to the development of this retinal cancer in the young child; the genes BRCA1 and BRCA2 show loss of heterozygosity in samplings of tumors from patients who have germline mutations. BRCA1/2 are genes that produce proteins which regulate the DNA repair pathway by binding to Rad51. Loss of heterozygosity can be identified in cancers by noting the presence of heterozygosity at a genetic locus in an organism's germline DNA, the absence of heterozygosity at that locus in the cancer cells.
This is done using polymorphic markers, such as microsatellites or single-nucleotide polymorphisms, for which the two parents contributed different alleles. Genome-wide LOH status of fresh or paraffin embedded tissue samples can be assessed by virtual karyotyping using SNP arrays, it has been proposed. The minor allele in heterozygous areas of the genome is to have mild fitness consequences compared to de-novo mutations because selection has had time to remove deleterious alleles; when allelic gene conversion removes the major allele at these sites organisms are to experience a mild decline in fitness. Because LOH is much more common than de-novo mutation, because the fitness consequences are closer to neutrality, this process should drive Muller's ratchet more than de-novo mutations. While this process has received little experimental investigation, it is known that major signature of asexuality in metazoan genomes appears to be genome wide LOH, a sort of anti-meselson effect. Microsatellite instability Tumor suppressor gene Virtual Karyotype Knudson hypothesis Deletion "Long-term study of the clinical significance of loss of heterozygosity i
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 meiosis. Homologs have the same genes in the same loci where they provide points along each chromosome which enable a pair of chromosomes to align 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. Chromosomes are linear arrangements of condensed deoxyribonucleic acid and histone proteins, which form a complex called chromatin. Homologous chromosomes are made up of chromosome pairs of the same length, centromere position, staining pattern, for genes with the same corresponding loci. One homologous chromosome is inherited from the organism's mother. After mitosis occurs within the daughter cells, they have the correct number of genes which are a mix of the two parents' genes.
In diploid organisms, the genome is composed of one set of each homologous chromosome pair, as compared to tetraploid organisms which may have two sets of each homologous chromosome pair. The alleles on the homologous chromosomes may be different, resulting in different phenotypes of the same genes; this mixing of maternal and paternal traits is enhanced by crossing over during meiosis, wherein lengths of chromosomal arms and the DNA they contain within a homologous chromosome pair are exchanged with one another. Early in the 1900s William Bateson and Reginald Punnett were studying genetic inheritance and they noted that some combinations of alleles appeared more than others; that data and information was further explored by Thomas Morgan. Using test cross experiments, he revealed that, for a single parent, the alleles of genes near to one another along the length of the chromosome move together. Using this logic he concluded that the two genes he was studying were located on homologous chromosomes.
On during the 1930s Harriet Creighton and Barbara McClintock were studying meiosis in corn cells and examining gene loci on corn chromosomes. Creighton and McClintock discovered that the new allele combinations present in the offspring and the event of crossing over were directly related; this proved interchromosomal genetic recombination. Homologous chromosomes are chromosomes which contain the same genes in the same order along their chromosomal arms. There are two main properties of homologous chromosomes: the length of chromosomal arms and the placement of the centromere; the actual length of the arm, in accordance with the gene locations, is critically important for proper alignment. Centromere placement can be characterized by four main arrangements, consisting of being either metacentric, acrocentric, or telocentric. Both of these properties are the main factors for creating structural homology between chromosomes. Therefore, when two chromosomes of the exact structure exist, they are able to pair together to form homologous chromosomes.
Since homologous chromosomes are not identical and do not originate from the same organism, they are different from sister chromatids. Sister chromatids result after DNA replication has occurred, thus are identical, side-by-side duplicates of each other. Humans have a total of 46 chromosomes, but there are only 22 pairs of homologous autosomal chromosomes; the additional 23rd pair is the sex chromosomes, X and Y. If this pair is made up of an X and Y chromosome the pair of chromosomes is not homologous because their size and gene content differ greatly; the 22 pairs of homologous chromosomes contain the same genes but code for different traits in their allelic forms since one was inherited from the mother and one from the father. So humans have two homologous chromosome sets in each cell, meaning humans are diploid organisms. Homologous chromosomes are important in the processes of mitosis, they allow for the recombination and random segregation of genetic material from the mother and father into new cells.
Meiosis is a round of two cell divisions that results in four haploid daughter cells that each contain half the number of chromosomes as the parent cell. It reduces the chromosome number in a germ cell by half by first separating the homologous chromosomes in meiosis I and the sister chromatids in meiosis II; the process of meiosis I is longer than meiosis II because it takes more time for the chromatin to replicate and for the homologous chromosomes to be properly oriented and segregated by the processes of pairing and synapsis in meiosis I. During meiosis, genetic recombination and crossing over produces daughter cells that each contain different combinations of maternally and paternally coded genes; this recombination of genes allows for the introduction of new allele pairings and genetic variation. Genetic variation among organisms helps make a population more stable by providing a wider range of genetic traits for natural selection to act on. In prophase I of meiosis I, each chromosome is aligned with its homologous partner and pairs completely.
In prophase I, the DNA has undergone replication so each chromosome consists of two identical chromatids connected by a common centromere. During the zygotene stage of prophase I, the homologous chromosomes pair up with each other; this pairing occurs by a synapsis process where the synaptonemal complex - a protein scaffold - is assembled and joins the homologous chromosomes along their lengths. Cohesin crosslinking occurs between the homologous chromosomes and helps them resist being pulled apart until anaphase. Genetic crossing-over, a type of recombination, occurs during the pachytene stage of prophase I
The X chromosome is one of the two sex-determining chromosomes in many organisms, including mammals, is found in both males and females. It is a part of the XY sex-determination X0 sex-determination system; the X chromosome was named for its unique properties by early researchers, which resulted in the naming of its counterpart Y chromosome, for the next letter in the alphabet, following its subsequent discovery. It was first noted. Henking was studying the testicles of Pyrrhocoris and noticed that one chromosome did not take part in meiosis. Chromosomes are so named because of their ability to take up staining. Although the X chromosome could be stained just as well as the others, Henking was unsure whether it was a different class of object and named it X element, which became X chromosome after it was established that it was indeed a chromosome; the idea that the X chromosome was named after its similarity to the letter "X" is mistaken. All chromosomes appear as an amorphous blob under the microscope and only take on a well defined shape during mitosis.
This shape is vaguely X-shaped for all chromosomes. It is coincidental that the Y chromosome, during mitosis, has two short branches which can look merged under the microscope and appear as the descender of a Y-shape, it was first suggested that the X chromosome was involved in sex determination by Clarence Erwin McClung in 1901. After comparing his work on locusts with Henking's and others, McClung noted that only half the sperm received an X chromosome, he called this chromosome an accessory chromosome, insisted that it was a proper chromosome, theorized that it was the male-determining chromosome. Luke Hutchison noticed that a number of possible ancestors on the X chromosome inheritance line at a given ancestral generation follows the Fibonacci sequence. A male individual has an X chromosome, which he received from his mother, a Y chromosome, which he received from his father; the male counts as the "origin" of his own X chromosome, at his parents' generation, his X chromosome came from a single parent.
The male's mother received one X chromosome from her mother, one from her father, so two grandparents contributed to the male descendant's X chromosome. The maternal grandfather received his X chromosome from his mother, the maternal grandmother received X chromosomes from both of her parents, so three great-grandparents contributed to the male descendant's X chromosome. Five great-great-grandparents contributed to the male descendant's X chromosome, etc; the X chromosome in humans spans more than 153 million base pairs. It represents about 800 protein-coding genes compared to the Y chromosome containing about 70 genes, out of 20,000–25,000 total genes in the human genome; each person has one pair of sex chromosomes in each cell. Females have two X chromosomes, whereas males have one Y chromosome. Both males and females retain one of their mother's X chromosomes, females retain their second X chromosome from their father. Since the father retains his X chromosome from his mother, a human female has one X chromosome from her paternal grandmother, one X chromosome from her mother.
This inheritance pattern follows the Fibonacci numbers at a given ancestral depth. Genetic disorders that are due to mutations in genes on the X chromosome are described as X linked. If X chromosome has a genetic disease gene, it always causes illness in male patients, since men have only one X chromosome and therefore only one copy of each gene. Females, may stay healthy and only be carrier of genetic illness, since they have another X chromosome and possibility to have healthy gene copy. For example hemophilia and red-green colorblindness run in family this way; the X chromosome carries hundreds of genes but few, if any, of these have anything to do directly with sex determination. Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in nearly all somatic cells; this phenomenon is called X-inactivation or Lyonization, creates a Barr body. If X-inactivation in the somatic cell meant a complete de-functionalizing of one of the X-chromosomes, it would ensure that females, like males, had only one functional copy of the X chromosome in each somatic cell.
This was assumed to be the case. However, recent research suggests that the Barr body may be more biologically active than was supposed; the partial inactivation of the X-chromosome is due to repressive heterochromatin that compacts the DNA and prevents the expression of most genes. Heterochromatin compaction is regulated by Polycomb Repressive Complex 2; the following are some of the gene count estimates of human X chromosome. Because researchers use different approaches to genome annotation their predictions of the number
Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are related genetically. By analogy, the term is used in human reproduction, but more refers to the genetic disorders and other consequences that may arise from expression of deleterious or recessive traits resulting from incestuous sexual relationships and consanguinity. Inbreeding results in homozygosity, which can increase the chances of offspring being affected by deleterious or recessive traits; this leads to at least temporarily decreased biological fitness of a population, its ability to survive and reproduce. An individual who inherits such deleterious traits is colloquially referred to as inbred; the avoidance of expression of such deleterious recessive alleles caused by inbreeding, via inbreeding avoidance mechanisms, is the main selective reason for outcrossing. Crossbreeding between populations often has positive effects on fitness-related traits, but sometimes leads to negative effects known as outbreeding depression.
However increased homozygosity increases probability of fixing beneficial alleles and slightly decreases probability of fixing deleterious alleles in population. Inbreeding can result in purging of deleterious alleles from a population through purifying selection. Inbreeding is a technique used in selective breeding. For example, in livestock breeding, breeders may use inbreeding when trying to establish a new and desirable trait in the stock and for producing distinct families within a breed, but will need to watch for undesirable characteristics in offspring, which can be eliminated through further selective breeding or culling. Inbreeding helps to ascertain the type of gene action affecting a trait. Inbreeding is used to reveal deleterious recessive alleles, which can be eliminated through assortative breeding or through culling. In plant breeding, inbred lines are used as stocks for the creation of hybrid lines to make use of the effects of heterosis. Inbreeding in plants occurs in the form of self-pollination.
Inbreeding can influence gene expression which can prevent inbreeding depression. Offspring of biologically related persons are subject to the possible effects of inbreeding, such as congenital birth defects; the chances of such disorders are increased when the biological parents are more related. This is because such pairings have a 25% probability of producing homozygous zygotes, resulting in offspring with two recessive alleles, which can produce disorders when these alleles are deleterious; because most recessive alleles are rare in populations, it is unlikely that two unrelated marriage partners will both be carriers of the same deleterious allele. It should be noted that for each homozygous recessive individual formed there is an equal chance of producing a homozygous dominant individual — one devoid of the harmful allele. Contrary to common belief, inbreeding does not in itself alter allele frequencies, but rather increases the relative proportion of homozygotes to heterozygotes. In the short term, incestuous reproduction is expected to increase the number of spontaneous abortions of zygotes, perinatal deaths, postnatal offspring with birth defects.
The advantages of inbreeding may be the result of a tendency to preserve the structures of alleles interacting at different loci that have been adapted together by a common selective history. Malformations or harmful traits can stay within a population due to a high homozygosity rate, this will cause a population to become fixed for certain traits, like having too many bones in an area, like the vertebral column of wolves on Isle Royale or having cranial abnormalities, such as in Northern elephant seals, where their cranial bone length in the lower mandibular tooth row has changed. Having a high homozygosity rate is problematic for a population because it will unmask recessive deleterious alleles generated by mutations, reduce heterozygote advantage, it is detrimental to the survival of small, endangered animal populations; when deleterious recessive alleles are unmasked due to the increased homozygosity generated by inbreeding, this can cause inbreeding depression. There may be other deleterious effects besides those caused by recessive diseases.
Thus, similar immune systems may be more vulnerable to infectious diseases. Inbreeding history of the population should be considered when discussing the variation in the severity of inbreeding depression between and within species. With persistent inbreeding, there is evidence that shows that inbreeding depression becomes less severe; this is associated with the unmasking and elimination of deleterious recessive alleles. However, inbreeding depression is not a temporary phenomenon because this elimination of deleterious recessive alleles will never be complete. Eliminating deleterious mutations through inbreeding under moderate selection is not as effective. Fixation of alleles most occurs through Muller's ratchet, when an asexual population's genome accumulates deleterious mutations that are irreversible. Despite all its disadvantages, inbreeding can have a variety of advantages, such as reducing the recombination load, allowing the expression of recessive advantageous phenotypes, it has been proposed th
Dominance in genetics is a relationship between alleles of one gene, in which the effect on phenotype of one allele masks the contribution of a second allele at the same locus. The first allele is dominant and the second allele is recessive. For genes on an autosome, the alleles and their associated traits are autosomal dominant or autosomal recessive. Dominance is a key concept in Mendelian inheritance and classical genetics; the dominant allele codes for a functional protein whereas the recessive allele does not. A classic example of dominance is the inheritance of seed shape in peas. Peas associated with allele r. In this case, three combinations of alleles are possible: RR, Rr, rr; the RR individuals have round peas and the rr individuals have wrinkled peas. In Rr individuals the R allele masks the presence of the r allele, so these individuals have round peas. Thus, allele R is dominant to allele r, allele r is recessive to allele R; this use of upper case letters for dominant alleles and lower case ones for recessive alleles is a followed convention.
More where a gene exists in two allelic versions, three combinations of alleles are possible: AA, Aa, aa. If AA and aa individuals show different forms of some trait, Aa individuals show the same phenotype as AA individuals allele A is said to dominate, be dominant to or show dominance to allele a, a is said to be recessive to A. Dominance is not inherent to either its phenotype, it is a relationship between two alleles of their associated phenotypes. An allele may be dominant for a particular aspect of phenotype but not for other aspects influenced by the same gene. Dominance differs from epistasis, a relationship in which an allele of one gene affects the expression of another allele at a different gene; the concept of dominance was introduced by Gregor Johann Mendel. Though Mendel, "The Father of Genetics", first used the term in the 1860s, it was not known until the early twentieth century. Mendel observed that, for a variety of traits of garden peas having to do with the appearance of seeds, seed pods, plants, there were two discrete phenotypes, such as round versus wrinkled seeds, yellow versus green seeds, red versus white flowers or tall versus short plants.
When bred separately, the plants always produced generation after generation. However, when lines with different phenotypes were crossed and only one of the parental phenotypes showed up in the offspring. However, when these hybrid plants were crossed, the offspring plants showed the two original phenotypes, in a characteristic 3:1 ratio, the more common phenotype being that of the parental hybrid plants. Mendel reasoned that each parent in the first cross was a homozygote for different alleles, that each contributed one allele to the offspring, with the result that all of these hybrids were heterozygotes, that one of the two alleles in the hybrid cross dominated expression of the other: A masked a; the final cross between two heterozygotes would produce AA, Aa, aa offspring in a 1:2:1 genotype ratio with the first two classes showing the phenotype, the last showing the phenotype, thereby producing the 3:1 phenotype ratio. Mendel did not use the terms gene, phenotype, genotype and heterozygote, all of which were introduced later.
He did introduce the notation of capital and lowercase letters for dominant and recessive alleles still in use today. Most animals and some plants have paired chromosomes, are described as diploid, they have two versions of each chromosome, one contributed by the mother's ovum, the other by the father's sperm, known as gametes, described as haploid, created through meiosis. These gametes fuse during fertilization during sexual reproduction, into a new single cell zygote, which divides multiple times, resulting in a new organism with the same number of pairs of chromosomes in each cell as its parents; each chromosome of a matching pair is structurally similar to the other, has a similar DNA sequence. The DNA in each chromosome functions as a series of discrete genes that influence various traits. Thus, each gene has a corresponding homologue, which may exist in different versions called alleles; the alleles at the same locus on the two homologous chromosomes may be different. The blood type of a human is determined by a gene that creates an A, B, AB or O blood type and is located in the long arm of chromosome nine.
There are three different alleles that could be present at this locus, but only two can be present in any individual, one inherited from their mother and one from their father. If two alleles of a given gene are identical, the organism is called a homozygote and is said to be homozygous with respect to that gene; the genetic makeup of an organism, either at a single locus or over all its genes collectively, is called its genotype. The genotype of an organism directly and indirectly affects its molecular and other traits, which individually or collectively are called its phenotype. At heterozygous gene loci, the two alleles interact to produce the phenotype. In complete dominance, the effect of one allele in a heterozygous genotype masks the effect of the other; the allele that mas
International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the
A chromosome is a deoxyribonucleic acid molecule with part or all of the genetic material of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle. Chromosomes are visible under a light microscope only when the cell is undergoing the metaphase of cell division. Before this happens, every chromosome is copied once, the copy is joined to the original by a centromere, resulting either in an X-shaped structure if the centromere is located in the middle of the chromosome or a two-arm structure if the centromere is located near one of the ends; the original chromosome and the copy are now called sister chromatids. During metaphase the X-shape structure is called a metaphase chromosome. In this condensed form chromosomes are easiest to distinguish and study. In animal cells, chromosomes reach their highest compaction level in anaphase during chromosome segregation.
Chromosomal recombination during meiosis and subsequent sexual reproduction play a significant role in genetic diversity. If these structures are manipulated incorrectly, through processes known as chromosomal instability and translocation, the cell may undergo mitotic catastrophe; this will make the cell initiate apoptosis leading to its own death, but sometimes mutations in the cell hamper this process and thus cause progression of cancer. Some use the term chromosome in a wider sense, to refer to the individualized portions of chromatin in cells, either visible or not under light microscopy. Others use the concept in a narrower sense, to refer to the individualized portions of chromatin during cell division, visible under light microscopy due to high condensation; the word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, introduced by Walther Flemming; some of the early karyological terms have become outdated.
For example and Chromosom, both ascribe color to a non-colored state. The German scientists Schleiden, Virchow and Bütschli were among the first scientists who recognized the structures now familiar as chromosomes. In a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity, it is the second of these principles, so original. Wilhelm Roux suggested. Boveri was able to confirm this hypothesis. Aided by the rediscovery at the start of the 1900s of Gregor Mendel's earlier work, Boveri was able to point out the connection between the rules of inheritance and the behaviour of the chromosomes. Boveri influenced two generations of American cytologists: Edmund Beecher Wilson, Nettie Stevens, Walter Sutton and Theophilus Painter were all influenced by Boveri. In his famous textbook The Cell in Development and Heredity, Wilson linked together the independent work of Boveri and Sutton by naming the chromosome theory of inheritance the Boveri–Sutton chromosome theory.
Ernst Mayr remarks that the theory was hotly contested by some famous geneticists: William Bateson, Wilhelm Johannsen, Richard Goldschmidt and T. H. Morgan, all of a rather dogmatic turn of mind. Complete proof came from chromosome maps in Morgan's own lab; the number of human chromosomes was published in 1923 by Theophilus Painter. By inspection through the microscope, he counted 24 pairs, his error was copied by others and it was not until 1956 that the true number, 46, was determined by Indonesia-born cytogeneticist Joe Hin Tjio. The prokaryotes – bacteria and archaea – have a single circular chromosome, but many variations exist; the chromosomes of most bacteria, which some authors prefer to call genophores, can range in size from only 130,000 base pairs in the endosymbiotic bacteria Candidatus Hodgkinia cicadicola and Candidatus Tremblaya princeps, to more than 14,000,000 base pairs in the soil-dwelling bacterium Sorangium cellulosum. Spirochaetes of the genus Borrelia are a notable exception to this arrangement, with bacteria such as Borrelia burgdorferi, the cause of Lyme disease, containing a single linear chromosome.
Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria have a one-point from which replication starts, whereas some archaea contain multiple replication origins; the genes in prokaryotes are organized in operons, do not contain introns, unlike eukaryotes. Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called the nucleoid; the nucleoid occupies a defined region of the bacterial cell. This structure is, dynamic and is maintained and remodeled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome. In archaea, the DNA in chromosomes is more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes. Certain bacteria contain plasmids or other extrachromosomal DNA; these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. In prokaryotes and viruses, the DNA is densely packed and organized.