Chromosomal translocation
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. We can talk about balanced and unbalanced translocation, distinguish two main types: reciprocal-, Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Put, two broken off 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" together. A gene fusion may be created, it is detected on a karyotype of affected cells. Translocations can be unbalanced. Reciprocal translocations are an exchange of material between non-homologous chromosomes. Estimates of incidence range from about 1 in 500 to 1 in 625 human newborns; such translocations are harmless and may be found through prenatal diagnosis. However, carriers of balanced reciprocal translocations have increased risks of creating gametes with unbalanced chromosome translocations, leading to miscarriages or children with abnormalities.
Genetic counseling and genetic testing are offered to families that may carry a translocation. Most balanced translocation carriers are healthy and do not have any symptoms, but about 6% of them have a range of symptoms that may include autism, intellectual disability, or congenital anomalies. A gene disrupted or disregulated at the breakpoint of the translocation carrier is the cause of these symptoms, it is important to distinguish between chromosomal translocations occurring in gametogenesis, due to errors in meiosis, translocations that occur in cellular division of somatic cells, due to errors in mitosis. The former results in a chromosomal abnormality featured in all cells of the offspring, as in translocation carriers. Somatic translocations, on the other hand, result in abnormalities featured only in the affected cell line, as in chronic myelogenous leukemia with the Philadelphia chromosome translocation. Nonreciprocal translocation involves the transfer of genes from one chromosome to another nonhomologous chromosome.
Robertsonian translocation is a type of translocation caused by breaks at or near the centromeres of two acrocentric chromosomes. The reciprocal exchange of parts gives rise to one large metacentric chromosome and one small chromosome that may be lost from the organism with little effect because it contains so few genes; the resulting karyotype in humans leaves only 45 chromosomes, since two chromosomes have fused together. This has no direct effect on the phenotype, since the only genes on the short arms of acrocentrics are common to all of them and are present in variable copy number. Robertsonian translocations have been seen involving all combinations of acrocentric chromosomes; the most common translocation in humans involves chromosomes 13 and 14 and is seen in about 0.97 / 1000 newborns. Carriers of Robertsonian translocations are not associated with any phenotypic abnormalities, but there is a risk of unbalanced gametes that lead to miscarriages or abnormal offspring. For example, carriers of Robertsonian translocations involving chromosome 21 have a higher risk of having a child with Down syndrome.
This is known as a'translocation Downs'. This is due to a mis-segregation during gametogenesis; the mother has a higher risk of transmission than the father. Robertsonian translocations involving chromosome 14 carry a slight risk of uniparental disomy 14 due to trisomy rescue; some human diseases caused by translocations are: Cancer: Several forms of cancer are caused by acquired translocations. Translocations have been described in solid malignancies such as Ewing's sarcoma. Infertility: One of the would-be parents carries a balanced translocation, where the parent is asymptomatic but conceived fetuses are not viable. Down syndrome is caused in a minority of cases by a Robertsonian translocation of the chromosome 21 long arm onto the long arm of chromosome 14. Chromosomal translocations between the sex chromosomes can result in a number of genetic conditions, such as XX male syndrome: caused by a translocation of the SRY gene from the Y to the X chromosome The International System for Human Cytogenetic Nomenclature is used to denote a translocation between chromosomes.
The designation t is used to denote a translocation between chromosome A and chromosome B. The information in the second set of parentheses, when given, gives the precise location within the chromosome for chromosomes A and B respectively—with p indicating the short arm of the chromosome, q indicating the long arm, the numbers after p or q refers to regions and subbands seen when staining the chromosome with a staining dye. See the definition of a genetic locus; the translocation is the mechanism. In 1938, Karl Sax, at the Harvard University Biological Laboratories, published a paper entitled "Chromosome Aberrations Induced by X-rays", which demonstrated that radiation could induce major genetic changes by affecting chromosomal translocations; the paper is thought to mark the beginning of the field of radiation cytology, led him to be called "the father of radiation cytology". Accipitrida
Human
Humans are the only extant members of the subtribe Hominina. Together with chimpanzees and orangutans, they are part of the family Hominidae. A terrestrial animal, humans are characterized by their erect bipedal locomotion. Early hominins—particularly the australopithecines, whose brains and anatomy are in many ways more similar to ancestral non-human apes—are less referred to as "human" than hominins of the genus Homo. Several of these hominins used fire, occupied much of Eurasia, gave rise to anatomically modern Homo sapiens in Africa about 315,000 years ago. Humans began to exhibit evidence of behavioral modernity around 50,000 years ago, in several waves of migration, they ventured out of Africa and populated most of the world; the spread of the large and increasing population of humans has profoundly affected much of the biosphere and millions of species worldwide. Advantages that explain this evolutionary success include a larger brain with a well-developed neocortex, prefrontal cortex and temporal lobes, which enable advanced abstract reasoning, problem solving and culture through social learning.
Humans use tools better than any other animal. Humans uniquely use such systems of symbolic communication as language and art to express themselves and exchange ideas, organize themselves into purposeful groups. Humans create complex social structures composed of many cooperating and competing groups, from families and kinship networks to political states. Social interactions between humans have established an wide variety of values, social norms, rituals, which together undergird human society. Curiosity and the human desire to understand and influence the environment and to explain and manipulate phenomena have motivated humanity's development of science, mythology, religion and numerous other fields of knowledge. Though most of human existence has been sustained by hunting and gathering in band societies many human societies transitioned to sedentary agriculture some 10,000 years ago, domesticating plants and animals, thus enabling the growth of civilization; these human societies subsequently expanded, establishing various forms of government and culture around the world, unifying people within regions to form states and empires.
The rapid advancement of scientific and medical understanding in the 19th and 20th centuries permitted the development of fuel-driven technologies and increased lifespans, causing the human population to rise exponentially. The global human population was estimated to be near 7.7 billion in 2015. In common usage, the word "human" refers to the only extant species of the genus Homo—anatomically and behaviorally modern Homo sapiens. In scientific terms, the meanings of "hominid" and "hominin" have changed during the recent decades with advances in the discovery and study of the fossil ancestors of modern humans; the clear boundary between humans and apes has blurred, resulting in now acknowledging the hominids as encompassing multiple species, Homo and close relatives since the split from chimpanzees as the only hominins. There is a distinction between anatomically modern humans and Archaic Homo sapiens, the earliest fossil members of the species; the English adjective human is a Middle English loanword from Old French humain from Latin hūmānus, the adjective form of homō "man."
The word's use as a noun dates to the 16th century. The native English term man can refer to the species as well as to human males, or individuals of either sex; the species binomial "Homo sapiens" was coined by Carl Linnaeus in his 18th-century work Systema Naturae. The generic name "Homo" is a learned 18th-century derivation from Latin homō "man," "earthly being"; the species-name "sapiens" means "wise" or "sapient". Note that the Latin word homo refers to humans of either gender, that "sapiens" is the singular form; the genus Homo evolved and diverged from other hominins in Africa, after the human clade split from the chimpanzee lineage of the hominids branch of the primates. Modern humans, defined as the species Homo sapiens or to the single extant subspecies Homo sapiens sapiens, proceeded to colonize all the continents and larger islands, arriving in Eurasia 125,000–60,000 years ago, Australia around 40,000 years ago, the Americas around 15,000 years ago, remote islands such as Hawaii, Easter Island and New Zealand between the years 300 and 1280.
The closest living relatives of humans are gorillas. With the sequencing of the human and chimpanzee genomes, current estimates of similarity between human and chimpanzee DNA sequences range between 95% and 99%. By using the technique called a molecular clock which estimates the time required for the number of divergent mutations to accumulate between two lineages, the approximate date for the split between lineages can be calculated; the gibbons and orangutans were the first groups to split from the line leading to the h
Zygosity
Zygosity is the degree of similarity of the alleles for a trait in an organism. Most eukaryotes have two matching sets of chromosomes. Diploid organisms have the same loci on each of their two sets of homologous chromosomes except that the sequences at these loci may differ between the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a chromosomal sex-determination system. If both alleles of a diploid organism are the same, the organism is homozygous at that locus. If they are different, the organism is heterozygous at that locus. If one allele is missing, it is hemizygous; the DNA sequence of a gene varies from one individual to another. Those variations are called alleles. While some genes have only one allele because there is low variation, others have only one allele because deviation from that allele can be harmful or fatal, but most genes have two or more alleles. The frequency of different alleles varies throughout the population; some genes may have two alleles with equal distribution.
For other genes, one allele may be common, another allele may be rare. Sometimes, one allele is a disease-causing variation. Sometimes, the different variations in the alleles make no difference at all in the function of the organism. In diploid organisms, one allele is inherited from one from the female parent. Zygosity is a description of whether those two alleles have different DNA sequences. In some cases the term "zygosity" is used in the context of a single chromosome; the words homozygous and hemizygous are used to describe the genotype of a diploid organism at a single locus on the DNA. Homozygous describes a genotype consisting of two identical alleles at a given locus, heterozygous describes a genotype consisting of two different alleles at a locus, hemizygous describes a genotype consisting of only a single copy of a particular gene in an otherwise diploid organism, nullizygous refers to an otherwise-diploid organism in which both copies of the gene are missing. A cell is said to be homozygous for a particular gene when identical alleles of the gene are present on both homologous chromosomes.
The cell or organism in question is called a homozygote. True breeding organisms are always homozygous for the traits. An individual, homozygous-dominant for a particular trait carries two copies of the allele that codes for the dominant trait; this allele called the "dominant allele", is represented by a capital letter. When an organism is homozygous-dominant for a particular trait, the genotype is represented by a doubling of the symbol for that trait, such as "PP". An individual, homozygous-recessive for a particular trait carries two copies of the allele that codes for the recessive trait; this allele called the "recessive allele", is represented by the lowercase form of the letter used for the corresponding dominant trait. The genotype of an organism, homozygous-recessive for a particular trait is represented by a doubling of the appropriate letter, such as "pp". A diploid organism is heterozygous at a gene locus when its cells contain two different alleles of a gene; the cell or organism is called a heterozygote for the allele in question, therefore, heterozygosity refers to a specific genotype.
Heterozygous genotypes are represented by a capital letter and a lowercase letter, such as "Rr" or "Ss". Alternatively, a heterozygote for gene "R" is assumed to be "Rr"; the capital letter is written first. If the trait in question is determined by simple dominance, a heterozygote will express only the trait coded by the dominant allele, the trait coded by the recessive allele will not be present. In more complex dominance schemes the results of heterozygosity can be more complex. A heterozygous genotype can have a higher relative fitness than either the homozygous dominant or homozygous recessive genotype - this is called a heterozygote advantage. A chromosome in a diploid organism is hemizygous; the cell or organism is called a hemizygote. Hemizygosity is observed when one copy of a gene is deleted, or, in the heterogametic sex, when a gene is located on a sex chromosome. Hemizygosity must not be confused with haploinsufficiency, which describes a mechanism for producing a phenotype. For organisms in which the male is heterogametic, such as humans all X-linked genes are hemizygous in males with normal chromosomes, because they have only one X chromosome and few of the same genes are on the Y chromosome.
Transgenic mice generated through exogenous DNA microinjection of an embryo's pronucleus are considered to be hemizygous, because the introduced allele is expected to be incorporated into only one copy of any locus. A transgenic individual can be bred to homozygosity and maintained as an inbred line to reduce the need to confirm the genotype of each individual. In cultured mammalian cells, such as the Chinese hamster ovary cell line, a number of genetic loci are present in a functional hemizygous state, due to mutations or deletions in the other alleles. A nullizygous organism carries two mutant alleles for the same gene; the mutant alleles are both complete loss-of-function or'null' alleles, so homozygous null and n
Metaphase
Metaphase is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage. These chromosomes, carrying genetic information, align in the equator of the cell before being separated into each of the two daughter cells. Metaphase accounts for 4% of the cell cycle's duration. Preceded by events in prometaphase and followed by anaphase, microtubules formed in prophase have found and attached themselves to kinetochores in metaphase. In metaphase, the centromeres of the chromosomes convene themselves on the metaphase plate, an imaginary line, equidistant from the two centrosome poles; this alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochore microtubules, analogous to a tug-of-war between two people of equal strength, ending with the destruction of B cyclin. In certain types of cells, chromosomes do not line up at the metaphase plate and instead move back and forth between the poles randomly, only lining up along the middleline.
Early events of metaphase can coincide with the events of prometaphase, as chromosomes with connected kinetochores will start the events of metaphase individually before other chromosomes with unconnected kinetochores that are still lingering in the events of prometaphase. One of the cell cycle checkpoints occurs during metaphase. Only after all chromosomes have become aligned at the metaphase plate, when every kinetochore is properly attached to a bundle of microtubules, does the cell enter anaphase, it is thought that unattached or improperly attached kinetochores generate a signal to prevent premature progression to anaphase if most of the kinetochores have been attached and most of the chromosomes have been aligned. Such a signal creates the mitotic spindle checkpoint; this would be accomplished by regulation of the anaphase-promoting complex and separase. The analysis of metaphase chromosomes is one of the main tools of classical cytogenetics and cancer studies. Chromosomes are condensed and coiled in metaphase, which makes them most suitable for visual analysis.
Metaphase chromosomes make the classical picture of chromosomes. For classical cytogenetic analyses, cells are grown in short term culture and arrested in metaphase using mitotic inhibitor. Further they are used for slide preparation and banding of chromosomes to be visualised under microscope to study structure and number of chromosomes. Staining of the slides with Giemsa or Quinacrine, produces a pattern of in total up to several hundred bands. Normal metaphase spreads are used in methods like FISH and as a hybridization matrix for comparative genomic hybridization experiments. Malignant cells from solid tumors or leukemia samples can be used for cytogenetic analysis to generate metaphase preparations. Inspection of the stained metaphase chromosomes allows the determination of numerical and structural changes in the tumor cell genome, for example, losses of chromosomal segments or translocations, which may lead to chimeric oncogenes, such as bcr-abl in chronic myelogenous leukemia. Interphase Prophase Prometaphase Anaphase Telophase Media related to Metaphase at Wikimedia Commons
Genealogical DNA test
A genealogical DNA test is a DNA-based test which looks at specific locations of a person's genome, in order to find or verify ancestral genealogical relationships or to estimate the ethnic mixture of an individual. Since different testing companies use different ethnic reference groups, consisting of now living test persons with unknown pre-census time origins, the estimated ethnic mix is highly contradictory among companies. Genealogical DNA tests are not designed to give extensive information about medical conditions or diseases. Three principal types of genealogical DNA tests are available, with each looking at a different part of the genome and useful for different types of genealogical research: autosomal, Y-DNA. Autosomal tests may result in a large amount of DNA matches, along mixed male and female lines, each match with an estimated distance in the family tree. However, due to the random nature of which and how much DNA is inherited by each tested person from their common ancestors, secure conclusions can only be made a small number of generations back.
Autosomal tests are used in estimating ethnic mix. MtDNA and Y-DNA tests are much more reliable in finding prehistoric relationships to ancient DNA. However, they give fewer DNA matches, if any, that can be verified in family registers since they are limited to relationships along a strict female line and a strict male line respectively. MtDNA and Y-DNA tests are utilized to identify archeological cultures and migration paths of a person's ancestors along a strict mother's line or a strict father's line. Based on MtDNA and Y-DNA, a person's haplogroup can be identified. Only men can take Y-DNA tests; the first company to provide direct-to-consumer genetic DNA testing was the now defunct GeneTree. However, it did not offer multi-generational genealogy tests. In fall 2001, GeneTree sold its assets to Salt Lake City-based Sorenson Molecular Genealogy Foundation which originated in 1999. While in operation, SMGF provided free mitochondrial DNA tests to thousands. GeneTree returned to genetic testing for genealogy in conjunction with the Sorenson parent company and was part of the assets acquired in the Ancestry.com buyout of SMGF in 2012.
In 2000, Family Tree DNA, founded by Bennett Greenspan and Max Blankfeld, was the first company dedicated to direct-to-consumer testing for genealogy research. They offered eleven marker Y-Chromosome STR tests and HVR1 mitochondrial DNA tests, they tested in partnership with the University of Arizona. In 2007, 23andMe was the first company to offer a saliva-based direct-to-consumer genetic testing, it was the first to implement using autosomal DNA for ancestry testing, which all other major companies now use. In 2019 it was estimated that large genealogical testing companies had about 26 million DNA profiles. GEDmatch said half of their profiles were from the USA. A genealogical DNA test is performed on a DNA sample; this DNA sample can be obtained by a cheek-scraping, spit-cups and chewing gum. The sample collection uses a home test kit supplied by a service provider such as 23andMe, AncestryDNA, Family Tree DNA, or MyHeritage. After following the kit instructions on how to collect the sample, it is returned to the supplier for analysis.
There are three major types of genealogical DNA tests: Autosomal and X-DNA, Y-DNA and mtDNA. Autosomal tests look at chromosomes 1–22 and X; the autosomes are inherited from all recent ancestors. The X-chromosome follows a special inheritance pattern. Ethnicity estimates are included with this sort of testing. Y-DNA looks at the Y-chromosome, inherited father to son, so can only be taken by males to explore their direct paternal line. MtDNA looks at the mitochondria, inherited from mother to child and so can be used to explore one's direct maternal line. Y-DNA and mtDNA cannot be used for ethnicity estimates, but can be used to find one's haplogroup, unevenly distributed geographically. Direct-to-consumer DNA test companies have labeled haplogroups by continent or ethnicity, but these labels may be speculative or misleading. Autosomal DNA is contained in the 22 pairs of chromosomes not involved in determining a person's sex. Autosomal DNA recombines each generation, new offspring receive one set of chromosomes from each parent.
These are inherited equally from both parents and equally from grandparents to about 3x great-grand parents. Therefore, the number of markers inherited from a specific ancestor decreases by about half each generation. Inheritance is more unequal from more distant ancestors. A genealogical DNA test might test about 700,000 SNPs; the preparation of a report on the DNA in the sample proceeds in multiple stages: identification of the DNA base pair at specific SNP locations comparison with stored results interpretation of matches All major service providers use equipment with chips supplied by Illumina. The chip determines. Different versions of the chip are used by different service providers. In addition, updated versions of the Illumina chip may test different sets of SNP locations; the list of SNP locations
Chromosome 1
Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which are the basic units of information for DNA, it represents about 8% of the total DNA in human cells. It was the last completed chromosome, sequenced two decades after the beginning of the Human Genome Project; the following are some of the gene count estimates of human chromosome 1. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies. Among various projects, the collaborative consensus coding sequence project takes an conservative strategy. So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes; the following is a partial list of genes on human chromosome 1. For complete list, see the link in the infobox on the right. DENN1B hypothesized to be related to asthma Partial list of the genes located on p-arm of human chromosome 1: Partial list of the genes located on q-arm of human chromosome 1: There are 890 known diseases related to this chromosome.
Some of these diseases are hearing loss, Alzheimer's disease and breast cancer. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, in regions where no function is evident. Complete monosomy is invariably lethal before birth. Complete trisomy is lethal within days after conception; some partial deletions and partial duplications produce birth defects. The following diseases are some of those related to genes on chromosome 1: National Institutes of Health. "Chromosome 1". Genetics Home Reference. Retrieved 2017-05-06. "Final genome'chapter' published". BBC NEWS. 2006-05-18. Retrieved 2017-05-06. "Chromosome 1". Human Genome Project Information Archive 1990–2003. Retrieved 2017-05-06
Y chromosome
The Y chromosome is one of two sex chromosomes in mammals, including humans, many other animals. The other is the X chromosome. Y is the sex-determining chromosome in many species, since it is the presence or absence of Y that determines the male or female sex of offspring produced in sexual reproduction. In mammals, the Y chromosome contains the gene SRY; the DNA in the human Y chromosome is composed of about 59 million base pairs. The Y chromosome is passed only from father to son. With a 30% difference between humans and chimpanzees, the Y chromosome is one of the fastest-evolving parts of the human genome. To date, over 200 Y-linked genes have been identified. All Y-linked genes are expressed and hemizygous except in the cases of aneuploidy such as XYY syndrome or XXYY syndrome; the Y chromosome was identified as a sex-determining chromosome by Nettie Stevens at Bryn Mawr College in 1905 during a study of the mealworm Tenebrio molitor. Edmund Beecher Wilson independently discovered the same mechanisms the same year.
Stevens proposed that chromosomes always existed in pairs and that the Y chromosome was the pair of the X chromosome discovered in 1890 by Hermann Henking. She realized that the previous idea of Clarence Erwin McClung, that the X chromosome determines sex, was wrong and that sex determination is, in fact, due to the presence or absence of the Y chromosome. Stevens named the chromosome "Y" to follow on from Henking's "X" alphabetically; the idea that the Y chromosome was named after its similarity in appearance to the letter "Y" 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. Most therian mammals have only one pair of sex chromosomes in each cell. Males have one Y chromosome and one X chromosome. In mammals, the Y chromosome contains SRY, which triggers embryonic development as a male.
The Y chromosomes of humans and other mammals contain other genes needed for normal sperm production. There are exceptions, however. Among humans, some men have two Xs and a Y, or one X and two Ys, some women have three Xs or a single X instead of a double X. There are other exceptions in which SRY is damaged, or copied to the X. Many ectothermic vertebrates have no sex chromosomes. If they have different sexes, sex is determined environmentally rather than genetically. For some of them reptiles, sex depends on the incubation temperature; the X and Y chromosomes are thought to have evolved from a pair of identical chromosomes, termed autosomes, when an ancestral animal developed an allelic variation, a so-called "sex locus" – possessing this allele caused the organism to be male. The chromosome with this allele became the Y chromosome, while the other member of the pair became the X chromosome. Over time, genes that were beneficial for males and harmful to females either developed on the Y chromosome or were acquired through the process of translocation.
Until the X and Y chromosomes were thought to have diverged around 300 million years ago. However, research published in 2010, research published in 2008 documenting the sequencing of the platypus genome, has suggested that the XY sex-determination system would not have been present more than 166 million years ago, at the split of the monotremes from other mammals; this re-estimation of the age of the therian XY system is based on the finding that sequences that are on the X chromosomes of marsupials and eutherian mammals are present on the autosomes of platypus and birds. The older estimate was based on erroneous reports that the platypus X chromosomes contained these sequences. Recombination between the X and Y chromosomes proved harmful—it resulted in males without necessary genes found on the Y chromosome, females with unnecessary or harmful genes only found on the Y chromosome; as a result, genes beneficial to males accumulated near the sex-determining genes, recombination in this region was suppressed in order to preserve this male specific region.
Over time, the Y chromosome changed in such a way as to inhibit the areas around the sex determining genes from recombining at all with the X chromosome. As a result of this process, 95% of the human Y chromosome is unable to recombine. Only the tips of the Y and X chromosomes recombine; the tips of the Y chromosome that could recombine with the X chromosome are referred to as the pseudoautosomal region. The rest of the Y chromosome is passed on to the next generation intact, allowing for its use in tracking human evolution. By one estimate, the human Y chromosome has lost 1,393 of its 1,438 original genes over the course of its existence, linear extrapolation of this 1,393-gene loss over 300 million years gives a rate of genetic loss of 4.6 genes per million years. Continued loss of genes at the rate of 4.6 genes per million years would result in a Y chromosome with no functional genes –, the Y chromosome would lose complete function – within the next 10 million years, or half that time with the current age estimate of 160 million years.
Comparative genomic analysis reveals that many mammalian species are experiencing a similar loss of function in their h
