Dominance (genetics)

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https://en.wikipedia.org/wiki/Dominance_(genetics) 

Autosomal dominant and autosomal recessive inheritance, the two most common Mendelian inheritance patterns. An autosome is any chromosome other than a sex chromosome.

In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second is called recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new (de novo) or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes (autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child (see Sex linkage). Since there is only one Y chromosome, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance, such as incomplete dominance, in which a gene variant has a partial effect compared to when it is present on both chromosomes, and co-dominance, in which different variants on each chromosome both show their associated traits.

Dominance is a key concept in Mendelian inheritance and classical genetics. Letters and Punnett squares are used to demonstrate the principles of dominance in teaching, and the upper-case letters are used to denote dominant alleles and lower-case letters are used for recessive alleles. An often quoted example of dominance is the inheritance of seed shape in peas. Peas may be round, associated with allele R, or wrinkled, associated with allele r. In this case, three combinations of alleles (genotypes) are possible: RR, Rr, and rr. The RR (homozygous) individuals have round peas, and the rr (homozygous) individuals have wrinkled peas. In Rr (heterozygous) individuals, the R allele masks the presence of the r allele, so these individuals also have round peas. Thus, allele R is dominant over allele r, and allele r is recessive to allele R.

Dominance is not inherent to an allele or its traits (phenotype). It is a strictly relative effect between two alleles of a given gene of any function; one allele can be dominant over a second allele of the same gene, recessive to a third, and co-dominant with a fourth. Additionally, one allele may be dominant for one trait but not others. Dominance differs from epistasis, the phenomenon of an allele of one gene masking the effect of alleles of a different gene.

Background

See also: Introduction to genetics

Inheritance of dwarfing in maize. Demonstrating the heights of plants from the two parent variations and their F1 heterozygous hybrid (centre)

Gregor Johann Mendel, "The Father of Genetics", promulgated the idea of dominance in the 1860s. However, it was not widely 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, and 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 the same phenotypes, generation after generation. However, when lines with different phenotypes were crossed (interbred), one and only one of the parental phenotypes showed up in the offspring (green, round, red, or tall). 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 (one parent AA and the other parent aa), that each contributed one allele to the offspring, with the result that all of these hybrids were heterozygotes (Aa), and that one of the two alleles in the hybrid cross dominated expression of the other: A masked a. The final cross between two heterozygotes (Aa X Aa) would produce AA, Aa, and aa offspring in a 1:2:1 genotype ratio with the first two classes showing the (A) phenotype, and the last showing the (a) phenotype, thereby producing the 3:1 phenotype ratio.

Mendel did not use the terms gene, allele, phenotype, genotype, homozygote, and heterozygote, all of which were introduced later. He did introduce the notation of capital and lowercase letters for dominant and recessive alleles, respectively, still in use today.

In 1928, British population geneticist Ronald Fisher proposed that dominance acted based on natural selection through the contribution of modifier genes. In 1929, American geneticist Sewall Wright responded by stating that dominance is simply a physiological consequence of metabolic pathways and the relative necessity of the gene involved.

Types of dominance

Complete dominance (Mendelian)

In complete dominance, the effect of one allele in a heterozygous genotype completely masks the effect of the other. The allele that masks are considered dominant to the other allele, and the masked allele is considered recessive.

When we only look at one trait determined by one pair of genes, we call it monohybrid inheritance. If the crossing is done between parents (P-generation, F0-generation) who are homozygote dominant and homozygote recessive, the offspring (F1-generation) will always have the heterozygote genotype and always present the phenotype associated with the dominant gene.

Monohybrid cross between heterozygotes (Gg), resulting in genotypical ratio 1:2:1 (GG:Gg:gg) and phenotypical ratio 3:1 (G:g).

However, if the F1-generation is further crossed with the F1-generation (heterozygote crossed with heterozygote) the offspring (F2-generation) will present the phenotype associated with the dominant gene ¾ times. Although heterozygote monohybrid crossing can result in two phenotype variants, it can result in three genotype variants -  homozygote dominant, heterozygote and homozygote recessive, respectively.

Dihybrid cross between heterozygotes (GgRr), resulting in the phenotypical ratio 9:3:3:1 (G and R: G and r: g and R: g and r)

In dihybrid inheritance we look at the inheritance of two pairs of genes simultaneous. Assuming here that the two pairs of genes are located at non-homologous chromosomes, such that they are not coupled genes (see genetic linkage) but instead inherited independently. Consider now the cross between parents (P-generation) of genotypes homozygote dominant and recessive, respectively. The offspring (F1-generation) will always heterozygous and present the phenotype associated with the dominant allele variant. However, when crossing the F1-generation there are four possible phenotypic possibilities and the phenotypical ratio for the F2-generation will always be 9:3:3:1.

Incomplete dominance (non-Mendelian)

This Punnett square illustrates incomplete dominance. In this example, the red petal trait associated with the R allele recombines with the white petal trait of the r allele. The plant incompletely expresses the dominant trait (R) causing plants with the Rr genotype to express flowers with less red pigment resulting in pink flowers. The colors are not blended together, the dominant trait is just expressed less strongly.

See also: partial dominance hypothesis

Incomplete dominance (also called partial dominance, semi-dominance, intermediate inheritance, or occasionally incorrectly co-dominance in reptile genetics) occurs when the phenotype of the heterozygous genotype is distinct from and often intermediate to the phenotypes of the homozygous genotypes. The phenotypic result often appears as a blended form of characteristics in the heterozygous state. For example, the snapdragon flower color is homozygous for either red or white. When the red homozygous flower is paired with the white homozygous flower, the result yields a pink snapdragon flower. The pink snapdragon is the result of incomplete dominance. A similar type of incomplete dominance is found in the four o'clock plant wherein pink color is produced when true-bred parents of white and red flowers are crossed. In quantitative genetics, where phenotypes are measured and treated numerically, if a heterozygote's phenotype is exactly between (numerically) that of the two homozygotes, the phenotype is said to exhibit no dominance at all, i.e. dominance exists only when the heterozygote's phenotype measure lies closer to one homozygote than the other.

When plants of the F₁ generation are self-pollinated, the phenotypic and genotypic ratio of the F₂ generation will be 1:2:1 (Red:Pink:White).

Co-dominance (non-Mendelian)

A and B blood types in humans show co-dominance, but the O type is recessive to A and B.

Co-dominance occurs when the contributions of both alleles are visible in the phenotype and neither allele masks another.

For example, in the ABO blood group system, chemical modifications to a glycoprotein (the H antigen) on the surfaces of blood cells are controlled by three alleles, two of which are co-dominant to each other (I^A, I^B) and dominant over the recessive i at the ABO locus. The I^A and I^B alleles produce different modifications. The enzyme coded for by I^A adds an N-acetylgalactosamine to a membrane-bound H antigen. The I^B enzyme adds a galactose. The i allele produces no modification. Thus the I^A and I^B alleles are each dominant to i (I^AI^A and I^Ai individuals both have type A blood, and I^BI^B and I^Bi individuals both have type B blood), but I^AI^B individuals have both modifications on their blood cells and thus have type AB blood, so the I^A and I^B alleles are said to be co-dominant.

Another example occurs at the locus for the beta-globin component of hemoglobin, where the three molecular phenotypes of Hb^A/Hb^A, Hb^A/Hb^S, and Hb^S/Hb^S are all distinguishable by protein electrophoresis. (The medical condition produced by the heterozygous genotype is called sickle-cell trait and is a milder condition distinguishable from sickle-cell anemia, thus the alleles show incomplete dominance concerning anemia, see above). For most gene loci at the molecular level, both alleles are expressed co-dominantly, because both are transcribed into RNA.

Co-dominance in a Punnett square. A white bull (WW) mates with a red cow (RR), and their offspring exhibit co-dominance expressing white and red hairs.

Co-dominance, where allelic products co-exist in the phenotype, is different from incomplete dominance, where the quantitative interaction of allele products produces an intermediate phenotype. For example, in co-dominance, a red homozygous flower and a white homozygous flower will produce offspring that have red and white spots. When plants of the F1 generation are self-pollinated, the phenotypic and genotypic ratio of the F2 generation will be 1:2:1 (Red:Spotted:White). These ratios are the same as those for incomplete dominance. Again, this classical terminology is inappropriate – in reality, such cases should not be said to exhibit dominance at all.

Relationship to other genetic concepts

Dominance can be influenced by various genetic interactions and it is essential to evaluate them when determining phenotypic outcomes. Multiple alleles, epistasis, pleiotropic genes, and polygenic characteristics are some factors that might influence the phenotypic outcome.

Multiple alleles

Main article: Allele § Multiple alleles

Although any individual of a diploid organism has at most two different alleles at a given locus, most genes exist in a large number of allelic versions in the population as a whole. This is called polymorphism, and is caused by mutations. Polymorphism can have an effect on the dominance relationship and phenotype, which is observed in the ABO blood group system. The gene responsible for human blood type have three alleles; A, B, and O, and their interactions result in different blood types based on the level of dominance the alleles expresses towards each other.

Epistasis

Main article: Epistasis

Epistasis is interactions between multiple alleles at different loci. More specifically, epistasis is when one gene can mask the phenotype of a gene at a completely different locus. Therefore, several genes can influence the phenotype expressed. Epistasis is slightly different from dominance in the fact that dominance is an allele-to-allele interaction at one locus while epistasis is a gene-to-gene interaction at different loci. The dominance relationship between alleles involved in epistatic interactions can influence the observed phenotypic ratios in offspring.

An example of epistasis can be seen in Labrador retriever coat colors. One gene at one locus codes for the color of hair but another gene at a different locus determines if the color is even deposited in the hair. Recessive epistasis is seen in this example due to recessive alleles for color desposition masking both the dominant black (B) allele and recessive brown (b) allele at the first locus to express a yellow coat in the Labrador retriever. The yellow color comes from no pigment being deposited in the hair shaft.

Other examples of epistasis interactions are dominant epistasis and duplicate recessive epistasis. Each type of epistasis is a modification of the dihyrbid ratio of 9:3:3:1.

Pleiotropic genes

Main article: Pleiotropy

Pleiotropic genes are genes where one single gene affects two or more characteristics. An example of this concept is Marfan Syndrome which is a mutation of the FBN1 gene. The effects this causes are a person's appearance being tall and long limbed. They can also have Scoliosis, Ectopia Lentis, and larger than normal aortas.  Pleiotropy shares a relationship with Epistasis. While pleiotropy represents one single gene, epistasis is multiple genes interacting with one another to cause different traits to arise.  it is helpful to recognize how Epistasis could affect viewing pleiotropic genes if different traits arise or mask themselves to varying degrees.

Polygenic characteristics

Main article: Polygene

Polygenic characteristics are those affected by multiple genes at different loci. These different genes interact in a way to produce a quantitative characteristic, which is a characteristic that presents a wide variety phenotypes, such as height in humans. The greater the number of genes that interact to influence this characteristic, the greater the number of different phenotypes possible due to more possible genotypes. Many more characteristics also appear to be affected by more than one gene located on different loci, including diabetes and some autoimmune diseases.

Mendelian inheritance

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Mendelian_inheritance

Gregor Mendel, the Moravian Augustinian friar who founded the modern science of genetics

Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later popularized by William Bateson. These principles were initially controversial. When Mendel's theories were integrated with the Boveri–Sutton chromosome theory of inheritance by Thomas Hunt Morgan in 1915, they became the core of classical genetics. Ronald Fisher combined these ideas with the theory of natural selection in his 1930 book The Genetical Theory of Natural Selection, putting evolution onto a mathematical footing and forming the basis for population genetics within the modern evolutionary synthesis.

History

Main article: History of genetics

The principles of Mendelian inheritance were named for and first derived by Gregor Johann Mendel, a nineteenth-century Moravian monk who formulated his ideas after conducting simple hybridization experiments with pea plants (Pisum sativum) he had planted in the garden of his monastery. Between 1856 and 1863, Mendel cultivated and tested some 5,000 pea plants. From these experiments, he induced two generalizations which later became known as Mendel's Principles of Heredity or Mendelian inheritance. He described his experiments in a two-part paper, Versuche über Pflanzen-Hybriden (Experiments on Plant Hybridization), that he presented to the Natural History Society of Brno on 8 February and 8 March 1865, and which was published in 1866.

Mendel's results were at first largely ignored. Although they were not completely unknown to biologists of the time, they were not seen as generally applicable, even by Mendel himself, who thought they only applied to certain categories of species or traits. A major roadblock to understanding their significance was the importance attached by 19th-century biologists to the apparent blending of many inherited traits in the overall appearance of the progeny,^{[citation needed]} now known to be due to multi-gene interactions, in contrast to the organ-specific binary characters studied by Mendel. In 1900, however, his work was "re-discovered" by three European scientists, Hugo de Vries, Carl Correns, and Erich von Tschermak. The exact nature of the "re-discovery" has been debated: De Vries published first on the subject, mentioning Mendel in a footnote, while Correns pointed out Mendel's priority after having read De Vries' paper and realizing that he himself did not have priority. De Vries may not have acknowledged truthfully how much of his knowledge of the laws came from his own work and how much came only after reading Mendel's paper. Later scholars have accused Von Tschermak of not truly understanding the results at all.

Regardless, the "re-discovery" made Mendelism an important but controversial theory. Its most vigorous promoter in Europe was William Bateson, who coined the terms "genetics" and "allele" to describe many of its tenets. The model of heredity was contested by other biologists because it implied that heredity was discontinuous, in opposition to the apparently continuous variation observable for many traits. Many biologists also dismissed the theory because they were not sure it would apply to all species. However, later work by biologists and statisticians such as Ronald Fisher showed that if multiple Mendelian factors were involved in the expression of an individual trait, they could produce the diverse results observed, thus demonstrating that Mendelian genetics is compatible with natural selection. Thomas Hunt Morgan and his assistants later integrated Mendel's theoretical model with the chromosome theory of inheritance, in which the chromosomes of cells were thought to hold the actual hereditary material, and created what is now known as classical genetics, a highly successful foundation which eventually cemented Mendel's place in history.

Mendel's findings allowed scientists such as Fisher and J.B.S. Haldane to predict the expression of traits on the basis of mathematical probabilities. An important aspect of Mendel's success can be traced to his decision to start his crosses only with plants he demonstrated were true-breeding. He only measured discrete (binary) characteristics, such as color, shape, and position of the seeds, rather than quantitatively variable characteristics. He expressed his results numerically and subjected them to statistical analysis. His method of data analysis and his large sample size gave credibility to his data. He had the foresight to follow several successive generations (P, F₁, F₂, F₃) of pea plants and record their variations. Finally, he performed "test crosses" (backcrossing descendants of the initial hybridization to the initial true-breeding lines) to reveal the presence and proportions of recessive characters.

Inheritance tools

Punnett squares

Punnett squares are a well known genetics tool that was created by an English geneticist, Reginald Punnett, which can visually demonstrate all the possible genotypes that an offspring can receive, given the genotypes of their parents. Each parent carries two alleles, which can be shown on the top and the side of the chart, and each contribute one of them towards reproduction at a time. Each of the squares in the middle demonstrates the number of times each pairing of parental alleles could combine to make potential offspring. Using probabilities, one can then determine which genotypes the parents can create, and at what frequencies they can be created.

For example, if two parents both have a heterozygous genotype, then there would be a 50% chance for their offspring to have the same genotype, and a 50% chance they would have a homozygous genotype. Since they could possibly contribute two identical alleles, the 50% would be halved to 25% to account for each type of homozygote, whether this was a homozygous dominant genotype, or a homozygous recessive genotype.

Pedigrees

Pedigrees are visual tree like representations that demonstrate exactly how alleles are being passed from past generations to future ones. They also provide a diagram displaying each individual that carries a desired allele, and exactly which side of inheritance it was received from, whether it was from their mother's side or their father's side. Pedigrees can also be used to aid researchers in determining the inheritance pattern for the desired allele, because they share information such as the gender of all individuals, the phenotype, a predicted genotype, the potential sources for the alleles, and also based its history, how it could continue to spread in the future generations to come. By using pedigrees, scientists have been able to find ways to control the flow of alleles over time, so that alleles that act problematic can be resolved upon discovery.

Mendel's genetic discoveries

Five parts of Mendel's discoveries were an important divergence from the common theories at the time and were the prerequisite for the establishment of his rules.

1. Characters are unitary, that is, they are discrete e.g.: purple vs. white, tall vs. dwarf. There is no medium-sized plant or light purple flower.
2. Genetic characteristics have alternate forms, each inherited from one of two parents. Today these are called alleles.
3. One allele is dominant over the other. The phenotype reflects the dominant allele.
4. Gametes are created by random segregation. Heterozygotic individuals produce gametes with an equal frequency of the two alleles.
5. Different traits have independent assortment. In modern terms, genes are unlinked.

According to customary terminology, the principles of inheritance discovered by Gregor Mendel are here referred to as Mendelian laws, although today's geneticists also speak of Mendelian rules or Mendelian principles, as there are many exceptions summarized under the collective term Non-Mendelian inheritance. The laws were initially formulated by the geneticist Thomas Hunt Morgan in 1916.

Characteristics Mendel used in his experiments

P-Generation and F₁-Generation: The dominant allele for purple-red flower hides the phenotypic effect of the recessive allele for white flowers. F₂-Generation: The recessive trait from the P-Generation phenotypically reappears in the individuals that are homozygous with the recessive genetic trait.

Myosotis: Colour and distribution of colours are inherited independently.

Mendel selected for the experiment the following characters of pea plants:

• Form of the ripe seeds (round or roundish, surface shallow or wrinkled)
• Colour of the seed–coat (white, gray, or brown, with or without violet spotting)
• Colour of the seeds and cotyledons (yellow or green)
• Flower colour (white or violet-red)
• Form of the ripe pods (simply inflated, not contracted, or constricted between the seeds and wrinkled)
• Colour of the unripe pods (yellow or green)
• Position of the flowers (axial or terminal)
• Length of the stem

When he crossed purebred white flower and purple flower pea plants (the parental or P generation) by artificial pollination, the resulting flower colour was not a blend. Rather than being a mix of the two, the offspring in the first generation (F₁-generation) were all purple-flowered. Therefore, he called this biological trait dominant. When he allowed self-fertilization in the uniform looking F₁-generation, he obtained both colours in the F₂ generation with a purple flower to white flower ratio of 3 : 1. In some of the other characters also one of the traits was dominant.

He then conceived the idea of heredity units, which he called hereditary "factors". Mendel found that there are alternative forms of factors—now called genes—that account for variations in inherited characteristics. For example, the gene for flower color in pea plants exists in two forms, one for purple and the other for white. The alternative "forms" are now called alleles. For each trait, an organism inherits two alleles, one from each parent. These alleles may be the same or different. An organism that has two identical alleles for a gene is said to be homozygous for that gene (and is called a homozygote). An organism that has two different alleles for a gene is said to be heterozygous for that gene (and is called a heterozygote).

Mendel hypothesized that allele pairs separate randomly, or segregate, from each other during the production of the gametes in the seed plant (egg cell) and the pollen plant (sperm). Because allele pairs separate during gamete production, a sperm or egg carries only one allele for each inherited trait. When sperm and egg unite at fertilization, each contributes its allele, restoring the paired condition in the offspring. Mendel also found that each pair of alleles segregates independently of the other pairs of alleles during gamete formation.

The genotype of an individual is made up of the many alleles it possesses. The phenotype is the result of the expression of all characteristics that are genetically determined by its alleles as well as by its environment. The presence of an allele does not mean that the trait will be expressed in the individual that possesses it. If the two alleles of an inherited pair differ (the heterozygous condition), then one determines the organism's appearance and is called the dominant allele; the other has no noticeable effect on the organism's appearance and is called the recessive allele.

Mendel's laws of inheritance

Mendel's laws of inheritance

Law	Definition
Law of dominance and uniformity	Some alleles are dominant while others are recessive; an organism with at least one dominant allele will display the effect of the dominant allele.
Law of segregation	During gamete formation, the alleles for each gene segregate from each other so that each gamete carries only one allele for each gene.
Law of independent assortment	Genes of different traits can segregate independently during the formation of gametes.

Law of dominance and uniformity

F₁ generation: All individuals have the same genotype and same phenotype expressing the dominant trait (red).
F₂ generation: The phenotypes in the second generation show a 3 : 1 ratio.
In the genotype 25 % are homozygous with the dominant trait, 50 % are heterozygous genetic carriers of the recessive trait, 25 % are homozygous with the recessive genetic trait and expressing the recessive character.

In Mirabilis jalapa and Antirrhinum majus are examples for intermediate inheritance.As seen in the F₁-generation, heterozygous plants have "light pink" flowers—a mix of "red" and "white". The F₂-generation shows a 1:2:1 ratio of red: light pink: white.

If two parents are mated with each other who differ in one genetic characteristic for which they are both homozygous (each pure-bred), all offspring in the first generation (F₁) are equal to the examined characteristic in genotype and phenotype showing the dominant trait. This uniformity rule or reciprocity rule applies to all individuals of the F₁-generation.

The principle of dominant inheritance discovered by Mendel states that in a heterozygote the dominant allele will cause the recessive allele to be "masked": that is, not expressed in the phenotype. Only if an individual is homozygous with respect to the recessive allele will the recessive trait be expressed. Therefore, a cross between a homozygous dominant and a homozygous recessive organism yields a heterozygous organism whose phenotype displays only the dominant trait.

The F₁ offspring of Mendel's pea crosses always looked like one of the two parental varieties. In this situation of "complete dominance", the dominant allele had the same phenotypic effect whether present in one or two copies.

But for some characteristics, the F₁ hybrids have an appearance in between the phenotypes of the two parental varieties. A cross between two four o'clock (Mirabilis jalapa) plants shows an exception to Mendel's principle, called incomplete dominance. Flowers of heterozygous plants have a phenotype somewhere between the two homozygous genotypes. In cases of intermediate inheritance (incomplete dominance) in the F₁-generation Mendel's principle of uniformity in genotype and phenotype applies as well. Research about intermediate inheritance was done by other scientists. The first was Carl Correns with his studies about Mirabilis jalapa.

Law of segregation of genes

A Punnett square for one of Mendel's pea plant experiments – self-fertilization of the F1 generation

The law of segregation of genes applies when two individuals, both heterozygous for a certain trait are crossed, for example, hybrids of the F₁-generation. The offspring in the F₂-generation differ in genotype and phenotype so that the characteristics of the grandparents (P-generation) regularly occur again. In a dominant-recessive inheritance, an average of 25% are homozygous with the dominant trait, 50% are heterozygous showing the dominant trait in the phenotype (genetic carriers), 25% are homozygous with the recessive trait and therefore express the recessive trait in the phenotype. The genotypic ratio is 1: 2 : 1, and the phenotypic ratio is 3: 1.

In the pea plant example, the capital "B" represents the dominant allele for purple blossom and lowercase "b" represents the recessive allele for white blossom. The pistil plant and the pollen plant are both F₁-hybrids with genotype "B b". Each has one allele for purple and one allele for white. In the offspring, in the F₂-plants in the Punnett-square, three combinations are possible. The genotypic ratio is 1 BB : 2 Bb : 1 bb. But the phenotypic ratio of plants with purple blossoms to those with white blossoms is 3 : 1 due to the dominance of the allele for purple. Plants with homozygous "b b" are white flowered like one of the grandparents in the P-generation.

In cases of incomplete dominance the same segregation of alleles takes place in the F₂-generation, but here also the phenotypes show a ratio of 1 : 2 : 1, as the heterozygous are different in phenotype from the homozygous because the genetic expression of one allele compensates the missing expression of the other allele only partially. This results in an intermediate inheritance which was later described by other scientists.

In some literature sources, the principle of segregation is cited as the "first law". Nevertheless, Mendel did his crossing experiments with heterozygous plants after obtaining these hybrids by crossing two purebred plants, discovering the principle of dominance and uniformity first.

Molecular proof of segregation of genes was subsequently found through observation of meiosis by two scientists independently, the German botanist Oscar Hertwig in 1876, and the Belgian zoologist Edouard Van Beneden in 1883. Most alleles are located in chromosomes in the cell nucleus. Paternal and maternal chromosomes get separated in meiosis because during spermatogenesis the chromosomes are segregated on the four sperm cells that arise from one mother sperm cell, and during oogenesis the chromosomes are distributed between the polar bodies and the egg cell. Every individual organism contains two alleles for each trait. They segregate (separate) during meiosis such that each gamete contains only one of the alleles. When the gametes unite in the zygote the alleles—one from the mother one from the father—get passed on to the offspring. An offspring thus receives a pair of alleles for a trait by inheriting homologous chromosomes from the parent organisms: one allele for each trait from each parent. Heterozygous individuals with the dominant trait in the phenotype are genetic carriers of the recessive trait.

Law of independent assortment

Segregation and independent assortment are consistent with the chromosome theory of inheritance.

Precondition for the example: Two parent dogs (P-generation) are homozygous for two different genetic traits. In each case one parent has the dominant, one the recessive allele. Their offsprings in the F₁-generation are heterozygous at both loci and show the dominant traits in their phenotypes according to the law of dominance and uniformity.
Now two heterozygous mature individuals of such F₁-generation are bred together. The dominant allele "E" (on the extension locus) provides black eumelanin in the coat. The recessive allele "e" (on the extension locus) hinders the storage of eumelanin in the coat, so only the pigments for the "Tan" colour are in the coat. The dominant allele S (on the S-locus) provides for the pigmentation of the entire coat. The recessive allele sP (on the S-locus) causes a white Piebald spotting. Now in the puppies in the F₂-generation all combinations are possible. The Piebald spotting and the genes for the different colour pigments are inherited independently of each other. Average number ratio of phenotypes 9:3:3:1.

For example 3 pairs of homologous chromosomes allow 8 possible combinations, all equally likely to move into the gamete during meiosis. This is the main reason for independent assortment. The equation to determine the number of possible combinations given the number of homologous pairs = 2^x (x = number of homologous pairs)

The law of independent assortment proposes alleles for separate traits are passed independently of one another. That is, the biological selection of an allele for one trait has nothing to do with the selection of an allele for any other trait. Mendel found support for this law in his dihybrid cross experiments. In his monohybrid crosses, an idealized 3:1 ratio between dominant and recessive phenotypes resulted. In dihybrid crosses, however, he found a 9:3:3:1 ratios. This shows that each of the two alleles is inherited independently from the other, with a 3:1 phenotypic ratio for each.

Independent assortment occurs in eukaryotic organisms during meiotic metaphase I, and produces a gamete with a mixture of the organism's chromosomes. The physical basis of the independent assortment of chromosomes is the random orientation of each bivalent chromosome along the metaphase plate with respect to the other bivalent chromosomes. Along with crossing over, independent assortment increases genetic diversity by producing novel genetic combinations.

There are many deviations from the principle of independent assortment due to genetic linkage.

Of the 46 chromosomes in a normal diploid human cell, half are maternally derived (from the mother's egg) and half are paternally derived (from the father's sperm). This occurs as sexual reproduction involves the fusion of two haploid gametes (the egg and sperm) to produce a zygote and a new organism, in which every cell has two sets of chromosomes (diploid). During gametogenesis the normal complement of 46 chromosomes needs to be halved to 23 to ensure that the resulting haploid gamete can join with another haploid gamete to produce a diploid organism.

In independent assortment, the chromosomes that result are randomly sorted from all possible maternal and paternal chromosomes. Because zygotes end up with a mix instead of a pre-defined "set" from either parent, chromosomes are therefore considered assorted independently. As such, the zygote can end up with any combination of paternal or maternal chromosomes. For human gametes, with 23 chromosomes, the number of possibilities is 2²³ or 8,388,608 possible combinations. This contributes to the genetic variability of progeny. Generally, the recombination of genes has important implications for many evolutionary processes.

Mendelian trait

A Mendelian trait is one whose inheritance follows Mendel's principles—namely, the trait depends only on a single locus, whose alleles are either dominant or recessive.

Many traits are inherited in a non-Mendelian fashion.

Non-Mendelian inheritance

Main article: Non-Mendelian inheritance

Mendel himself warned that care was needed in extrapolating his patterns to other organisms or traits. Indeed, many organisms have traits whose inheritance works differently from the principles he described; these traits are called non-Mendelian.

For example, Mendel focused on traits whose genes have only two alleles, such as "A" and "a". However, many genes have more than two alleles. He also focused on traits determined by a single gene. But some traits, such as height, depend on many genes rather than just one. Traits dependent on multiple genes are called polygenic traits.

Genetics of aging

 

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Genetics_of_aging

Many life span influencing genes affect the rate of DNA damage or DNA repair.

Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.

The first mutation found to increase longevity in an animal was the age-1 gene in Caenorhabditis elegans. Michael Klass discovered that lifespan of C. elegans could be altered by mutations, but Klass believed that the effect was due to reduced food consumption (calorie restriction). Thomas Johnson later showed that life extension of up to 65% was due to the mutation itself rather than due to calorie restriction, and he named the gene age-1 in the expectation that other genes that control aging would be found. The age-1 gene encodes the catalytic subunit of class-I phosphatidylinositol 3-kinase (PI3K).

A decade after Johnson's discovery daf-2, one of the two genes that are essential for dauer larva formation, was shown by Cynthia Kenyon to double C. elegans lifespan. Kenyon showed that the daf-2 mutants, which would form dauers above 25 °C (77 °F) would bypass the dauer state below 20 °C (68 °F) with a doubling of lifespan. Prior to Kenyon's study it was commonly believed that lifespan could only be increased at the cost of a loss of reproductive capacity, but Kenyon's nematodes maintained youthful reproductive capacity as well as extended youth in general. Subsequent genetic modification (PI3K-null mutation) to C. elegans was shown to extend maximum life span tenfold.

Long-lived mutants of C. elegans (age-1 and daf-2) were demonstrated to be resistant to oxidative stress and UV light. These long-lived mutants had a higher DNA repair capability than wild-type C. elegans. Knockdown of the nucleotide excision repair gene Xpa-1 increased sensitivity to UV and reduced the life span of the long-lived mutants. These findings support the hypothesis that DNA damage has a significant role in the aging process.

Genetic modifications in other species have not achieved as great a lifespan extension as have been seen for C. elegans. Drosophila melanogaster lifespan has been doubled. Genetic mutations in mice can increase maximum lifespan to 1.5 times normal, and up to 1.7 times normal when combined with calorie restriction.

In yeast, NAD+-dependent histone deacetylase Sir2 is required for genomic silencing at three loci: the yeast mating loci, the telomeres and the ribosomal DNA (rDNA). In some species of yeast, replicative aging may be partially caused by homologous recombination between rDNA repeats; excision of rDNA repeats results in the formation of extrachromosomal rDNA circles (ERCs). These ERCs replicate and preferentially segregate to the mother cell during cell division, and are believed to result in cellular senescence by titrating away (competing for) essential nuclear factors. ERCs have not been observed in other species (nor even all strains of the same yeast species) of yeast (which also display replicative senescence), and ERCs are not believed to contribute to aging in higher organisms such as humans (they have not been shown to accumulate in mammals in a similar manner to yeast). Extrachromosomal circular DNA (eccDNA) has been found in worms, flies, and humans. The origin and role of eccDNA in aging, if any, is unknown.

Despite the lack of a connection between circular DNA and aging in higher organisms, extra copies of Sir2 are capable of extending the lifespan of both worms and flies (though, in flies, this finding has not been replicated by other investigators, and the activator of Sir2 resveratrol does not reproducibly increase lifespan in either species.) Whether the Sir2 homologues in higher organisms have any role in lifespan is unclear, but the human SIRT1 protein has been demonstrated to deacetylate p53, Ku70, and the forkhead family of transcription factors. SIRT1 can also regulate acetylates such as CBP/p300, and has been shown to deacetylate specific histone residues.

RAS1 and RAS2 also affect aging in yeast and have a human homologue. RAS2 overexpression has been shown to extend lifespan in yeast.

Other genes regulate aging in yeast by increasing the resistance to oxidative stress. Superoxide dismutase, a protein that protects against the effects of mitochondrial free radicals, can extend yeast lifespan in stationary phase when overexpressed.

In higher organisms, aging is likely to be regulated in part through the insulin/IGF-1 pathway. Mutations that affect insulin-like signaling in worms, flies, and the growth hormone/IGF1 axis in mice are associated with extended lifespan. In yeast, Sir2 activity is regulated by the nicotinamidase PNC1. PNC1 is transcriptionally upregulated under stressful conditions such as caloric restriction, heat shock, and osmotic shock. By converting nicotinamide to niacin, nicotinamide is removed, inhibiting the activity of Sir2. A nicotinamidase found in humans, known as PBEF, may serve a similar function, and a secreted form of PBEF known as visfatin may help to regulate serum insulin levels. It is not known, however, whether these mechanisms also exist in humans, since there are obvious differences in biology between humans and model organisms.

Sir2 activity has been shown to increase under calorie restriction. Due to the lack of available glucose in the cells, more NAD+ is available and can activate Sir2. Resveratrol, a stilbenoid found in the skin of red grapes, was reported to extend the lifespan of yeast, worms, and flies (the lifespan extension in flies and worms have proved to be irreproducible by independent investigators). It has been shown to activate Sir2 and therefore mimics the effects of calorie restriction, if one accepts that caloric restriction is indeed dependent on Sir2.

According to the GenAge database of aging-related genes, there are over 1800 genes altering lifespan in model organisms: 838 in the soil roundworm (Caenorhabditis elegans), 883 in the bakers' yeast (Saccharomyces cerevisiae), 170 in the fruit fly (Drosophila melanogaster) and 126 in the mouse (Mus musculus).

"Healthspan, parental lifespan, and longevity are highly genetically correlated."

In July 2020 scientists, using public biological data on 1.75 m people with known lifespans overall, identify 10 genomic loci which appear to intrinsically influence healthspan, lifespan, and longevity – of which half have not been reported previously at genome-wide significance and most being associated with cardiovascular disease – and identify haem metabolism as a promising candidate for further research within the field. Their study suggests that high levels of iron in the blood likely reduce, and genes involved in metabolising iron likely increase healthy years of life in humans.

Ned Sharpless and collaborators demonstrated the first in vivo link between p16-expression and lifespan. They found reduced p16 expression in some tissues of mice with mutations that extend lifespan, as well as in mice that had their lifespan extended by food restriction. Jan van Deursen and Darren Baker in collaboration with Andre Terzic at the Mayo Clinic in Rochester, Minn., provided the first in vivo evidence for a causal link between cellular senescence and aging by preventing the accumulation of senescent cells in BubR1 progeroid mice. In the absence of senescent cells, the mice's tissues showed a major improvement in the usual burden of age-related disorders. They did not develop cataracts, avoided the usual wasting of muscle with age. They retained the fat layers in the skin that usually thin out with age and, in people, cause wrinkling. A second study led by Jan van Deursen in collaboration with a team of collaborators at the Mayo Clinic and Groningen University, provided the first direct in vivo evidence that cellular senescence causes signs of aging by eliminating senescent cells from progeroid mice by introducing a drug-inducible suicide gene and then treating the mice with the drug to kill senescent cells selectively, as opposed to decreasing whole body p16. Another Mayo study led by James Kirkland in collaboration with Scripps and other groups demonstrated that senolytics, drugs that target senescent cells, enhance cardiac function and improve vascular reactivity in old mice, alleviate gait disturbance caused by radiation in mice, and delay frailty, neurological dysfunction, and osteoporosis in progeroid mice. Discovery of senolytic drugs was based on a hypothesis-driven approach: the investigators leveraged the observation that senescent cells are resistant to apoptosis to discover that pro-survival pathways are up-regulated in these cells. They demonstrated that these survival pathways are the "Achilles heel" of senescent cells using RNA interference approaches, including Bcl-2-, AKT-, p21-, and tyrosine kinase-related pathways. They then used drugs known to target the identified pathways and showed these drugs kill senescent cells by apoptosis in culture and decrease senescent cell burden in multiple tissues in vivo. Importantly, these drugs had long term effects after a single dose, consistent with removal of senescent cells, rather than a temporary effect requiring continued presence of the drugs. This was the first study to show that clearing senescent cells enhances function in chronologically aged mice.

Genetically determined DNA repair capability and aging

The genetically determined capability to repair DNA damage appears to be a key aging factor in comparisons of several species of birds and animals. When the rate of accumulation of DNA damage (double-strand breaks) in the leukocytes of dolphins, goats, reindeer, American flamingos, and griffon vultures was compared to the longevity of individuals of these different species, it was found that the species with longer lifespans have slower accumulation of DNA damage. The activity of the enzyme PARP1, employed in several DNA repair process, was compared in thirteen different mammalian species and its activity was found to correlate with the maximum lifespan of the species. In humans, genetically determined DNA repair capability appears to influence lifespan. Lymphoblastoid cell lines established from blood samples of humans who lived past 100 years (centenarians) were found to have a significantly higher activity of the DNA repair protein Poly (ADP-ribose) polymerase (PARP) than cell lines from younger individuals (20 to 70 years old).

Herdles for increasing longevity

See also: Dysgenics and Genetic load § Deleterious mutation

Paternal age effect

A 2008 paper found a U-shaped association between paternal age and the overall mortality rate in children (i.e., mortality rate up to age 18). Although the relative mortality rates were higher, the absolute numbers were low, because of the relatively low occurrence of genetic abnormality. The study has been criticized for not adjusting for maternal health, which could have a large effect on child mortality. The researchers also found a correlation between paternal age and offspring death by injury or poisoning, indicating the need to control for social and behavioral confounding factors.

In 2012, a study showed that greater age at paternity tends to increase telomere length in offspring for up to two generations. Since telomere length affects health and mortality, this may affect the health and aging rate of the offspring. The authors speculated that this effect may provide a mechanism by which populations have some plasticity in adapting longevity to different social and ecological contexts.

Basic needs

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Basic_needs 

The basic needs approach is one of the major approaches to the measurement of absolute poverty in developing countries globally. It works to define the absolute minimum resources necessary for long-term physical well-being, usually in terms of consumption goods. The poverty line is then defined as the amount of income required to satisfy the needs of the people. The "basic needs" approach was introduced by the International Labour Organization's World Employment Conference in 1976. "Perhaps the high point of the WEP was the World Employment Conference of 1976, which proposed the satisfaction of basic human needs as the overriding objective of national and international development policy. The basic needs approach to development was endorsed by governments and workers' and employers' organizations from all over the world. It influenced the programmes and policies of major multilateral and bilateral development agencies, and was the precursor to the human development approach."

A traditional list of immediate "basic needs" is food (including water), shelter and clothing. Many modern lists emphasize the minimum level of consumption of "basic needs" of not just food, water, clothing and shelter, but also transportation (as proposed in the Third talk of Livelihood section of Three Principles of the People), sanitation, education, and healthcare. Different agencies use different lists.

The basic needs approach has been described as consumption-oriented, giving the impression "that poverty elimination is all too easy." Amartya Sen focused on 'capabilities' rather than consumption.

In the development discourse, the basic needs model focuses on the measurement of what is believed to be an eradicable level of poverty. Development programs following the basic needs approach do not invest in economically productive activities that will help a society carry its own weight in the future, rather they focus on ensuring each household meets its basic needs even if economic growth must be sacrificed today. These programs focus more on subsistence than fairness. Nevertheless, in terms of "measurement", the basic needs or absolute approach is important. The 1995 world summit on social development in Copenhagen had, as one of its principal declarations that all nations of the world should develop measures of both absolute and relative poverty and should gear national policies to "eradicate absolute poverty by a target date specified by each country in its national context."

Canada

Professor Chris Sarlo, an economist at Nipissing University in North Bay, Ontario, Canada and a senior fellow of the Fraser Institute, uses Statistics Canada's socio-economic databases, particularly the Survey of Household Spending to determine the cost of a list of household necessities. The list includes food, shelter, clothing, health care, personal care, essential furnishings, transportation and communication, laundry, home insurance, and miscellaneous; it assumes that education is provided freely to all residents of Canada. This is calculated for various communities across Canada and adjusted for family size. With this information, he determines the proportion of Canadian households that have insufficient income to afford those necessities. Based on his basic needs poverty threshold, the poverty rate in Canada, the poverty rate has declined from about 12% of Canadian households to about 5% since the 1970s. This is in sharp contrast to the results of Statistic Canada, Conference Board of Canada, the Organisation for Economic Co-operation and Development (OECD) and UNESCO reports using the relative poverty measure considered to the most useful for advanced industrial nations like Canada, which Sarlo rejects.

OECD and UNICEF rate Canada's poverty rate much higher using a relative poverty threshold. Statistics Canada's LICO, which Sarlo also rejects, also result in higher poverty rates. According to a 2008 report by the Organisation for Economic Co-operation and Development (OECD), the rate of poverty in Canada, is among the highest of the OECD member nations, the world's wealthiest industrialized nations. There is no official government definition and therefore, measure, for poverty in Canada. However, Dennis Raphael, author of Poverty in Canada: Implications for Health and Quality of Life reported that the United Nations Development Program (UNDP), the United Nations Children's Fund (UNICEF), the Organisation for Economic Co-operation and Development (OECD) and Canadian poverty researchers find that relative poverty is the "most useful measure for ascertaining poverty rates in wealthy developed nations such as Canada." In its report released the Conference Board.

United States

According to the US Department of Health and Human Services, an individual who makes $12,760 a year is considered below the poverty line. This amount is enough to cover living and transportation payments, bills, food, and clothing. In the United States, 13.1 percent of the population are reported to fall below the poverty level.

Government programs

SNAP

The Supplemental Nutrition Assistance Program, or SNAP, (formerly known as the Food Stamp Program) distributes food vouchers to households with incomes that fall within 130% of the federal poverty threshold. They support approximately 40 million people, including low income workers, unemployed citizens, and disabled heads of household. This program is an entitlement program, meaning if anyone is qualified, they will receive the benefits. The Food Stamp Program, the former name of SNAP, first began as a temporary program under President Roosevelt's (FDR) administration in 1939, allowing its recipients to buy surplus food determined by the Department. According to the US Department of Agriculture (USDA), the idea is credited to Henry Wallace, Secretary of Agriculture, and Milo Perkins, the program's first Administrator. After the program was discontinued from 1943 to 1961, the Food Stamp Program gradually expanded and became permanent during President Johnson's term in 1964. The program eventually grew nationwide, accepting more people and becoming more accessible. In the 1980s, the government addressed the extreme food insecurity in the US, leading to improvements like the sales tax elimination on food stamps. SNAP became eligible to the homeless and grew in resources, including nutrition education. 2013 marked their highest recipient rate, gradually decreasing to 42 million people in 2017. SNAP is the largest part of the government's Farm Bill, which is passed by Congress every five years. After much debate on funding, Congress passed the Farm Bill in 2018, portioning $664 billion to mainly SNAP. SNAP is proven to be highly beneficial to its participants, preventing a majority of households from reaching below the poverty line. Data from the USDA indicates that children who participate in SNAP are connected to more positive health effects and economic outcomes. 10% of SNAP recipients are reported to rise above the poverty line, and economic self-sufficiency especially increases for women. Furthermore, research by Mark Zandi has shown that a $1 increase in food stamp payments also increases GDP by $1.73.

The current benefits of SNAP, however, is threatened by proposals to cut funding and limit eligibility requirements. In the recent passing of the Farm Bill, there were attempts to limit eligibility and reduce benefits, which would affect about 2 million people. Ultimately, overall bipartisan support kept the total funding and prevented the proposals from being enacted. Along with this recent threat, there have been proposals to limit the programs in the past. In the mid-1990s, Congress imposed time limits for unemployed adults that were not disabled or raising children. In 2014, Republican representatives wanted to cut 5% of the program's funding, about $40 billion, for the next ten years. This did not pass, but funds were still cut by 1%, or $8.6 billion, creating limitations in the program. In 2017, the House of Representatives proposed to cut $150 billion from SNAP's funding through 2026. However, the cuts were not enacted, and the original budget amount remained. These past threats to the funding of SNAP imply an uncertain future for its ongoing benefits.

WIC

The Special Supplemental Nutrition Program for Women, Infants, and Children, best known as the WIC program, offers referrals to health care, nutrition information, and nutritious foods to low-income women, infants, and children who are at risk of health issues. Unlike SNAP, WIC is a federal grant program that runs under a specific amount of funds by the government, meaning not everyone who is qualified will receive benefits. WIC was first introduced in 1972 and became permanent in 1974. This program helps approximately 7.3 million participants each month and is reported to support 53% of infants born in the United States. In 2017, annual costs were $5.6 billion. Like SNAP, WIC is researched to also be highly effective for its participants. Benefits of WIC is associated with less premature and infant deaths and fewer occasions of low birthrates. Economically, $1.77 to $3.13 is saved in health care costs for each dollar invested in WIC.

HFFI

The Healthy Food Financing Initiative (HFFI) addresses place-based theories of poverty, aiming to develop grocery store chains in low-income communities and improve access to nutritious food. In the early 2000s, the metaphor of food deserts- low income communities that do not have access to grocery stores and nutritious foods- have been connected to health disparities. More than 29 million of US residents are reported to live in neighborhoods that resemble a food desert. The concept of the food desert has been increasingly linked to spatial reasons of poverty. It was understood that the food desert was the main reason why there were nutritional concerns in these neighborhoods. In 2010, President Obama introduced HFFI, which was passed by Congress in 2014 through the Farm Bill.

Criticisms of government programs

Criticism of SNAP

In the Oxford Academic journal, Social Work, Adriana Flores- a socialist advocate- brings attention to the limitations of government programs such as SNAP. Flores states that while the government assists people with food insecurity through SNAP, important basic needs like hygiene products are excluded, ultimately forcing low-income people to decide between hygiene items and other living payments. Flores considers SNAP as one of the few entitlement programs that need to be expanded.

Criticism of HFFI

In the International Journal of Urban and Regional Research, Laura Wolf-Powers criticizes HFFI, arguing that these policies imply that the origins of food insecurity mainly derive from geographical reasons. She and other scholars claim that income-centered policies would be significantly more effective. Wolf provides evidence that families with lower incomes have a larger tendency to live in food deserts. This makes them more prone to health issues and nutrition deprivation. Studies directly investigating shopping behavior of low-income residents disclose that their shopping decisions depend more on price, quality, staff, and similarities to other shoppers than simply the location of the store. The studies show that income is a more urgent reason than distance. Despite these studies and calls for reform, the journal illustrates the government's unwillingness to reform policies toward income redistribution and wage floors. The scholars notice optimistic changes in 2016, when 19 states established minimum wages, increasing economic self-sufficiency. This study seeks to criticize the government's spatial approach using investments and avoidance of income policies and labels the primary source of food insecurity as a lack of income.

Nongovernmental responses to basic needs insecurity

Food pantries on college campuses

Another project that started within the community is food pantries on college campuses. Food pantries were created to provide food at no cost and decrease food insecurity among students. In 2008, issues of food insecurity and homelessness among students were recognized by student affairs professionals due to the increasing tuition costs. A rising number of students especially in community colleges were experiencing food insecurity or homelessness, reaching between a fifth to two-thirds of American college students. This was more prevalent among Black and Latino communities, students in households that receive less than $20,000 in income, students with dependents, and former foster youth. They were reported to be skipping meals and purchasing cheaper foods, usually processed and unhealthy. These food pantries were founded by student leaders who advocated to improve food security and who also experienced food insecurity themselves. In the New Directions for Community Colleges, an academic journal, Jarrett Gupton observed food pantries and other solutions that benefited students. Because food pantries are limited due to the amount of food, staff, and hours of availability, Gupton suggests increasing students’ food literacy and utilizing community gardens, co-ops, and having affordable on-campus food plans. Although these nongovernmental approaches are beneficial to the public and spreading awareness of these basic needs issues, these projects are limited and cannot reach everyone in need. This issue leads to debates about government reforms and adopting a Rights-based approach to development to combat basic needs insecurity.