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Recessiveness of allele for protection of organism

Recessiveness of allele for protection of organism


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Heterozygous organisms profit from pairs of gene alleles. Harmful alleles when being recessive can be carried without any harm for the organism. Only when two harmful recessive alleles form a gene the negative effect is produced. As described in wiki article on allele:

A number of genetic disorders are caused when an individual inherits two recessive alleles for a single-gene trait. Recessive genetic disorders include Albinism, Cystic Fibrosis, Galactosemia, Phenylketonuria (PKU), and Tay-Sachs Disease. Other disorders are also due to recessive alleles, but because the gene locus is located on the X chromosome, so that males have only one copy (that is, they are hemizygous), they are more frequent in males than in females. Examples include red-green color blindness and Fragile X syndrome.

But some illnesses are carried by dominant alleles (from the same article):

Other disorders, such as Huntington disease, occur when an individual inherits only one dominant allele.

My questions are:

  1. How does harm from alleles correlate with their recessiveness? Generally speaking, do harmful alleles tend to be more recessive?
  2. How does benefits from alleles correlate with their dominance? Generally speaking, do "beneficial" alleles tend to be more dominant?

Instead of dividing mutations into two classes, dominant vs. recessive, consider categorizing them into classes based on how the mutation affects the gene--or the gene product. This yields loss-of-function (lf) alleles, that reduce the activity of the gene, or its product, and gain-of-function (gf) alleles that act as if they somehow increase the activity of the gene, or its product.

The logic underlying this classification was described in this classic reference: Muller, H. J. 1932. Further studies on the nature and causes of gene mutations. Proceedings of the 6th International Congress of Genetics, pp. 213-255. Since this was before DNA had been shown to be the genetic material his arguments are based solely on the phenotype of animals carrying various combinations of chromosomes. In particular he relies on genetic duplications and deficiencies (or deletions). In this nomenclature + indicates a chromosome carrying a wild-type (wt) allele of the gene, and m indicates a chromosome carrying a mutant allele of the gene. So if an +/m animal appears Wild-Type then that allele is recessive. Similarly, if an +/m animal has a Mutant phenotype then the allele is dominant.

There are two types of lf alleles:

  1. a hypomorph is a partial reduction in function and retains some residual gene function (e.g., a weak missense mutation, or a temperature-sensitive (ts) mutation. A hypomorph is recessive to a wt allele.

  2. an amorph is what we would call a true genetic and molecular null allele, a complete knockout of the gene, where there is no measurable function left (e.g., a nonsense mutation early in the protein coding region, or a small deletion that only removes a single gene). Amorphs are normally recessive to a wt allele (but see below for an exception)

There are three types of gf alleles:

  1. a hypermorph that elevates the level of the wt gene function (e.g., a promoter mutation that removes a negative regulatory site, leading to increased expression). Hypermorphs are dominant.

  2. an antimorph, or so-called dominant-negative (dn) allele that produces a mutant gene product that somehow interferes with the wt gene product (think poison product as one model). Antimorphs are always dominant over wt.

  3. a neomorph, an allele the results in a completely new gene function (e.g., if a glycolytic enzyme acquired sequence-specific DNA-binding activity, perhaps from a gene fusion event(?)). Neomorphic alleles are extremely rare and almost always dominant over wt.

So we have a straightforward mapping of lf alleles to recessive phenotypes, and gf alleles to dominant phenotypes. However there is an important exception to this simple scheme for genes that are dose-sensitive, or haploinsufficient. These are dominant lf alleles. For example, when halving the level of the gene product causes a mutant phenotype: +/null. Some well-known examples from the developmental genetics of model organisms are the Ubx gene, and the Notch gene from D. melanogaster.

Further discussion of these terms can also be found in Wikipedia


Harmful alleles can be both recessive or dominant. They do not tend to be more recessive or more dominant. But, you must look at it from a population genetics point of view. When a allele is dominant, it tends to be a highly selected for trait, an analogy of this would be black eyes are a dominant trait compared to blue eyes or green eyes, which is why you see so many people with black eyes in the world than blue.

So therefore dominant alleles are highly selected than recessive ones and when a dominant trait is harmful, the subject tends to get killed off or the line is destroyed in the process by the natural course of reproduction. What remains are recessive alleles which do not get a chance to attain recessiveness and are therefore carried forward by evolution as passenger, never expressing themselves until they get the chance to attain homozygous recessive state.


Incomplete Dominance

Figure 1. These pink flowers of a heterozygote snapdragon result from incomplete dominance. (credit: “storebukkebruse”/Flickr)

Mendel’s results, that traits are inherited as dominant and recessive pairs, contradicted the view at that time that offspring exhibited a blend of their parents’ traits. However, the heterozygote phenotype occasionally does appear to be intermediate between the two parents. For example, in the snapdragon, Antirrhinum majus (Figure 1), a cross between a homozygous parent with white flowers (C W C W) and a homozygous parent with red flowers (C R C R) will produce offspring with pink flowers (C R C W). (Note that different genotypic abbreviations are used for Mendelian extensions to distinguish these patterns from simple dominance and recessiveness.) This pattern of inheritance is described as incomplete dominance, denoting the expression of two contrasting alleles such that the individual displays an intermediate phenotype. The allele for red flowers is incompletely dominant over the allele for white flowers. However, the results of a heterozygote self-cross can still be predicted, just as with Mendelian dominant and recessive crosses. In this case, the genotypic ratio would be 1 C R C R:2 C R C W:1 C W C W, and the phenotypic ratio would be 1:2:1 for red:pink:white.

Incomplete dominance can be seen in several types of flowers, including pink tulips, carnations and roses—any pink flowers in these are due to the mixing of red and white alleles. Incomplete dominance can also be observed in some animals, such as rabbits. When a long-furred Angora breeds with a short-furred Rex, the offspring have medium-length fur. Tail length in dogs is similarly impacted by genes that display incomplete dominance patterns.


Contents

The concept of dominance was introduced by Gregor Johann Mendel. Though Mendel, "The Father of Genetics", first used the term in the 1860s, it was not 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, or round, or 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. Wright's explanation became an established fact in genetics, and the debate was largely ended. Some traits may have their dominance influenced by evolutionary mechanisms, however. [4] [5] [6]

Chromosomes, genes, and alleles Edit

Most animals and some plants have paired chromosomes, and are described as diploid. They have two versions of each chromosome, one contributed by the mother's ovum, and the other by the father's sperm, known as gametes, described as haploid, and created through meiosis. These gametes then fuse during fertilization during sexual reproduction, into a new single cell zygote, which divides multiple times, resulting in a new organism with the same number of pairs of chromosomes in each (non-gamete) cell as its parents.

Each chromosome of a matching (homologous) pair is structurally similar to the other, and has a very similar DNA sequence (loci, singular locus). The DNA in each chromosome functions as a series of discrete genes that influence various traits. Thus, each gene also has a corresponding homologue, which may exist in different versions called alleles. The alleles at the same locus on the two homologous chromosomes may be identical or different.

The blood type of a human is determined by a gene that creates an A, B, AB or O blood type and is located in the long arm of chromosome nine. There are three different alleles that could be present at this locus, but only two can be present in any individual, one inherited from their mother and one from their father. [7]

If two alleles of a given gene are identical, the organism is called a homozygote and is said to be homozygous with respect to that gene if instead the two alleles are different, the organism is a heterozygote and is heterozygous. The genetic makeup of an organism, either at a single locus or over all its genes collectively, is called its genotype. The genotype of an organism, directly and indirectly, affects its molecular, physical, and other traits, which individually or collectively are called its phenotype. At heterozygous gene loci, the two alleles interact to produce the phenotype.

Complete dominance Edit

In complete dominance, the effect of one allele in a heterozygous genotype completely masks the effect of the other. The allele that masks the other is said to be dominant to the latter, and the allele that is masked is said to be recessive to the former. [8] Complete dominance, therefore, means that the phenotype of the heterozygote is indistinguishable from that of the dominant homozygote.

A classic example of dominance is the inheritance of seed shape (pea 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 and rr are homozygous and Rr is heterozygous. The RR individuals have round peas and the rr individuals have wrinkled peas. In Rr individuals the R allele masks the presence of the r allele, so these individuals also have round peas. Thus, allele R is completely dominant to allele r, and allele r is recessive to allele R.

Incomplete dominance Edit

Incomplete dominance (also called partial dominance, semi-dominance or intermediate inheritance) occurs when the phenotype of the heterozygous genotype is distinct from and often intermediate to the phenotypes of the homozygous genotypes. 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). [9]

Co-dominance Edit

Co-dominance occurs when the contributions of both alleles are visible in the phenotype.

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 A I A and I A i individuals both have type A blood, and I B I B and I B i individuals both have type B blood), but I A I 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 with respect to 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, 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.

Addressing common misconceptions Edit

While it is often convenient to talk about a recessive allele or a dominant trait, dominance is not inherent to either an allele or its phenotype. Dominance is a relationship between two alleles of a gene and their associated phenotypes. A "dominant" allele is dominant to a particular allele of the same gene that can be inferred from the context, but it may be recessive to a third allele, and codominant to a fourth. Similarly, a "recessive" trait is a trait associated with a particular recessive allele implied by the context, but that same trait may occur in a different context where it is due to some other gene and a dominant allele.

Dominance is unrelated to the nature of the phenotype itself, that is, whether it is regarded as "normal" or "abnormal," "standard" or "nonstandard," "healthy" or "diseased," "stronger" or "weaker," or more or less extreme. A dominant or recessive allele may account for any of these trait types.

Dominance does not determine whether an allele is deleterious, neutral or advantageous. However, selection must operate on genes indirectly through phenotypes, and dominance affects the exposure of alleles in phenotypes, and hence the rate of change in allele frequencies under selection. Deleterious recessive alleles may persist in a population at low frequencies, with most copies carried in heterozygotes, at no cost to those individuals. These rare recessives are the basis for many hereditary genetic disorders.

Dominance is also unrelated to the distribution of alleles in the population. Both dominant and recessive alleles can be extremely common or extremely rare.

In genetics, symbols began as algebraic placeholders. When one allele is dominant to another, the oldest convention is to symbolize the dominant allele with a capital letter. The recessive allele is assigned the same letter in lower case. In the pea example, once the dominance relationship between the two alleles is known, it is possible to designate the dominant allele that produces a round shape by a capital-letter symbol R, and the recessive allele that produces a wrinkled shape by a lower-case symbol r. The homozygous dominant, heterozygous, and homozygous recessive genotypes are then written RR, Rr, and rr, respectively. It would also be possible to designate the two alleles as W and w, and the three genotypes WW, Ww, and ww, the first two of which produced round peas and the third wrinkled peas. The choice of "R" or "W" as the symbol for the dominant allele does not pre-judge whether the allele causing the "round" or "wrinkled" phenotype when homozygous is the dominant one.

A gene may have several alleles. Each allele is symbolized by the locus symbol followed by a unique superscript. In many species, the most common allele in the wild population is designated the wild type allele. It is symbolized with a + character as a superscript. Other alleles are dominant or recessive to the wild type allele. For recessive alleles, the locus symbol is in lower case letters. For alleles with any degree of dominance to the wild type allele, the first letter of the locus symbol is in upper case. For example, here are some of the alleles at the a locus of the laboratory mouse, Mus musculus: A y , dominant yellow a + , wild type and a bt , black and tan. The a bt allele is recessive to the wild type allele, and the A y allele is codominant to the wild type allele. The A y allele is also codominant to the a bt allele, but showing that relationship is beyond the limits of the rules for mouse genetic nomenclature.

Rules of genetic nomenclature have evolved as genetics has become more complex. Committees have standardized the rules for some species, but not for all. Rules for one species may differ somewhat from the rules for a different species. [10] [11]

Multiple alleles Edit

Although any individual of a diploid organism has at most two different alleles at any one locus (barring aneuploidies), most genes exist in a large number of allelic versions in the population as a whole. If the alleles have different effects on the phenotype, sometimes their dominance relationships can be described as a series.

For example, coat color in domestic cats is affected by a series of alleles of the TYR gene (which encodes the enzyme tyrosinase). The alleles C, c b , c s , and c a (full colour, Burmese, Siamese, and albino, respectively) produce different levels of pigment and hence different levels of colour dilution. The C allele (full colour) is completely dominant over the last three and the c a allele (albino) is completely recessive to the first three. [12] [13] [14]

Autosomal versus sex-linked dominance Edit

In humans and other mammal species, sex is determined by two sex chromosomes called the X chromosome and the Y chromosome. Human females are typically XX males are typically XY. The remaining pairs of chromosome are found in both sexes and are called autosomes genetic traits due to loci on these chromosomes are described as autosomal, and may be dominant or recessive. Genetic traits on the X and Y chromosomes are called sex-linked, because they are linked to sex chromosomes, not because they are characteristic of one sex or the other. In practice, the term almost always refers to X-linked traits and a great many such traits (such as red-green colour vision deficiency) are not affected by sex. Females have two copies of every gene locus found on the X chromosome, just as for the autosomes, and the same dominance relationships apply. Males, however, have only one copy of each X chromosome gene locus, and are described as hemizygous for these genes. The Y chromosome is much smaller than the X, and contains a much smaller set of genes, including, but not limited to, those that influence 'maleness', such as the SRY gene for testis determining factor. Dominance rules for sex-linked gene loci are determined by their behavior in the female: because the male has only one allele (except in the case of certain types of Y chromosome aneuploidy), that allele is always expressed regardless of whether it is dominant or recessive. Birds have opposite sex chromosomes: male birds have ZZ and female birds ZW chromosomes. However, inheritance of traits reminds XY-system otherwise male zebra finches may carry white colouring gene in their one of two Z chromosome, but females develop white colouring always. Grasshoppers have XO-system. Females have XX, but males only X. There is no Y chromosome at all.

Epistasis Edit

Epistasis ["epi + stasis = to sit on top"] is an interaction between alleles at two different gene loci that affect a single trait, which may sometimes resemble a dominance interaction between two different alleles at the same locus. Epistasis modifies the characteristic 9:3:3:1 ratio expected for two non-epistatic genes. For two loci, 14 classes of epistatic interactions are recognized. As an example of recessive epistasis, one gene locus may determine whether a flower pigment is yellow (AA or Aa) or green (aa), while another locus determines whether the pigment is produced (BB or Bb) or not (bb). In a bb plant, the flowers will be white, irrespective of the genotype of the other locus as AA, Aa, or aa. The bb combination is not dominant to the A allele: rather, the B gene shows recessive epistasis to the A gene, because the B locus when homozygous for the recessive allele (bb) suppresses phenotypic expression of the A locus. In a cross between two AaBb plants, this produces a characteristic 9:3:4 ratio, in this case of yellow : green : white flowers.

In dominant epistasis, one gene locus may determine yellow or green pigment as in the previous example: AA and Aa are yellow, and aa are green. A second locus determines whether a pigment precursor is produced (dd) or not (DD or Dd). Here, in a DD or Dd plant, the flowers will be colorless irrespective of the genotype at the A locus, because of the epistatic effect of the dominant D allele. Thus, in a cross between two AaDd plants, 3/4 of the plants will be colorless, and the yellow and green phenotypes are expressed only in dd plants. This produces a characteristic 12:3:1 ratio of white : yellow : green plants.

Supplementary epistasis occurs when two loci affect the same phenotype. For example, if pigment color is produced by CC or Cc but not cc, and by DD or Dd but not dd, then pigment is not produced in any genotypic combination with either cc or dd. That is, both loci must have at least one dominant allele to produce the phenotype. This produces a characteristic 9:7 ratio of pigmented to unpigmented plants. Complementary epistasis in contrast produces an unpigmented plant if and only if the genotype is cc and dd, and the characteristic ratio is 15:1 between pigmented and unpigmented plants. [15]

Classical genetics considered epistatic interactions between two genes at a time. It is now evident from molecular genetics that all gene loci are involved in complex interactions with many other genes (e.g., metabolic pathways may involve scores of genes), and that this creates epistatic interactions that are much more complex than the classic two-locus models.

Hardy–Weinberg principle (estimation of carrier frequency) Edit

The frequency of the heterozygous state (which is the carrier state for a recessive trait) can be estimated using the Hardy–Weinberg formula: p 2 + 2 p q + q 2 = 1 +2pq+q^<2>=1>

This formula applies to a gene with exactly two alleles and relates the frequencies of those alleles in a large population to the frequencies of their three genotypes in that population.

For example, if p is the frequency of allele A, and q is the frequency of allele a then the terms p 2 , 2pq, and q 2 are the frequencies of the genotypes AA, Aa and aa respectively. Since the gene has only two alleles, all alleles must be either A or a and p + q = 1 . Now, if A is completely dominant to a then the frequency of the carrier genotype Aa cannot be directly observed (since it has the same traits as the homozygous genotype AA), however it can be estimated from the frequency of the recessive trait in the population, since this is the same as that of the homozygous genotype aa. i.e. the individual allele frequencies can be estimated: q = √ f (aa) , p = 1 − q , and from those the frequency of the carrier genotype can be derived: f (Aa) = 2pq .

This formula relies on a number of assumptions and an accurate estimate of the frequency of the recessive trait. In general, any real-world situation will deviate from these assumptions to some degree, introducing corresponding inaccuracies into the estimate. If the recessive trait is rare, then it will be hard to estimate its frequency accurately, as a very large sample size will be needed.

Dominant versus advantageous Edit

The property of "dominant" is sometimes confused with the concept of advantageous and the property of "recessive" is sometimes confused with the concept of deleterious, but the phenomena are distinct. Dominance describes the phenotype of heterozygotes with regard to the phenotypes of the homozygotes and without respect to the degree to which different phenotypes may be beneficial or deleterious. Since many genetic disease alleles are recessive and because the word dominance has a positive connotation, the assumption that the dominant phenotype is superior with respect to fitness is often made. This is not assured however as discussed below while most genetic disease alleles are deleterious and recessive, not all genetic diseases are recessive.

Nevertheless, this confusion has been pervasive throughout the history of genetics and persists to this day. Addressing this confusion was one of the prime motivations for the publication of the Hardy–Weinberg principle.

The molecular basis of dominance was unknown to Mendel. It is now understood that a gene locus includes a long series (hundreds to thousands) of bases or nucleotides of deoxyribonucleic acid (DNA) at a particular point on a chromosome. The central dogma of molecular biology states that "DNA makes RNA makes protein", that is, that DNA is transcribed to make an RNA copy, and RNA is translated to make a protein. In this process, different alleles at a locus may or may not be transcribed, and if transcribed may be translated to slightly different versions of the same protein (called isoforms). Proteins often function as enzymes that catalyze chemical reactions in the cell, which directly or indirectly produce phenotypes. In any diploid organism, the DNA sequences of the two alleles present at any gene locus may be identical (homozygous) or different (heterozygous). Even if the gene locus is heterozygous at the level of the DNA sequence, the proteins made by each allele may be identical. In the absence of any difference between the protein products, neither allele can be said to be dominant (see co-dominance, above). Even if the two protein products are slightly different (allozymes), it is likely that they produce the same phenotype with respect to enzyme action, and again neither allele can be said to be dominant.

Loss of function and haplosufficiency Edit

Dominance typically occurs when one of the two alleles is non-functional at the molecular level, that is, it is not transcribed or else does not produce a functional protein product. This can be the result of a mutation that alters the DNA sequence of the allele. [ citation needed ] An organism homozygous for the non-functional allele will generally show a distinctive phenotype, due to the absence of the protein product. For example, in humans and other organisms, the unpigmented skin of the albino phenotype [16] results when an individual is homozygous for an allele that encodes a non-functional version of an enzyme needed to produce the skin pigment melanin. It is important to understand that it is not the lack of function that allows the allele to be described as recessive: this is the interaction with the alternative allele in the heterozygote. Three general types of interaction are possible:

  1. In the typical case, the single functional allele makes sufficient protein to produce a phenotype identical to that of the homozygote: this is called haplosufficiency. For example, suppose the standard amount of enzyme produced in the functional homozygote is 100%, with the two functional alleles contributing 50% each. The single functional allele in the heterozygote produces 50% of the standard amount of enzyme, which is sufficient to produce the standard phenotype. If the heterozygote and the functional-allele homozygote have identical phenotypes, the functional allele is dominant to the non-functional allele. This occurs at the albino gene locus: the heterozygote produces sufficient enzyme to convert the pigment precursor to melanin, and the individual has standard pigmentation.
  2. Less commonly, the presence of a single functional allele gives a phenotype that is not normal but less severe than that of the non-functional homozygote. This occurs when the functional allele is not haplo-sufficient. The terms haplo-insufficiency and incomplete dominance are typically applied to these cases. The intermediate interaction occurs where the heterozygous genotype produces a phenotype intermediate between the two homozygotes. Depending on which of the two homozygotes the heterozygote most resembles, one allele is said to show incomplete dominance over the other. For example, in humans the Hb gene locus is responsible for the Beta-chain protein (HBB) that is one of the two globin proteins that make up the blood pigment hemoglobin. [16] Many people are homozygous for an allele called Hb A some persons carry an alternative allele called Hb S , either as homozygotes or heterozygotes. The hemoglobin molecules of Hb S /Hb S homozygotes undergo a change in shape that distorts the morphology of the red blood cells, and causes a severe, life-threatening form of anemia called sickle-cell anemia. Persons heterozygous Hb A /Hb S for this allele have a much less severe form of anemia called sickle-cell trait. Because the disease phenotype of Hb A /Hb S heterozygotes is more similar to but not identical to the Hb A /Hb A homozygote, the Hb A allele is said to be incompletely dominant to the Hb S allele.
  3. Rarely, a single functional allele in the heterozygote may produce insufficient gene product for any function of the gene, and the phenotype resembles that of the homozygote for the non-functional allele. This complete haploinsufficiency is very unusual. In these cases, the non-functional allele would be said to be dominant to the functional allele. This situation may occur when the non-functional allele produces a defective protein that interferes with the proper function of the protein produced by the standard allele. The presence of the defective protein "dominates" the standard protein, and the disease phenotype of the heterozygote more closely resembles that of the homozygote for two defective alleles. The term "dominant" is often incorrectly applied to defective alleles whose homozygous phenotype has not been examined, but which cause a distinct phenotype when heterozygous with the normal allele. This phenomenon occurs in a number of trinucleotide repeat diseases, one example being Huntington's disease. [17]

Dominant-negative mutations Edit

Many proteins are normally active in the form of a multimer, an aggregate of multiple copies of the same protein, otherwise known as a homomultimeric protein or homooligomeric protein. In fact, a majority of the 83,000 different enzymes from 9800 different organisms in the BRENDA Enzyme Database [18] represent homooligomers. [19] When the wild-type version of the protein is present along with a mutant version, a mixed multimer can be formed. A mutation that leads to a mutant protein that disrupts the activity of the wild-type protein in the multimer is a dominant-negative mutation.

A dominant-negative mutation may arise in a human somatic cell and provide a proliferative advantage to the mutant cell, leading to its clonal expansion. For instance, a dominant-negative mutation in a gene necessary for the normal process of programmed cell death (Apoptosis) in response to DNA damage can make the cell resistant to apoptosis. This will allow proliferation of the clone even when excessive DNA damage is present. Such dominant-negative mutations occur in the tumor suppressor gene p53. [20] [21] The P53 wild-type protein is normally present as a four-protein multimer (oligotetramer). Dominant-negative p53 mutations occur in a number of different types of cancer and pre-cancerous lesions (e.g. brain tumors, breast cancer, oral pre-cancerous lesions and oral cancer). [20]

Dominant-negative mutations also occur in other tumor suppressor genes. For instance two dominant-negative germ line mutations were identified in the Ataxia telangiectasia mutated (ATM) gene which increases susceptibility to breast cancer. [22] Dominant negative mutations of the transcription factor C/EBPα can cause acute myeloid leukemia. [23] Inherited dominant negative mutations can also increase the risk of diseases other than cancer. Dominant-negative mutations in Peroxisome proliferator-activated receptor gamma (PPARγ) are associated with severe insulin resistance, diabetes mellitus and hypertension. [24]

Dominant-negative mutations have also been described in organisms other than humans. In fact, the first study reporting a mutant protein inhibiting the normal function of a wild-type protein in a mixed multimer was with the bacteriophage T4 tail fiber protein GP37. [25] Mutations that produce a truncated protein rather than a full-length mutant protein seem to have the strongest dominant-negative effect in the studies of P53, ATM, C/EBPα, and bacteriophage T4 GP37.

In humans, many genetic traits or diseases are classified simply as "dominant" or "recessive". Especially with so-called recessive diseases, which are indeed a factor of recessive genes, but can oversimplify the underlying molecular basis and lead to misunderstanding of the nature of dominance. For example, the recessive genetic disease phenylketonuria (PKU) [26] results from any of a large number (>60) of alleles at the gene locus for the enzyme phenylalanine hydroxylase (PAH). [27] Many of these alleles produce little or no PAH, as a result of which the substrate phenylalanine (Phe) and its metabolic byproducts accumulate in the central nervous system and can cause severe intellectual disability if untreated.

To illustrate these nuances, the genotypes and phenotypic consequences of interactions among three hypothetical PAH alleles are shown in the following table: [28]

In unaffected persons homozygous for a standard functional allele (AA), PAH activity is standard (100%), and the concentration of phenylalanine in the blood [Phe] is about 60 μM (= μmol/L). In untreated persons homozygous for one of the PKU alleles (BB), PAH activity is close to zero, [Phe] ten to forty times standard, and the individual manifests PKU.

In the AB heterozygote, PAH activity is only 30% (not 50%) of standard, blood [Phe] is elevated two-fold, and the person does not manifest PKU. Thus, the A allele is dominant to the B allele with respect to PKU, but the B allele is incompletely dominant to the A allele with respect to its molecular effect, determination of PAH activity level (0.3% < 30% << 100%). Finally, the A allele is an incomplete dominant to B with respect to [Phe], as 60 μM < 120 μM << 600 μM. Note once more that it is irrelevant to the question of dominance that the recessive allele produces a more extreme [Phe] phenotype.

For a third allele C, a CC homozygote produces a very small amount of PAH enzyme, which results in a somewhat elevated level of [Phe] in the blood, a condition called hyperphenylalaninemia, which does not result in intellectual disability.

That is, the dominance relationships of any two alleles may vary according to which aspect of the phenotype is under consideration. It is typically more useful to talk about the phenotypic consequences of the allelic interactions involved in any genotype, rather than to try to force them into dominant and recessive categories.


Principles of Heredity Key

1. Gregor _____ Mendel __________, the "father of genetics"
2. The first _____ filial _____ generation is the offspring of a cross between parents that are pure for a given trait.
3. The principle of _ dominance _______ and recessiveness.
4. The outward expression or appearance: _____ phenotype _________
5. Cross that involves parents that differ in TWO traits. __ dihybrid ___
6. The study of heredity: _____ genetics ____________
7. An alternate form of a gene: ____ allele __________
8. The Principle of _____ independent ____________ Assortment
9. Having non identical alleles (not pure ex. Aa): __ heterozygous ___
10. Having identical alleles (pure, ex. AA): _ homozygous _________
11. Square used to determine probability and results of cross: punnett
12. The allele that is masked or covered up by the dominant allele: ___ recessive ___________
13. The genetic make-up or an organism (Tt): ____ genotype _______________
14. A cross that involves ONE pair of contrasting traits: ____ monohybrid _____________
15. The plants Mendel did his studies on: ______ pea _______
16. The likelihood that an event will happen: _________ probability _____________
17. When neither allele is dominant (they are both expressed) ______ codominant ___________
18. Principle of _____ segregation _______ states that alleles separate when gametes are formed.


Q: Use your knowledge of Cell &amp Molecular Biology to design solutions for treating COVID-19 based.

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Q: During a transfer of liquids using a micropipette: what would you and/or your professor consider an .

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Q: What kind of diseases are studied using genome-wide association studies? a. viral diseases b. single.

A: Genome-wide association studies are used in genetic research in order to associate specific genetic .

Q: Name four features that together contribute to our uniqueness and define us as human.

A: The group of multicellular and heterotrophic organisms belonging to the kingdom Animalia is called a.

Q: A) Outline the experimental procedure for cloning a eukaryotic gene and expressing it in E. coli. Fo.

A: Genetic engineering has enabled us to engineer the genes according to the desired gene product. It i.

Q: The introduction of genes into plants is a common practice that has generated not only a host of gen.

A: No, the tumor-inducing genes are removed from the plasmid, eliminating the threat of tumor productio.

Q: Explain The Fibrinolytic System?

A: Blood clotting also called coagulation, is a process to prevent excessive bleeding when there is an .

Q: Which of the following is not an essentialpart of anatomical position?a. feet togetherb. feet flat o.

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Incomplete Dominance

Mendel’s results, that traits are inherited as dominant and recessive pairs, contradicted the view at that time that offspring exhibited a blend of their parents’ traits. However, the heterozygote phenotype occasionally does appear to be intermediate between the two parents. For example, in the snapdragon, Antirrhinum majus (Figure), a cross between a homozygous parent with white flowers (C W C W ) and a homozygous parent with red flowers (C R C R ) will produce offspring with pink flowers (C R C W ). (Note that different genotypic abbreviations are used for Mendelian extensions to distinguish these patterns from simple dominance and recessiveness.) This pattern of inheritance is described as incomplete dominance , denoting the expression of two contrasting alleles such that the individual displays an intermediate phenotype. The allele for red flowers is incompletely dominant over the allele for white flowers. However, the results of a heterozygote self-cross can still be predicted, just as with Mendelian dominant and recessive crosses. In this case, the genotypic ratio would be 1 C R C R :2 C R C W :1 C W C W , and the phenotypic ratio would be 1:2:1 for red:pink:white.

These pink flowers of a heterozygote snapdragon result from incomplete dominance. (credit: “storebukkebruse”/Flickr)


Modifying Mendel

Although Mendel's studies established most of the important general principles of inheritance, some important extensions of his laws have since been discovered. The discovery of chromosomes led to an important exception to Mendel's laws. Mendel assumed that any two pairs of traits would sort independently. However, two traits carried on the same chromosome cannot separate as freely as two traits carried on different chromosomes, thus limiting the Law of Independent Assortment. Traits carried on the same chromosome are said to be linked. If the chromosomal locations (loci) for the two traits are very close together, a particular pair of alleles (for example, purple flowers and thick stems) is likely to remain together. If the loci are far apart, the two alleles may become separated during the crossing over phase of meiosis. In that case, Mendel's assortment law will be more likely to hold. The frequency with which a particular pair of alleles on a chromosome is separated during meiosis can be used to determine their distance apart, and is a first step in mapping chromosomes.

The simple Mendelian concepts of dominance and recessiveness have also undergone important refinements and extensions. In many cases, recessiveness is known to be due to a mutation that makes the genes or resulting protein nonfunctional. Presence of one functional allele is often enough to produce adequate levels of protein, and so the functional allele has a dominant effect on the phenotype of the organism. Only when both alleles are defective does the recessive phenotype appear. In some cases, a gene will become mutated to take on a new, harmful function. Such "toxic gain-of-function" mutations are often dominant.

In the case of all of the pairs of allelic genes studied by Mendel, one of the two alleles was completely dominant to the other. However, it is more often the case that an organism with two different alleles of a gene will exhibit characteristics that are intermediate between those determined by either allele separately. For example, the progeny of a cross between red-flowered and white-flowered snapdragons have pink flowers. This type of interaction between alleles is called incomplete dominance. In a related phenomenon, co-dominance, both alleles present affect the phenotype.

The discovery around 1950 that genes are made of deoxyribonucleic acid (DNA), and the elucidation of the structure of DNA in 1953 by James Watson and Francis Crick, led to a virtual explosion of scientific and technical advances in the analysis and manipulation of the genetic material. Thanks to these developments, Mendelian analysis has been largely replaced by techniques in which the analysis is carried out at the cellular and molecular level. Individual genes can simply be identified, isolated, and copied, and their precise molecular structure and function can usually be determined. An example of this type of analysis is represented in the Human Genome Project, in which the structure of all of the genes in human chromosomes is being elucidated. The origins of all of this sophisticated technology, however, can be traced back to the nineteenth-century pioneering methodical studies on inheritance in peas by Gregor Mendel.


Alleles Can Be Dominant or Recessive

Most familiar animals and some plants have paired chromosomes and are described as diploid. They have two versions of each chromosome: one contributed by the female parent in her ovum and one by the male parent in his sperm. These are joined at fertilization. The ovum and sperm cells (the gametes) have only one copy of each chromosome and are described as haploid.

Figure (PageIndex<1>): Recessive traits are only visible if an individual inherits two copies of the recessive allele: The child in the photo expresses albinism, a recessive trait.

Mendel&rsquos law of dominance states that in a heterozygote, one trait will conceal the presence of another trait for the same characteristic. Rather than both alleles contributing to a phenotype, the dominant allele will be expressed exclusively. The recessive allele will remain &ldquolatent,&rdquo but will be transmitted to offspring by the same manner in which the dominant allele is transmitted. The recessive trait will only be expressed by offspring that have two copies of this allele these offspring will breed true when self-crossed.

By definition, the terms dominant and recessive refer to the genotypic interaction of alleles in producing the phenotype of the heterozygote. The key concept is genetic: which of the two alleles present in the heterozygote is expressed, such that the organism is phenotypically identical to one of the two homozygotes. It is sometimes convenient to talk about the trait corresponding to the dominant allele as the dominant trait and the trait corresponding to the hidden allele as the recessive trait. However, this can easily lead to confusion in understanding the concept as phenotypic. For example, to say that &ldquogreen peas&rdquo dominate &ldquoyellow peas&rdquo confuses inherited genotypes and expressed phenotypes. This will subsequently confuse discussion of the molecular basis of the phenotypic difference. Dominance is not inherent. One allele can be dominant to a second allele, recessive to a third allele, and codominant to a fourth. If a genetic trait is recessive, a person needs to inherit two copies of the gene for the trait to be expressed. Thus, both parents have to be carriers of a recessive trait in order for a child to express that trait.

Since Mendel&rsquos experiments with pea plants, other researchers have found that the law of dominance does not always hold true. Instead, several different patterns of inheritance have been found to exist.


Introduction to Genetics: Genetics Terminologies (Concept of Genetics: Definition of Terminologies in Genetics)

Ø Genetics: Genetics is the study of Heredity and Variation of Inherited Characters.
Ø Heredity: The tendency offspring to resemble their parents is called heredity.
Ø Variation: The tendency of offspring to vary from their parents is called variation.
Ø The term ‘Genetics’ was coined by William Bateson in 1905
Ø Genetics is a relatively young branch of biological science.
Ø The study of genetics started with the work of Gregor Johan Mendel (Father of Modern Genetics)

Ø Today, many modern branches of genetics are there such as Cytogenetics, Molecular Genetics, Phylogenetics, Developmental Genetics and Behavioral Genetics.

Contribution of Mendel in Genetics

Ø Gregor Johan Mendel (1822 – 1884), an Austrian Monk, is known as the “Father of Modern Genetics”.

Ø The Modern Concepts of Genetics took birth from his pioneering work on Pisum sativum (Garden Pea).

Ø Mendel published his results in the annual Proceedings of the Natural History Society of Brunn in 1866.

Ø The title of his publication: Experiments in Plant Hybridization (German).

Ø Mendel died as an unrecognized man His studies remain in dark for about 34 years.

Rediscovery of Mendel’s original work

Ø In 1900, three scientists independently rediscovered Mendel’s work.

@. Erich von Tschermak (Austia)

Ø Mendel’s findings were now known as Mendelism or Mendelian Lows of Inheritance.

Terminologies in Genetics

Ø The term ‘Gene’ was coined by Johanson in 1909.

Ø Definition: Gene is the hereditary determining factor and it consists of a continuous segment of DNA.

Ø In eukaryotes, the gene occupies in a specific position on the chromosome called locus (plural loci).

Ø Alleles are also called as allelomorphs.

Ø Definition: Alleles are alternating forms of a gene which occupy identical loci on the homologous chromosome.

Ø The allele controls the contrasting characters of the same trait.

Ø Usually, the alleles exist in TWO different forms: (1) Dominant allele and (2) Recessive allele

(3). Dominant and Recessive Alleles

Ø The Dominant allele will always express phenotypically.

Ø The Recessive alleles will express only in the absence of a dominant allele.

Ø The dominant alleles masks or suppress the expression of the recessive alleles.

Ø Dominant alleles are classically symbolized with English capital letters (Example: Tall – T).

Ø Recessive alleles are symbolized with small letters (Example: Dwarf – t).

(4). Genotype and Phenotype

Ø Genotype: Genotype is the genetic makeup (constitution) of an organism.

Ø Phenotype: Phenotype is the physical features/appearance of an organism.

Ø The phenotype is the expression of genotype in an organism.

Ø The phenotype is produced not only by the genotype but also by the interaction between the genotype and environmental factors. (Example: If a pea plant with genotype TT will only be tall if the soil is sufficiently rich to provide nutrients and water).

Ø Trait: Height
Ø Phenotype : Tall and Dwarf
Ø Genotype: TT or Tt and tt

(5). Homozygous

Ø Homozygous is a condition in which both the members of an allelic pair in the homologous chromosome are identical (either dominant or recessive allele).

Ø Homozygous individuals are pure or true-breeding. They produce only one type of gamete with specific to particular gene.

(6). Heterozygous:

Ø Heterozygous is a condition in which the members of an allelic pair in the homologous chromosome are NOT identical (one dominant and one recessive allele).

Ø Heterozygous individuals are the progenies of hybridization.

Ø They cannot be tree-breeding. They produce different types of gametes with specific to particular gene.

(7). Hemizygous

Ø Hemizygous is a condition when the gene is present only in one copy.

Ø The hemizygous condition is observed usually in male individuals.

o Genes on the X chromosome of a male are hemizygous since males have only one X chromosome)

o Similarly, the genes on Y the chromosome in a male are also hemizygous (only one Y chromosome in males).

(8). Dominance

Ø Dominance is the ability of an allele to express itself phenotypically both in homozygous (TT) and in heterozygous (Tt) conditions.

(9). Recessiveness:

Ø Recessiveness is the inability of an allele to manifest its phenotype in heterozygous (Tt) condition.

Ø In the example (Tt), ‘t’ is recessive since it fails to express its phenotype in the presence of a dominant gene ‘T’.

(10). Hybridization and Hybrid

Ø Hybridization is the process of crossing of two genetically different individuals.

Ø Hybrid: The progeny of hybridization is called the hybrid.

(11). Monohybrid

Ø A monohybrid is an organism which is heterozygous with respect to only ONE pair of allele at a locus under study.

Ø Example: Tall (TT) X Dwarf (tt)

(12). Dihybrid

Ø A dihybrid is an organism which is heterozygous with respect to TWO pairs of alleles at two loci under study.

Ø Example: Yellow Round (YYRR) X Green Wrinkled (yyrr)

(13). Monohybrid Cross

Ø Monohybrid cross is a cross between two individuals which differ from each other with respect to ONE pair of allele under study

Ø Example: Tall (TT) X Dwarf (tt) = Tall (Tt)

(14). Dihybrid Cross

Ø A dihybrid cross is a cross between two individuals which differ from each other with respect to TWO pairs of allele under study.

Ø Yellow Round (YYRR) X Green Wrinkled (yyrr) = Yellow Round (YyRr)

(15). F1 and F2 Generation

Ø The ‘F’ stands for Filial meaning son.

Ø F1 generation is the FIRST generation progeny of hybridization.

Ø F2 generation is the progeny of hybrid (F1) when it is selfed or crossed with its siblings.

(16). Reciprocal Cross

Ø Reciprocal cross means two reverse crosses in which the sexes of the parents are interchanged.

Ø If the traits are autosomal, the reciprocal cross always yields same result.

Ø If the traits are on sex chromosomes, the reciprocal cross gives different results.

(17). Backcross

Ø Backcross is the cross (hybridization) of F1 progeny with one of its parents.

Ø If the F1 is crossed with the dominant parent, all the progenies (F2) will be with dominant phenotype.

Ø If the F1 is crossed with the recessive parent, individuals with both phenotypes (dominant and recessive) will appear in equal proportions.

Ø The ratio of progenies produced during the back cross is called back cross ratio.

(18). Test Cross

Ø A test cross is a type of backcross in which the F1 progeny is crossed with its double recessive parent.

Ø A test cross is used to determine whether the individuals of the F1 exhibiting dominant character are homozygous or heterozygous

Ø In other words, a test cross is performed to detect the genotype of F1progeny.


Dominant and Recessive Alleles

If an individual has two different alleles for a particular gene, the dominant allele will determine the phenotype. For example, in pea flowers allele P may produce purple pigment and allele p may produce no pigment, resulting in a white flower. A cross between a PP parent who carries two alleles for purple pigment and a pp parent who carries two alleles for no pigment will result in offspring with one of each allele. The offspring will have a Pp genotype and the phenotype will be purple flowers because the P allele is dominant and the p allele is recessive.