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16.5: Non-Mendelian Inheritance - Biology


Family Portrait

This photo of a South African family shows some of the variations that exist in human skin color. The color of human skin can range from very light to very dark with every possible gradation in between. As you might expect, the skin color trait has a more complex genetic basis than just one gene with two alleles, which is the type of simple trait that Mendel studied in pea plants. Like skin color, many other human traits have more complicated modes of inheritance than Mendelian traits. Such modes of inheritance are called non-Mendelian inheritance, and they include inheritance of multiple allele traits, traits with codominance or incomplete dominance, and polygenic traits, among others, all of which are described below.

Multiple Allele Traits

The majority of human genes are thought to have more than two normal versions or alleles. Traits controlled by a single gene with more than two alleles are called multiple allele traits. An example is ABO blood type. Your blood type refers to which of certain proteins called antigens are found on your red blood cells. There are three common alleles for this trait, which are represented by the letters IA, IB, and i.

Table (PageIndex{1}): ABO Blood Group
GenotypePhenotype (blood type)
IAIAA

IAi

A
IBIBB
IBiB
iiO
IAIBAB

As shown in the table below, there are six possible ABO genotypes because the three alleles, taken two at a time, result in six possible combinations. The IA and IB alleles are dominant to the i allele. As a result, both IAIA and IAi genotypes have the same phenotype, with the A antigen in their blood (type A blood). Similarly, both IBIB and IBi genotypes have the same phenotype, with the B antigen in their blood (type B blood). No antigen is associated with the i allele, so people with the ii genotype have no antigens for ABO blood type in their blood (type O blood).

Codominance

Look at the genotype IAIB in the ABO blood group table. Alleles IA and IB for ABO blood type are neither dominant nor recessive to one another. Instead, they are codominant to each other. Codominance occurs when two alleles for a gene are expressed equally in the phenotype of heterozygotes. In the case of ABO blood type, IAIB heterozygotes have a unique phenotype, with both A and B antigens in their blood (type AB blood).

Incomplete Dominance

Another relationship that may occur between alleles for the same gene is incomplete dominance. This occurs when the dominant allele is not completely dominant, so an intermediate phenotype results in heterozygotes who inherit both alleles. Generally, this happens when the two alleles for a given gene both produce proteins but one protein is not functional. As a result, the heterozygote individual produces only half the amount of normal protein as is produced by an individual who is homozygous for the normal allele.

An example of incomplete dominance in humans is Tay Sachs disease. The normal allele for the gene, in this case, produces an enzyme that is responsible for breaking down lipids. A defective allele for the gene results in the production of a nonfunctional enzyme. Heterozygotes who have one normal and one defective allele produce half as much functional enzyme as the normal homozygote, and this is enough for normal development. However, homozygotes who have only defective alleles produce only the nonfunctional enzyme. This leads to the accumulation of lipids in the brain beginning in utero, which causes significant brain damage. Most individuals with Tay Sachs disease die at a young age, typically by the age of five years.

Polygenic Traits

Many human traits are controlled by more than one gene. These traits are called polygenic traits. The alleles of each gene have a minor additive effect on the phenotype. There are many possible combinations of alleles, especially if each gene has multiple alleles. Therefore, a whole continuum of phenotypes is possible.

An example of a human polygenic trait is adult height. Several genes, each with more than one allele, contribute to this trait, so there are many possible adult heights. For example, one adult’s height might be 1.655 m (5.430 feet), and another adult’s height might be 1.656 m (5.433 feet). Adult height ranges from less than 5 feet to more than 6 feet, with males being somewhat taller than females on average. The majority of people fall near the middle of the range of heights for their sex, as shown in the graph in Figure (PageIndex{2}).

Environmental Effects on Phenotype

Many traits are affected by the environment as well as by genes. This may be especially true for polygenic traits. For example, adult height might be negatively impacted by poor diet or illness during childhood. Skin color is another polygenic trait. There is a wide range of skin colors in people worldwide. In addition to differences in skin color genes, differences in exposure to ultraviolet (UV) light cause some of the variations. As shown in Figure (PageIndex{3}), exposure to UV light darkens the skin.

Pleiotropy

Some genes affect more than one phenotypic trait. This is called pleiotropy. There are numerous examples of pleiotropy in humans. They generally involve important proteins that are needed for the normal development or functioning of more than one organ system. An example of pleiotropy in humans occurs with the gene that codes for the main protein in collagen, a substance that helps form bones. This protein is also important in the ears and eyes. Mutations in the gene result in problems not only in bones but also in these sensory organs, which is how the gene's pleiotropic effects were discovered.

Another example of pleiotropy occurs with sickle cell anemia. This recessive genetic disorder occurs when there is a mutation in the gene that normally encodes the red blood cell protein called hemoglobin. People with the disorder have two alleles for sickle-cell hemoglobin, so named for the sickle shape (Figure (PageIndex{4})) that their red blood cells take on under certain conditions such as physical exertion. The sickle-shaped red blood cells clog small blood vessels, causing multiple phenotypic effects, including stunting of physical growth, certain bone deformities, kidney failure, and strokes.

Epistasis

Some genes affect the expression of other genes. This is called epistasis. Epistasis is similar to dominance, except that it occurs between different genes rather than between different alleles for the same gene.

Albinism is an example of epistasis. A person with albinism has virtually no pigment in the skin. The condition occurs due to an entirely different gene than the genes that encode skin color. Albinism occurs because a protein called tyrosinase, which is needed for the production of normal skin pigment, is not produced due to a gene mutation. If an individual has albinism mutation, he or she will not have any skin pigment, regardless of the skin color genes that were inherited.

Feature: My Human Body

Do you know your ABO blood type? In an emergency, knowing this valuable piece of information could possibly save your life. If you ever need a blood transfusion, it is vital that you receive blood that matches your own blood type. Why? If the blood transfused into your body contains an antigen that your own blood does not contain, antibodies in your blood plasma (the liquid part of your blood) will recognize the antigen as foreign to your body and cause a reaction called agglutination. In this reaction, the transfused red blood cells will clump together, as shown in the image below. The agglutination reaction is serious and potentially fatal.

Knowing the antigens and antibodies present in each of the ABO blood types will help you understand which type(s) of blood you can safely receive if you ever need a transfusion. This information is shown in the table below for all of the ABO blood types. For example, if you have blood type A, this means that your red blood cells have the A antigen and that your blood plasma contains anti-B antibodies. If you were to receive a transfusion of type B or type AB blood, both of which have the B antigen, your anti-B antibodies would attack the transfused red blood cells, causing agglutination.

Table (PageIndex{2}): Antigens and antibodies in ABO blood types
CharacteristicsType AType BType ABType O
Red Blood Cell
Antibodies in Plasma

Anti-B

Anti-A

None

Anti-A and Anti-B

Antigens in Red Blood Cells

A antigen

B antigens

A and B antigens

None

You may have heard that people with blood type O are called universal donors and that people with blood type AB are called universal recipients. People with type O blood have neither A nor B antigens in their blood, so if their blood is transfused into someone with a different ABO blood type, it causes no immune reaction. In other words, they can donate blood to anyone. On the other hand, people with type AB blood have no anti-A or anti-B antibodies in their blood, so they can receive a transfusion of blood from anyone. Which blood type(s) can safely receive a transfusion of type AB blood, and which blood type(s) can be safely received by those with type O blood?

Review

  1. What is non-Mendelian inheritance?
  2. Explain why the human ABO blood group is an example of a multiple allele trait with codominance.
  3. What is incomplete dominance? Give an example of this type of non-Mendelian inheritance in humans.
  4. Explain the genetic basis of human skin color.
  5. How may the human trait of adult height be influenced by the environment?
  6. Define pleiotropy, and give a human example.
  7. What is the difference between pleiotropy and epistasis?
  8. Which of the following terms best matches each trait description? Choose only the one term that best fits each trait. (codominance; multiple allele trait; Mendelian trait; polygenic trait)
    1. A trait controlled by four genes.
    2. A trait where each allele of a heterozygote makes an equal contribution to the phenotype.
    3. A trait controlled by a single gene that has three different versions.
    4. A trait controlled by a single gene where one allele is fully dominant to the only other allele.
  9. People with type AB blood have:
    1. anti-O antibodies
    2. anti-A and anti-B antibodies
    3. A and B antigens
  10. True or False. People with type O blood cannot receive a blood transfusion from anyone besides others with type O blood.
  11. True or False. People with type O blood can be heterozygous for this trait.

Explore More

To learn more about non-Mendelian Inheritance, check out this video:


Difference Between Mendelian and Non Mendelian Inheritance

The patterns of inheritance in sexual reproduction are described by means of Mendelian and non Mendelian inheritance. A set of characters or traits passes from parents to offspring during reproduction. These characters pass through generations by the inheritance of genetic material through sex cells. Each character is determined by a particular gene in the genome. The alternative forms of a gene are referred to as alleles. The main difference between Mendelian and non Mendelian inheritance is that Mendelian inheritance describes the determination of traits by means of dominant and recessive alleles of a particular gene whereas non Mendelian inheritance describes the inheritance of traits which does not follow Mendelian laws.

Key Areas Covered

Key Terms: Codominance, Incomplete Dominance, Law of Dominance, Laws of Inheritance, Law of Independent Assortment, Law of Segregation, Mendelian Inheritance, Multiple Alleles, Non Mendelian Inheritance, Offspring, Phenotypic Plasticity, Polygenic Inheritance, Sex-Linked Inheritance, Traits


16.5) Sex hormones in humans

Puberty is the stage in life when a child’s body develops into an adult’s body. The changes take place gradually, usually between the ages of 10 and 16.

Changes occur at puberty because of hormones:

  • testosterone – produced by the testes – controls the development of male secondary sexual characteristics
  • oestrogen – produced by the ovaries – controls the development of female secondary sexual characteristics

  • The ovaries release an ovum about every 4 weeks.
  • In preparation for this the lining of the uterus wall thickens, so that an embryo can embed itself if the release ovum is fertilised.
  • If no implantation occurs, the uterus lining breaks down. The cells, along with blood are passed out of the vagina. This is called a menstrual period.
  • Several hormones control this cycle:


Sex-Linked Traits

Sex-linked traits occur when an allele is located on the X-chromosome. A lot of hereditary diseases, like hemophilia and cystic fibrosis, are sex-linked. These traits can either be dominant or recessive. If the trait is dominant, than every individual that receives an X-chromosome with the allele will display these traits. If the trait is recessive, then every male with the allele will display the traits. Female offspring will only display the traits if both of their their X-chromosomes have the recessive allele.

Let’s look at the difference between dominant and recessive sex-linked traits (Figure 3). In both examples, the father is unaffected and the mother only has one affected X-chromosome.

Figure 3. Compare dominant and recessive sex-linked traits.

Practice Question

Colorblindness is a recessive sex-linked trait. Which of the following must be true for two parents to produce a colorblind daughter?

Remember that in incomplete dominance, the two traits blend together in co-dominance, the two traits are equally expressed and in sex-linked traits, the traits can be dominant or recessive, but they always appear on the X-chromosome.


Multiple Interactive Gene Loci

Both of the examples above illustrate exceptions to the monohybrid inheritance pattern. Variants to the dihybrid pattern are seen when two different gene loci each contribute to the same phenotype, e.g. feather color in budgies. Color in bird feathers depends on two things: pigment deposited in the feather and tiny ridges on the feather that produce iridescence. Budgie feathers may have yellow or no pigment from one set of gene loci, and blue or no iridescence from the presence or absence of the ridges. Various combinations of these colors produce white, yellow, green, or blue feathers. Green birds have both the pigment and the iridescence white birds have neither. A dihybrid cross between two birds heterozygous at both loci will produce a typical 9:3:3:1 ratio, but the ratio is expressed in a single trait: feather color.

In mice, among the many gene loci that affect coat color are the albino locus and the agouti locus. To express the typical mousy gray coat color a mouse must have a normal allele at the albino locus and the normal agouti allele at the agouti locus. Mice that are homozygous for the recessive albinism gene are white. Mice that are homozygous for the recessive nonagouti gene at the agouti locus are black. Mice may, therefore, be agouti (gray), black or white. Crossing two mice that are heterozygous at both loci produces a modification of the 9:3:3:1 ratio: 9 agouti mice, 3 black mice, and 4 albinos. This is because homozygosity for the albino gene blocks expression of both the agouti and the black phenotypes.

In the next tutorial, learn about the effects of chromosomal mutations, such as nondisjunction, deletion, and duplication.

This worksheet will test the student’s aptitude on Non-Mendelian inheritance. The first part will test the student’s comprehension of complete dominance, incomplete dominance, and codominance. The second part is a practice on logical relations between incomplete dominance and codominance through a Venn diagram.


Incomplete Dominance

With codominant alleles, both traits are expressed at the same time. With incomplete dominance, the same thing occurs—but the traits are blended together just like paint mixed together, rather than occurring in discrete patches like the speckled flowers.

Going back to our flower example, if flower color shows incomplete dominance then two different flowers crossed together will produce a hybrid that’s in between both of the parents. So, for example, if you cross a white flower with a red flower, you would get a pink flower if the two alleles showed incomplete dominance.


Non-Mendelian inheritance

Non-Mendelian Inheritance
Master Non-Mendelian Patterns of Inheritance
Non-Mendelian Inheritance Definition .

Non-Mendelian Inheritance
Polygenic traits are complex and unable to be explained by simple Mendelian inheritance alone. Mendelian inheritance is involved when one particular gene controls for a trait, and the traits are discrete.

[edit]
In 2005, scientists at Purdue University proposed that Arabidopsis possessed an alternative to previously known mechanisms of DNA repair, which one scientist called a "parallel path of inheritance". It was observed in mutations of the HOTHEAD gene.

patterns such as incomplete dominance, codominance, multiple alleles, and sex linkage from the results of crosses
Explain the effect of linkage and recombination on gamete genotypes
Explain the phenotypic outcomes of epistatic effects among genes
Explain polygenic inheritance .

This will show apparent significant deviations from Hardy- Weinberg equilibrium and

of alleles (Donnelly et al., 1999). Homozygote individuals found in excess in different populations of W. attu in the present study could be due to null alleles or by a real biological phenomenon.

due to extra-nuclear DNA (mitochondrial DNA in animals). The transmission of the trait only occurs from mothers.


Master Non-Mendelian Patterns of Inheritance

There are many types of inheritance that do not follow the Mendelian pattern. Notable ones include: multiple alleles, gene interactions (complementary genes, epistasis and quantitative or polygenic, inheritance), linkage with or without crossing over and sex-linked inheritance.

Pleiotropy, the lack of dominance and lethal genes cannot be classified as variations of inheritance since genes can have these behaviors and at the same time obey Mendelian laws.

Mutations and aneuploidies are abnormalities that alter the Mendelian pattern of inheritance as well as mitochondrial inheritance (the passage of mitochondrial DNA from the mother through the cytoplasm of the egg cell to the offspring).

Lack of Dominance

More Bite-Sized Q&As Below

2. What is the genetic condition in which the heterozygous individual has a different phenotype from the homozygous individual?

This condition is called lack of dominance and it can happen in two ways: incomplete dominance or codominance.

In incomplete dominance, the heterozygous individual presents an intermediate phenotype between the two types of homozygous ones, such as in sickle cell anemia, in which the heterozygous individual produces some sick red blood cells and some normal red blood cells. Codominance occurs, for example, in the genetic determination of the MN blood group system, in which the heterozygous individual has a phenotype totally different from the homozygous one, and not an intermediate form.

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Pleiotropy

3. What is pleiotropy?

Pleiotropy (or pliotropy) is the phenomenon in which a single gene conditions several different phenotypical traits.

Some phenotypical traits may be sensitive to the pleiotropic effects (for example, inhibition) of other genes, even when conditioned by a pair of alleles in simple dominance. A mixture of pleiotropy and gene interaction is characteristic of these cases.

Lethal Genes

4. What are lethal genes?

Lethal genes are genes with at least one allele that, when present in the genotype of an individual, cause death. There are recessive lethal alleles and dominant lethal alleles. (There are also genes with alleles that are dominant when in heterozygosity but lethal when in homozygosity, meaning that the dominance related to the phenotype does not correspond to the dominance related to lethality.)

Multiple Alleles

5. What are multiple alleles? Is there dominance in multiple alleles?

Multiple alleles is the phenomenon in which the same gene has more than two different alleles (in normal Mendelian inheritance, the gene only has two alleles). Obviously, these alleles combine in pairs to form genotypes.

In multiple alleles, relative dominance among the alleles may exist. A typical example of multiple alleles is the inheritance of the ABO blood group system, in which there are three alleles (A, B or O, or IA, IB and i). IA is dominant over i, which is recessive in relation to the other IB allele. IA and IB lack dominance between themselves.

Another example is the color of rabbit fur, which is conditioned by four different alleles (C, Cch, Ch and c). In this case, the dominance relations are C > Cch > Ch > c (the symbol > means “is dominant over”).

Complementary Genes

6. What are gene interactions? What are the three main types of gene interactions?

Gene interactions are the phenomenon in which a given phenotypic trait is conditioned਋y two or more genes (do not confuse this with multiple alleles, in which there is a single gene with three or more alleles).

The three main types of gene interaction are: complementary genes, epistasis and polygenic inheritance (or quantitative inheritance).

7. What are complementary genes? Does this inheritance pattern obey Mendel’s second law?

Complementary genes are different genes that act together to determine a given phenotypic trait.

For example, consider a phenotypical trait conditioned by 2 complementary genes whose alleles are respectively X, x, Y and y. Performing hybridization in F2, 4 different phenotypic forms are obtained: X_Y_ (double dominant), X_yy (dominant for the first pair, recessive for the second), xxY_ (recessive for the first pair, dominant for the second) and xxyy (double recessive). This is what happens, for example, in the color of budgie feathers, in which the double dominant interaction results in green feathers the interaction that is dominant for the first pair and recessive for the second results in yellow feathers the interaction that is recessive for the first pair and dominant for the second leads to blue feathers and the double recessive interaction leads to white feathers.

Each complementary gene segregates independently from the others since they are located in different chromosomes. Therefore, the pattern follows Mendel’s second law (although it does not obey Mendel’s first law).

Epistasis

8. What is epistasis? What is the difference between dominant epistasis and recessive epistasis?

Epistasis is the gene interaction in which a gene (the epistatic gene) can disallow the phenotypical manifestation of another gene (the hypostatic gene). In dominant epistasis, the inhibitor allele is the dominant allele (for example, I) of the epistatic gene and, as result, inhibition occurs in dominant homozygosity (II) or in heterozygosity (Ii). In recessive epistasis, the inhibitor allele is the recessive allele of the epistatic gene (i) and, as a result, inhibition occurs only in recessive homozygosity (ii).

9. In the hybridization of 2 genes (4 different alleles, 2 of each pair), how does epistasis affect the proportion of phenotypic forms in the F2 generation?

In dihybridism without epistasis, double heterozygous parents cross-breed and ਄ phenotypical forms appear in F2. The proportion is 9 individuals double dominant, 3 individuals dominant for the first pair and recessive for the second pair, 3 individuals recessive for the first pair and dominant for the second pair, and 1 individual double recessive (9:3:3:1).

Considering that the epistatic gene is the second pair and that the recessive genotype of the hypostatic gene implies the lack of the characteristic, in the F2 generation of dominant epistasis, the following phenotypic forms would emerge: 13 individuals dominant for the second pair or recessive for the first pair, meaning that, the characteristic is not manifest 3 individuals dominant for the first pair and recessive for the second pair, meaning that the characteristic is manifest. The phenotypical proportion would be 13:3. In recessive epistasis, the phenotypical forms that would emerge in F2 are: 9 individuals double dominant (the characteristic is manifest) and 7 individuals recessive for the first pair or recessive for the second pair, meaning that the characteristic is not manifest. Therefore, the phenotypical proportion would be 9:7.

These examples show how epistasis changes phenotypical forms and proportions, from the normal 9:3:3:1 in F2 to 13:3 in dominant epistasis or to 9:7 in recessive epistasis (note that some forms have even disappeared).

(If the recessive genotype of the hypostatic gene is active, not only meaning that the dominant allele is not manifest, the number of phenotypic forms in F2 changes.) 

Polygenic Inheritance

10. What is polygenic inheritance? How does it work?

Polygenic inheritance, also known as quantitative inheritance, is the gene interaction in which a given trait is conditioned by several different genes with alleles that may or may not contribute to increasing the intensity of the phenotype. These alleles may be contributing or non-contributing and there is no dominance among them. Polygenic inheritance is the type of inheritance, for example, of skin color and stature in humans.

Considering a given species of animal in which the length of the individual is conditioned by the polygenic inheritance of three genes, for the genotype with only non-contributing alleles (aabbcc), a basal phenotype, for example, 30 cm, would emerge. Also considering that, for each contributing allele, a 5 cm increase in the length of the animal is added, in the genotype with only contributing alleles (AABBCC), the animal would present the basal phenotype (30 cm) plus 30 cm more added for each contributing allele, that is, its length would be 60 cm. In the case of triple heterozygosity, for example, the length of the animal would be 45 cm. That is the way polygenic inheritance works.

11. What is the most likely inheritance pattern of a trait with Gaussian proportional distribution of phenotypic forms?

If a trait statistically has a normal (Gaussian, bell curve) distribution of its phenotypical forms, it is probable that it is conditioned by polygenic inheritance (quantitative inheritance).

In quantitative inheritance, the effects of several genes are added to others, making it possible to represent the trait variation of a given population in a Gaussian curve with the heterozygous genotypes in the center, that is, those that appear in larger number, and the homozygous ones on the ends.

12. How can you find the number of pairs of alleles involved in polygenic inheritance by using the number of phenotypic forms of the trait they condition?

Considering “p” the number of phenotypicਏorms and “a” the number of alleles involved in the polygenic inheritance, the formula p = 2a + 1 applies.

(Often, it is not possible to precisely determine the number of phenotypic forms, p, due to the multigenic nature of inheritance, since the observed variation of phenotypes often seems to be a continuum or the trait may suffer from environmental influences.)

Sex-linked Inheritance

13. Why is sex-linked inheritance an example of non-Mendelian inheritance?

Sex-linked inheritance is a type of non-Mendelian inheritance because it opposes Mendel’s first law, which postulates that each trait is always conditioned by two factors (alleles). In non-homologous regions of sex chromosomes, the genotypes of the genes contain only one allele (even in the case of the XX karyotype, in women, one of the X chromosomes is inactive).

Mitochondrial Inheritance

14. What is mitochondrial inheritance?

Mitochondrial inheritance is the passing down of mitochondrial DNA molecules (mtDNA) to the offspring. An individual's entire stock of mtDNA must come from the mother, the maternal grandmother, the maternal great grandmother and so on, since mitochondria are inherited from the cytoplasm of the egg cell (that later composes the cytoplasm of the zygote).

There are several genetic diseases caused by mitochondrial inheritance, such as Leber's hereditary optic neuropathy, which leads to loss of the central vision of both eyes, and Kearns-Sayre syndrome, a neuromuscular disease that causes ophthalmoplegia and muscle fatigue.

Mitochondrial inheritance is an excellent means for the genetic analysis of maternal lineage (just like the Y chromosome is an excellent means of studying paternal lineage).

Now that you have finished studying Non-Mendelian Inheritance, these are your options:


Contents

Incomplete dominance Edit

In cases of intermediate inheritance due to incomplete dominance, the principle of dominance discovered by Mendel does not apply. Nevertheless, the principle of uniformity works, as all offspring in the F1-generation have the same genotype and same phenotype. Mendel's principle of segregation of genes applies too, as in the F2-generation homozygous individuals with the phenotypes of the P-generation appear. Intermediate inheritance was first examined by Carl Correns in Mirabilis jalapa he used for further genetic experiments. [2] Antirrhinum majus also shows intermediate inheritance of the pigmentation of the blossoms. [3]

Co-dominance Edit

In cases of co-dominance, the genetic traits of both different alleles of the same gene-locus are clearly expressed in the phenotype. For example, in certain varieties of chicken, the allele for black feathers is co-dominant with the allele for white feathers. Heterozygous chickens have a colour described as "erminette", speckled with black and white feathers appearing separately. Many human genes, including one for a protein that controls cholesterol levels in the blood, show co-dominance too. People with the heterozygous form of this gene produce two different forms of the protein, each with a different effect on cholesterol levels.

Genetic linkage Edit

When genes are located on the same chromosome and no crossing over took place before the segregation of the chromosomes into the gametes, the genetic traits will be inherited in connection, because of the genetic linkage. These cases constitute an exception to the Mendelian rule of independent assortment.

Multiple alleles Edit

In Mendelian inheritance, genes have only two alleles, such as a and A. Mendel consciously chose pairs of genetic traits, represented by two alleles for his inheritance experiments. In nature, such genes often exist in several different forms and are therefore said to have multiple alleles. An individual, of course, usually has only two copies of each gene, but many different alleles are often found within a population. A rabbit's coat color is determined by a single gene that has at least four different alleles. They display a pattern of a dominance-hierarchy that can produce four coat colors. In the genes for the dog coat colours there are four alleles on the Agouti-locus. The allele "aw" is dominant over the alleles "at" and "a" but recessive under "Ay".

Many other genes have multiple alleles, including the human genes for ABO blood type.

Epistasis Edit

If one or more genes cannot be expressed because of another genetic factor hindering their expression, this epistasis can make it impossible even for dominant alleles on certain other gene-loci to have an effect on the phenotype. An example in dog coat genetics is the homozygosity with the allele "e e" on the Extension-locus making it impossible to produce any other pigment than pheomelanin. Although the allele "e" is a recessive allele on the extension-locus itself, the presence of two copies leverages the dominance of other coat colour genes. Domestic cats have a gene with a similar effect on the X-chromosome.

Sex-linked inheritance Edit

Genetic traits located on gonosomes sometimes show specific non-Mendelian inheritance patterns. Individuals can develop a recessive trait in the phenotype dependent on their sex—for example, colour blindness and haemophilia (see gonosomal inheritances). [6] [7] As many of the alleles are dominant or recessive, a true understanding of the principles of Mendelian inheritance is an important requirement to also understand the more complicated inheritance patterns of sex-linked inheritances.

Extranuclear inheritance Edit

Extranuclear inheritance (also known as cytoplasmic inheritance) is a form of non-Mendelian inheritance also first discovered by Carl Correns in 1908. [8] While working with Mirabilis jalapa, Correns observed that leaf colour was dependent only on the genotype of the maternal parent. Based on these data, he determined that the trait was transmitted through a character present in the cytoplasm of the ovule. Later research by Ruth Sager and others identified DNA present in chloroplasts as being responsible for the unusual inheritance pattern observed. Work on the poky strain of the mould Neurospora crassa begun by Mary and Hershel Mitchell [9] ultimately led to the discovery of genetic material in the mitochondria, the mitochondrial DNA.

According to the endosymbiont theory, mitochondria and chloroplasts were once free-living organisms that were each taken up by a eukaryotic cell. [10] Over time, mitochondria and chloroplasts formed a symbiotic relationship with their eukaryotic hosts. Although the transfer of a number of genes from these organelles to the nucleus prevents them from living independently, each still possesses genetic material in the form of double stranded DNA.

It is the transmission of this organellar DNA that is responsible for the phenomenon of extranuclear inheritance. Both chloroplasts and mitochondria are present in the cytoplasm of maternal gametes only. Paternal gametes (sperm for example) do not have cytoplasmic mitochondria. Thus, the phenotype of traits linked to genes found in either chloroplasts or mitochondria are determined exclusively by the maternal parent.

In humans, mitochondrial diseases are a class of diseases, many of which affect the muscles and the eye.

Polygenic traits Edit

Many traits are produced by the interaction of several genes. Traits controlled by two or more genes are said to be polygenic traits. Polygenic means "many genes" are necessary for the organism to develop the trait. For example, at least three genes are involved in making the reddish-brown pigment in the eyes of fruit flies. Polygenic traits often show a wide range of phenotypes. The broad variety of skin colour in humans comes about partly because at least four different genes probably control this trait.

Non-random segregation Edit

Non-random segregation of chromosomes is a deviation from the usual distribution of chromosomes during meiosis and in some cases of mitosis.

Gene conversion Edit

Gene conversion can be one of the major forms of non-Mendelian inheritance. Gene conversion arises during DNA repair via DNA recombination, by which a piece of DNA sequence information is transferred from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered. This may occur as a mismatch repair between the strands of DNA which are derived from different parents. Thus the mismatch repair can convert one allele into the other. This phenomenon can be detected through the offspring non-Mendelian ratios, and is frequently observed, e.g., in fungal crosses. [11]

Infectious heredity Edit

Another form of non-Mendelian inheritance is known as infectious heredity. Infectious particles such as viruses may infect host cells and continue to reside in the cytoplasm of these cells. If the presence of these particles results in an altered phenotype, then this phenotype may be subsequently transmitted to progeny. [12] Because this phenotype is dependent only on the presence of the invader in the host cell's cytoplasm, inheritance will be determined only by the infected status of the maternal parent. This will result in a uniparental transmission of the trait, just as in extranuclear inheritance.

One of the most well-studied examples of infectious heredity is the killer phenomenon exhibited in yeast. Two double-stranded RNA viruses, designated L and M, are responsible for this phenotype. [13] The L virus codes for the capsid proteins of both viruses, as well as an RNA polymerase. Thus the M virus can only infect cells already harbouring L virus particles. The M viral RNA encodes a toxin that is secreted from the host cell. It kills susceptible cells growing in close proximity to the host. The M viral RNA also renders the host cell immune to the lethal effects of the toxin. For a cell to be susceptible it must therefore be either uninfected or harbour only the L virus.

The L and M viruses are not capable of exiting their host cell through conventional means. They can only transfer from cell to cell when their host undergoes mating. All progeny of a mating involving a doubly infected yeast cell will also be infected with the L and M viruses. Therefore, the killer phenotype will be passed down to all progeny.

Heritable traits that result from infection with foreign particles have also been identified in Drosophila. Wild-type flies normally fully recover after being anesthetized with carbon dioxide. Certain lines of flies have been identified that die off after exposure to the compound. This carbon dioxide sensitivity is passed down from mothers to their progeny. This sensitivity is due to infection with σ (Sigma) virus, a rhabdovirus only capable of infecting Drosophila. [14]

Although this process is usually associated with viruses, recent research has shown that the Wolbachia bacterium is also capable of inserting its genome into that of its host. [15] [16]

Genomic imprinting Edit

Genomic imprinting represents yet another example of non-Mendelian inheritance. Just as in conventional inheritance, genes for a given trait are passed down to progeny from both parents. However, these genes are epigenetically marked before transmission, altering their levels of expression. These imprints are created before gamete formation and are erased during the creation of germ line cells. Therefore, a new pattern of imprinting can be made with each generation.

Genes are imprinted differently depending on the parental origin of the chromosome that contains them. In mice, the insulin-like growth factor 2 gene undergoes imprinting. The protein encoded by this gene helps to regulate body size. Mice that possess two functional copies of this gene are larger than those with two mutant copies. The size of mice that are heterozygous at this locus depends on the parent from which the wild-type allele came. If the functional allele originated from the mother, the offspring will exhibit dwarfism, whereas a paternal allele will generate a normal-sized mouse. This is because the maternal Igf2 gene is imprinted. Imprinting results in the inactivation of the Igf2 gene on the chromosome passed down by the mother. [17]

Imprints are formed due to the differential methylation of paternal and maternal alleles. This results in differing expression between alleles from the two parents. Sites with significant methylation are associated with low levels of gene expression. Higher gene expression is found at unmethylated sites. [18] In this mode of inheritance, phenotype is determined not only by the specific allele transmitted to the offspring, but also by the sex of the parent that transmitted it.

Mosaicism Edit

Individuals who possess cells with genetic differences from the other cells in their body are termed mosaics. These differences can result from mutations that occur in different tissues and at different periods of development. If a mutation happens in the non-gamete forming tissues, it is characterized as somatic. Germline mutations occur in the egg or sperm cells and can be passed on to offspring. [19] Mutations that occur early on in development will affect a greater number of cells and can result in an individual that can be identified as a mosaic strictly based on phenotype.

Mosaicism also results from a phenomenon known as X-inactivation. All female mammals have two X chromosomes. To prevent lethal gene dosage problems, one of these chromosomes is inactivated following fertilization. This process occurs randomly for all of the cells in the organism's body. Because a given female's two X chromosomes will almost certainly differ in their specific pattern of alleles, this will result in differing cell phenotypes depending on which chromosome is silenced. Calico cats, which are almost all female, [20] demonstrate one of the most commonly observed manifestations of this process. [21]

Trinucleotide repeat disorders Edit

Trinucleotide repeat disorders also follow a non-Mendelian pattern of inheritance. These diseases are all caused by the expansion of microsatellite tandem repeats consisting of a stretch of three nucleotides. [22] Typically in individuals, the number of repeated units is relatively low. With each successive generation, there is a chance that the number of repeats will expand. As this occurs, progeny can progress to premutation and ultimately affected status. Individuals with a number of repeats that falls in the premutation range have a good chance of having affected children. Those who progress to affected status will exhibit symptoms of their particular disease. Prominent trinucleotide repeat disorders include Fragile X syndrome and Huntington's disease. In the case of Fragile X syndrome it is thought that the symptoms result from the increased methylation and accompanying reduced expression of the fragile X mental retardation gene in individuals with a sufficient number of repeats. [23]