Materials for practical class 4

PECULIARITIES OF HUMAN GENETICS. BASIC PATTERNS OF INHERITANCE (MONOHYBRID, DIHYBRID  AND POLYHYBRID CROSS). MULTIPLE ALLELES. GENETICS OF BLOOD GROUPS. GENES INTERACTION. PLEIOTROPY.

 

After many centuries of speculation about heredity, the puzzle was finally solved in the space of a few generations. Guided by the work of Mendel and a generation of investigators determined to explain his results, the basic outline of how heredity works soon became clear. Hereditary traits are specified by genes, which are integral parts of chromosomes. The movements of chromosomes during meiosis produce the patterns of segregation and independent assortment that Mendel reported. Two of the most important discoveries made after Mendel were that (1) chromosomes exchange genes during meiosis and (2) genes located far apart on chromosomes are more likely to have an exchange occur between them. These findings allowed investigators to learn how genes were distributed on chromosomes long before we knew how to isolate them.

This core of knowledge, this basic outline of heredity, has led to a long chain of investigation and questions. Is human heredity like that of a garden pea? What is the physical nature of a gene? How do genes change, and why? How does a difference in a gene produce a difference in a phenotype? The people who ask such questions are called geneticists, and the body of what they have learned and are learning is called genetics. Genetics is one of the most active subdisciplines of biology.

 

Genetics a discipline of biology, is the science of genes, heredity, and variation in living organisms.

Genetics is the process of trait inheritance from parents to offspring, including the molecular structure and function of genes, gene behavior in the context of acell or organism (e.g. dominance and epigenetics), gene distribution, and variation and change in populations. Given that genes are universal to living organisms, genetics can be applied to the study of all living systems, including bacteria, plants, animals, and humans. The observation that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. The modern science of genetics, seeking to understand this process, began with the work of Gregor Mendel in the mid-19th century.

Mendel observed that organisms inherit traits by way of discrete “units of inheritance”. This term, still used today, is a somewhat ambiguous definition of agene. A more modern working definition of a gene is a portion (or sequence) of DNA that codes for a known cellular function. This portion of DNA is variable, it may be small or large, have a few subregions or many subregions. The word “Gene” refers to portions of DNA that are required for a single cellular process or single function, more than the word refers to a single tangible item. A quick idiom that is often used (but not always true) is “one gene, one protein” meaning a singular gene codes for a singular protein type in a cell. Another analogy is that a “gene” is like a “sentence” and “nucleotides” are like “letters”. A series of nucleotides can be put together without forming a gene (non-coding regions of DNA), like a string of letters can be put together without forming a sentence (babble). Nonetheless, all sentences must have letters, like all genes must have nucleotides.

The sequence of nucleotides in a gene is read and translated by a cell to produce a chain of amino acids which in turn spontaneously folds into a protein. The order of amino acids in a protein corresponds to the order of nucleotides in the gene. This relationship betweeucleotide sequence and amino acid sequence is known as the genetic code. The amino acids in a protein determine how it folds into its unique three-dimensional shape, a structure that is ultimately responsible for the proteins function. Proteins carry out many of the functions needed for cells to live. A change to the DNA in a gene can change a protein’s amino acid sequence, thereby changing its shape and function, rendering the protein ineffective or even malignant. When a gene change occurs, it is referred to as a mutation.

Genetics acts in combination with an organism’s environment and experiences to influence development and behavior. Genes may be activated or inactivated, as determined by a cell’s or organism’s intra- or extra-cellular environment. For example, while genes play a role in determining human height, an individual’s nutrition and health during childhood also have a large effect.

         In diploid organisms each body cell (or ‘somatic cell’) contains two copies of the genome. So each somatic cell contains two copies of each chromosome, and two copies of each gene. The exceptions to this rule are the sex chromosomes that determine sex in a given species. For example, in the XY system that is found in most mammals – including human beings – males have one X chromosome and one Y chromosome (XY) and females have two X chromosomes (XX). The paired chromosomes that are not involved in sex determination are called autosomes, to distinguish them from the sex chromosomes. Human beings have 46 chromosomes: 22 pairs of autosomes and one pair of sex chromosomes (X and Y).

The different forms of a gene that are found at a specific point (or locus) along a given chromosome are known as alleles. Diploid organisms have two alleles for each autosomal gene – one inherited from the mother, one inherited from the father.

Mendelian inheritance patterns

Within a population, there may be a number of alleles for a given gene. Individuals that have two copies of the same allele are referred to as homozygous for that allele; individuals that have copies of different alleles are known as heterozygous for that allele. The inheritance patterns observed will depend on whether the allele is found on an autosomal chromosome or a sex chromosome, and on whether the allele is dominant or recessive.

Autosomal dominant

If the phenotype associated with a given version of a gene is observed when an individual has only one copy, the allele is said to be autosomal dominant. The phenotype will be observed whether the individual has one copy of the allele (is heterozygous) or has two copies of the allele (is homozygous).

Autosomal recessive

If the phenotype associated with a given version of a gene is observed only when an individual has two copies, the allele is said to be autosomal recessive. The phenotype will be observed only when the individual is homozygous for the allele concerned. An individual with only one copy of the allele will not show the phenotype, but will be able to pass the allele on to subsequent generations. As a result, an individual heterozygous for an autosomal recessive allele is known as a carrier.

 

Sex-linked or X-linked inheritance

In many organisms, the determination of sex involves a pair of chromosomes that differ in length and genetic content – for example, the XY system used in human beings and other mammals.

The X chromosome carries hundreds of genes, and many of these are not connected with the determination of sex. The smaller Y chromosome contains a number of genes responsible for the initiation and maintenance of maleness, but it lacks copies of most of the genes that are found on the X chromosome. As a result, the genes located on the X chromosome display a characteristic pattern of inheritance referred to as sex-linkage or X-linkage.

Females (XX) have two copies of each gene on the X chromosome, so they can be heterozygous or homozygous for a given allele. However, males (XY) will express all the alleles present on the single X chromosome that they receive from their mother, and concepts such as ‘dominant’ or ‘recessive’ are irrelevant.

A number of medical conditions in humans are associated with genes on the X chromosome, including haemophilia, muscular dystrophy and some forms of colour blindness.

 

Non-Mendelian inheritance patterns

Complex and multifactorial inheritance

Some traits or characteristics display continuous variation, a range of phenotypes that cannot be easily divided into clear categories. In many of these cases, the final phenotype is the result of an interaction between genetic factors and environmental influences.

An example is human height and weight. A number of genetic factors within the individual may predispose them to fall within a certain height or weight range, but the observed height or weight will depend on interactions between genes, and between genes and environmental factors (for example, nutrition). Traits in which a range of phenotypes can be produced by gene interactions and gene-environment interactions are known as complex ormultifactorial.

Mitochondrial inheritance

Animal and plant cells contain mitochondria that have their evolutionary origins in protobacteria that entered into a symbiotic relationship with the cells billions of years ago. The chloroplasts in plant cells are also the descendants of symbiotic protobacteria. As a result, mitochondria and chloroplasts contain their own DNA.

Mitochondria are scattered throughout the cytoplasm of animal and plant cells, and their DNA is replicated as part of the process of mitochondrial division. A newly formed embryo receives all its mitochondria from the mother through the egg cell, so mitochondrial inheritance is through the maternal line.

Genomic imprinting

The expression of a small number of human genes is influenced by whether the gene has been inherited from the mother or father. This process – called genomic (or parental) imprinting – usually means that the organism expresses one of its alleles but not both. In many cases the non-expressed allele is inactivated – for example, by DNA methylation. (High levels of DNA methylation are known to inhibit gene activity.)

Imprinting involves three stages:

·                     the inactivation of an allele in the ovaries or testes before or during the formation of egg cells or sperm

·                     the maintenance of that inactivation in the somatic cells of the offspring organism

·                     the removal, then re-establishment, of the inactivation during the formation of egg cells or sperm in the offspring organism

The pattern of imprinting is maintained in the somatic cells of the organism but can alter from generation to generation.

 

 

The basic laws of inheritance are important in understanding patterns of disease transmission. The inheritance patterns of single gene diseases are often referred to as Mendelian since Gregor Mendel first observed the different patterns of gene segregation for selected traits in garden peas and was able to determine probabilities of recurrence of a trait for subsequent generations. If a family is affected by a disease, an accurate family history will be important to establish a pattern of transmission. In addition, a family history can even help to exclude genetic diseases, particularly for common diseases where behavior and environment play strong roles.

Most genes have one or more versions due to mutations or polymorphisms referred to as alleles. Individuals may carry a ‘normal’ allele and/or a ‘disease’ or ‘rare’ allele depending on the impact of the mutation/polymorphism (e.g., disease or neutral) and the population frequency of the allele. Single-gene diseases are usually inherited in one of several patterns depending on the location of the gene and whether one or two normal copies of the gene are needed for the disease phenotype to manifest.

The expression of the mutated allele with respect to the normal allele can be characterized as dominant, co-dominant, or recessive. There are five basic modes of inheritance for single-gene diseases: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial.

Genetic heterogeneity is a common phenomenon with both single-gene diseases and complex multi-factorial diseases. It should not be surprising that multiple affected family members may experience different levels of disease severity and outcomes. This effect may be due to other genes influencing the disease phenotype or different mutations in the same gene resulting in similar, but not identical phenotypes. 

 

EARLY IDEAS ABOUT HEREDITY: THE ROAD TO MENDEL

 Like many great puzzles, the riddle of heredity seems simple now that it has been solved. The solution was not an easy one to find, however. Our present understanding is the result of a long history of thought, surmise, and investigation. At every stage we have learned more, and as we have done so, the models used to describe the mechanisms of heredity have been changed to encompass new facts.

Two concepts provided the basis for most of the thinking about heredity before the twentieth century:

1. Heredity occurs within species. For a very long time people believed that it was possible to obtain bizarre composite animals by breeding (crossing) widely different species. The Minotaur of Cretan mythology, a creature with the body of a bull and the torso and head of a man, is one example. The giraffe was thought to be another; its scientific name, Giraffa Camelopardalis, suggests that it was believed to be the result of a cross between a camel and a leopard. From the Middle Ages onward, however, people discovered that such extreme crosses were not possible and that variation and heredity occur mainly within the boundaries of a particular species. Species were thought to have been maintained without significant change from the time of their creation.

2. Traits are transmitted directly. When variation is inherited by offspring from their parents, what is transmitted? The ancient Greeks suggested that parts of the bodies of parents were transmitted directly to their offspring. Reproductive material, which Hippocrates called gonos, meaning “seed,” was thought to be contributed by all parts of the body; hence a characteristic such as a misshapen limb was transmitted directly to the offspring by elements that came from the misshapen limb of the parent. Information from each part of the body was thought to be passed along independently of the information from the other parts, and the child was formed after hereditary material from all parts of the parents’ bodies had come together.

This idea was predominant until fairly recently. For example, in 1868 Charles Darwin proposed that all cells and tissues excrete microscopic granules, or “gem mules,” that are passed along to offspring, guiding the growth of the corresponding part in the developing embryo. Most similar theories of the direct transmission of hereditary material assumed that the male and female contributions blended in the offspring. Thus parents with red and brown hair would be expected to produce children with reddish brown hair, and tall and short parents would produce children of intermediate height.

Taken together, however, these two concepts lead to a paradox. If no variation enters a species from outside, and if the variation within each species is blended in every generation, then all members within a species should soon resemble one another exactly. This does not happen, however. Individuals within most species differ widely from one another, and they differ in characteristics that are transmitted from generation to generation.

How can this paradox be resolved? Actually, the resolution had been provided long before Darwin, in the work of the German botanist Josef Koelreuter. In 1760 Koelreuter carried out the first successful hybridizations of plant species. He was able to cross different species of tobacco and obtain fertile offspring. The hybrids differed in appearance from both of their parent strains. When crosses were made within the hybrid generation, the offspring were highly variable. Some of these offspring resembled plants of the hybrid generation, and a few resembled not the hybrid generation, but rather the original parent strains (that is, the grandparents of these individuals).

Koelreuter’s work provided an important clue about how heredity works: the traits that he was studying were capable of being masked in one generation, only to reappear in the next. This pattern is not predicted by the theory of direct transmission. How could a characteristic that is transmitted directly be latent and then reappear? Nor were Koelreuter’s traits “blended.” A contemporary account records that they reappeared in the next generation “fully restored to all their original powers and properties “

It is important to note that the offspring of Koelreuter’s crosses were not identical to one another. Some resembled the parents of the crosses, whereas others did not; the alternative forms of the traits Koelreuter was studying were distributing themselves among the offspring. A modern geneticist would say the alternative forms of a trait were segregating among the progeny of a single mating, meaning that some offspring exhibit one alternative form of a trait (for example, hairy leaves), whereas other offspring from the same mating exhibit a different alternative (smooth leaves). This segregation of alternative forms of a trait provided the clue that led Mendel to his understanding of the nature of heredity.

Over the next hundred years, Koelreuter’s work was elaborated on by other investigators. Prominent among them were English gentleman farmers who were trying to improve varieties of agricultural plants. In one such series of experiments, carried out in the 1790s, T. A. Knight crossed two true-breeding varieties (varieties that were uniform from one generation to the next) of the garden pea, Pisum sativum. One of these varieties had purple flowers; the other, white flowers. All of the progeny of the cross had purple flowers. Among the offspring of these hybrids, however, were some plants with purple flowers and others, less common, with white ones. Just as in Koelreuter’s earlier studies, a character trait from one of the parents was hidden in one generation, only to reappear in the next.

 

Early geneticists demonstrated that (1) some forms of an inherited trait can be masked in some generations but may subsequently reappear unchanged in future generations, (2) forms of a trait segregate among the offspring of a cross, and (3) some forms of a trait are more likely to be represented than their alternatives.

 

In these deceptively simple results were the makings of a scientific revolution. Another century passed, however, before the process of segregation of genes was appreciated properly. Why did it take so long? One reason was that early workers did not quantify their results. A numerical record of results proved to be crucial to the understanding of this process. Knight and later experimenters who carried out other crosses with pea plants noted that some traits had a “stronger tendency” to appear than others, but they did not record the numbers of the different classes of progeny. Science was young then, and it was not obvious that the numbers were important.

 

MENDEL AND THE GARDEN PEA

The first quantitative studies of inheritance were carried out by Gregor Mendel, an Austrian monk. Born in 1822 to peasant parents, Mendel was educated in a monastery and went on to study science and mathematics at the University of Vienna, where he failed his examinations for a teaching certificate. Returning to the monastery (where he spent the rest of his life, eventually becoming abbot), Mendel initiated a series of experiments on plant hybridization in its garden. The results of these experiments would ultimately change our views of heredity irrevocably.

 For his experiments Mendel chose the garden pea, the same plant that Knight and many others had studied earlier. The choice was a good one for several reasons:

1. Because many earlier investigators had produced hybrid peas by crossing different varieties, Mendel knew that he could expect to observe segregation among the offspring.

2. A large number of true-breeding varieties of peas were available. Mendel initially examined 32. Then, for further study, he selected lines that differed with respect to seven easily distinguishable traits, such as smooth versus wrinkled seeds (Figure 48) and purple versus white flowers (a characteristic that Knight had studied 60 years earlier).

3. Pea plants are small, are easy to grow, and have a short generation time. Thus one can conduct experiments involving numerous plants, grow several generations in a single year, and obtain results relatively quickly.

4. The sexual organs of the pea are enclosed within the flower. The flowers of peas, like those of most flowering plants, contain both male and female sex organs. Furthermore, the gametes produced by the male and female parts of the same flower, unlike those of many flowering plants, can fuse to form a viable offspring. Fertilization takes place automatically within an individual flower if it is not disturbed. As a result of this process, the offspring of garden peas are the progeny of a single individual. Therefore one can either let self-fertilization take place within an individual flower or remove its male parts before fertilization, introduce pollen from a strain with alternative characteristics, and thus perform an experimental cross.

 

MENDEL’S EXPERIMENTAL DESIGN

 Mendel usually conducted his experiments in three stages:

1 He first allowed pea plants of a given variety to produce progeny by self-fertilization for several generations. Mendel was thus able to assure himself that the forms of traits that he was studying were indeed constant, transmitted regularly from generation to generation. Pea plants with white flowers, for example, when crossed with each other, produced only offspring with white flowers, regardless of the number of generations for which the experiment was continued.

2. Mendel then conducted crosses between varieties exhibiting alternative forms of traits. For example, he removed the male parts from a flower of a plant that produced white flowers and fertilized it with pollen from a purple-flowered plant. He also carried out the reciprocal cross, by reversing the procedure, using pollen from a white-flowered individual to fertilize a flower on a pea plant that produced purple flowers.

3. Finally, Mendel permitted the “hybrid” offspring produced by these crosses to self-pollinate for several generations. By doing so, he allowed the alternative forms of a trait to segregate among the progeny. This was the same experimental design that Knight and others had used much earlier. But Mendel added a new element: he counted the numbers of offspring of each type and in each succeeding generation. No one had ever done that before. The quantitative results that Mendel obtained proved to be of supreme importance in helping him (and us) understand the process of heredity.

WHAT MENDEL FOUND

 

 When Mendel crossed two contrasting varieties, such as purple-flowered plants with white-flowered plants, the hybrid offspring that he obtained were not intermediate in flower color, as the theory of blending inheritance would have predicted. Instead, the hybrid offspring in every case resembled one of their parents. It is customary to refer to these hybrid offspring as the first filial, or F₁ generation. Thus in a cross of white-flowered with purple-flowered plants the F₁ offspring all had purple flowers, just as Knight and others had reported earlier. Mendel referred to the trait that was expressed in the F₁ plants as dominant and to the alternative form, which was not expressed in the F_1` plants, as recessive. For each of the seven pairs of contrasting forms of traits that Mendel examined, one of the pair proved to be dominant; the other, recessive.

After individual F₁ plants had been allowed to mature and self-pollinate, Mendel collected and planted the fertilized seed from each plant to see what the offspring in this second filial, or F₂, generation would look like. He found, just as Knight had earlier, that some of the F₂ plants exhibited the recessive form of the trait. Latent in the F₁ generation, the recessive alternative reappeared among some of the F₂ individuals.

At this stage Mendel instituted his radical change in experimental design. He counted the numbers of each type among the F₂ progeny. Mendel was investigating whether the proportions of the F₂ types would provide some clue about the mechanism of heredity. For example, he scored a total of 929 F₂ individuals in the cross between the purple-flowered F₁ plants described above. Of these F₂ plants, 705 had purple flowers and 224 had white flowers. Almost precisely one fourth of the F₂ individuals (24.1 %) exhibited white flowers, the recessive trait.

Mendel examined seven traits with contrasting alternative forms, and the numerical result was always the same: three fourths of the F₂ individuals exhibited the dominant form of the trait, and one fourth displayed the recessive form of the trait. The dominant/recessive ratio among the F₂ plants was always 3:1.

Mendel went on to examine how the F₂ plants behaved in subsequent generations. He found that the recessive one fourth were always true-breeding. In the cross of white-flowered with purple-flowered plants, for example, the white-flowered F₂ individuals reliably produced white-flowered offspring when they were allowed to self-fertilize. By contrast, only one third of the dominant purple-flowered F₂ individuals (one fourth of the total offspring) proved true-breeding, whereas two thirds were not. This last class of plants produced dominant and recessive F₃ individuals in a ratio of 3:1. This result suggested that, for the entire sample, the 3:1 ratio that Mendel observed in the F₂ generation was really a disguised 1:2:1 ratio: one fourth pure-breeding dominant individuals to one half not-pure-breeding dominant individuals to one fourth pure-breeding recessive individuals.

 

HOW MENDEL INTERPRETED HIS RESULTS

 From these experiments Mendel was able to understand four things about the nature of heredity. First, plants exhibiting the traits he studied did not produce progeny of intermediate appearance when crossed, as a theory of blending inheritance would have predicted. Instead, alternatives were inherited intact, as discrete characteristics that either were or were not seen in a particular generation. Second, for each pair of traits that Mendel examined, one alternative was not expressed in the F₁ hybrids, although it reappeared in some F₂ individuals. The “invisible ” trait must therefore have been latent (present but not expressed) in the F₁ individuals. Third, the pairs of alternative forms of the traits that Mendel examined segregated among the progeny of a particular cross, some individuals exhibiting one form of a trait, some the other. Fourth, pairs of alternatives were expressed in the F₂ generation in the ratio of three-fourths dominant to one-fourth recessive. This characteristic 3:1 segregation is often referred to as the Mendelian ratio.

To explain these results, Mendel proposed a simple model. It has become one of the most famous models in the history of science, containing simple assumptions and making clear predictions. The model has five elements. For each, we will first state Mendel’s assumption and then rephrase it in modern terms.

1. Parents do not transmit their physiological traits or form directly to their offspring. Rather, they transmit discrete information about the traits, what Mendel called “factors.” These factors later act in the offspring to produce the trait. In modern terms we would say that the forms of traits that an individual will express are encoded by the factors (genes) that it receives from its parents.

2. Each individual, with respect to each trait, contains two factors, which may code for the same form of the trait or which may code for two alternative forms of the trait. We now know that there are two factors for each trait present in each individual because these factors are carried on chromosomes, and each adult individual is diploid. When the individual forms gametes (eggs or sperm), only one of each kind of chromosome is included in each gamete: it is haploid. Therefore only one factor for each trait of the adult organism is included in the gamete. Which of the two factors for each trait is included in a particular gamete is random.

3. Not all copies of a factor are identical. The alternative forms of a factor, leading to alternative forms of a trait, are called alleles. When two haploid gametes containing exactly the same allele of a factor fuse during fertilization, the offspring that develops from that zygote is said to be homozygous; when the two haploid gametes contain different alleles, the individual offspring is heterozygous.

In modern terminology Mendel’s factors are called genes. We now know that one of Mendel’s “factors,” a gene, is composed of a DNA nucleotide sequence. The position on a chromosome where a gene is located is often referred to as a locus. Most genes exist in alternative versions, or alleles, with differences at one or more nucleotide positions in the DNA. Different alleles of a gene are usually recognized by the change in appearance or function that results from the nucleotide differences.

4. The two alleles, one each contributed by the male and female gametes, do not influence each other in any way. In the cells that develop within the new individual these alleles remain discrete (Mendel referred to them as “uncontaminated”). They neither blend with one another nor become altered in any other way. Thus when this individual matures and produces its own gametes, the alleles for each gene are segregated randomly into these gametes, just as described in point 2.

5. The presence of a particular element does not ensure that the form of the trait encoded by it will actually be expressed in the individual carrying that allele. In heterozygous individuals only one (dominant) allele achieves expression, the other (recessive) allele being present but unexpressed. In modern terms each element encodes the information that specifies an alternative form of a trait, rather than containing the trait itself. The presence of information does not guarantee its expression, as any undergraduate student taking an examination appreciates. To distinguish between the presence of an element and its expression, modern geneticists refer to the totality of alleles that an individual contains as the genotype and to the physical appearance of an individual as the phenotype. The phenotype of an individual is the observable outward manifestation of the genes that it carries. The phenotype is the end result of the functioning of the enzymes and proteins encoded by the genes of the individual, its genotype. The genotype is the blueprint; the phenotype is the realized outcome.

Mendel’s results were clear because he was studying alternatives that exhibited complete dominance. Many traits in humans also exhibit dominant or recessive inheritance, in a manner similar to the traits Mendel studied in peas.

The genes which an individual has are referred to as its genotype; the outward appearance of the individual is referred to as its phenotype.

These five elements, taken together, constitute Mendel’s “model” of the hereditary process. Does Mendel’s model predict the result that he actually obtained?

THE TESTCROSS

 

To test his model further, Mendel devised a simple and powerful procedure called the testcross. Consider a purple-flowered individual: is it homozygous or heterozygous? It is impossible to tell simply by looking at its phenotype. To learn its genotype, you must cross it with some other plant. With what kind of plant? If you cross it with a homozygous dominant individual, all of the progeny will show the dominant phenotype whether the test plant is homozygous or heterozygous. It is also difficult (but not impossible) to distinguish between the two possible test plant genotypes by crossing with a heterozygous individual. If you cross the test individual with a homozygous recessive individual, however, the two possible test plant genotypes give totally different results (Figure 49):

Alternative 1: unknown individual homozygous

WW x ww: all offspring have purple flowers (Ww)

Alternative 2: unknown individual heterozygous

Ww x ww: one half of offspring have white flowers (ww) and one half has purple flowers (Ww)

To perform his test cross, Mendel crossed heterozygous F₁ individuals back to the parent homozygous for the recessive trait. He predicted that the dominant and recessive traits would appear in a 1:1 ratio.

For each pair of alleles he investigated, Mendel observed phenotypic testcross ratios very close to 1:1, just as his model predicted.

Mendel’s model thus accounted in a neat and satisfying way for the segregation ratios that he had observed. Its central assumption – that alternative alleles segregate from one another in heterozygous individuals and remain distinct – has since been verified in countless other organisms. It is commonly referred to as Mendel’s Law of Heredity, or the Law of Segregation. As you see, the segregational behavior of alternative alleles has a simple physical basis, one that was unknown to Mendel. It is a tribute to the intellectual power of Mendel’s analysis that he arrived at the correct scheme with no knowledge of the cellular mechanisms of inheritance: neither chromosomes nor meiosis had yet been described.

Mendel’s original paper describing his experiments, published in 1866, remains charming and interesting to read. His explanations are clear, and the logic of his arguments is presented in lucid detail. Unfortunately, Mendel failed to arouse much interest in his findings, which were published in the journal of the local natural history society. Only 115 copies of the journal were sent out, in addition to 40 reprints, which Mendel distributed himself. Only the German botanist Carl Naegeli was interested enough to correspond with Mendel about his findings. Naegeli believed that Mendel was wrong; he was convinced that the offspring of all hybrids must be variable. Although Mendel’s results did not receive much notice during his lifetime, in 1900,16 years after his death, three different investigators independently rediscovered his pioneering paper. They came across it while searching the literature in preparation for publishing their own findings, which were very similar to those Mendel had quietly presented more than three decades earlier.

Mendel’s Law states that (1) the alternative forms of a trait encoded by a gene are specified by alternative alleles of that gene and are discrete (do not blend in heterozygotes); (2) when gametes are formed in heterozygous diploid individuals, the two alternative alleles segregate from one another; and (3) each gamete has an equal probability of possessing either member of an allele pair.

 

INDEPENDENT ASSORTMENT

After Mendel had demonstrated that different alleles of a given gene segregate independently of one another in crosses, he asked whether different genes also segregated independently of one another. Would the possession of a particular allele for one trait (say seed shape) influence which allele the gamete had for another trait (say color)?

Mendel set out to answer this question in a straightforward way. He first established a series of pure-breeding lines of peas that differed from one another with respect to two of the seven pairs of characteristics that he had studied. His second step was to cross contrasting pairs of the pure-breeding lines. In a cross involving different seed shape alleles (round, W, and wrinkled, w) and different seed color alleles (yellow, G, and green, g), all the F₁ individuals were identical, each being heterozygous for both seed shape (Ww) and seed color (Gg). The F₁ individuals of such a cross are dihybrid individuals. A dihybrid is an individual heterozygous for two genes.

The third step in Mendel’s analysis was to allow the dihybrid individuals to self-fertilize. If the segregation of alleles affecting seed shape were independent of the segregation of those affecting seed color, then the probability that a particular pair of seed shape alleles would occur together with a particular pair of seed color alleles would be simply the product of the individual probabilities that each pair would occur separately. Thus the probability that an individual with wrinkled, green seeds would appear in the F₂ generation would be equal to the probability of observing an individual with wrinkled seeds (one fourth) times the probability of observing an individual with green seeds (one fourth), or one sixteenth.

Since the genes concerned with seed shape and those concerned with seed color are each represented by a pair of alternative alleles in the dihybrid individuals, four types of gametes are expected: WG, Wg, wG, wg. Thus in the F₂ generation there are 16 possible combinations of alleles, each of them equally probable. Of the 16 combinations, 9 possess at least one dominant allele for each gene (usually signified W–G–, where the dash indicates the presence of either allele and thus should have round, yellow seeds. Three possess at least one dominant W allele but are homozygous recessive for color (W-gg), three others possess at least one dominant G allele but are homozygous recessive for shape (wwG-), and one combination among the 16 is homozygous recessive for both genes (wwgg). The hypothesis that color and shape genes assort independently thus predicts that the F₂ generation of this dihybrid cross will display a ratio of 9 individuals with round, yellow seeds to 3 individuals with round, green seeds to 3 individuals with wrinkled, yellow seeds to 1 with wrinkled, green seeds: a 9:3:3:1 ratio.

What did Mendel actually observe? He examined a total of 556 seeds from dihybrid plants that had been allowed to self-fertilize, and he obtained the following results:

315        Round, yellow           W-G-

108        Round, green             W-gg

101        Wrinkled, yellow        wwG-

32        Wrinkled, green          wwgg

This is very close to a perfect 9:3:3:1 ratio (313:104:104:35). Thus the two genes appeared to assort completely independently of one another. Note that this independent assortment of different genes io way alters the independent segregation of individual pairs of alleles. Round and wrinkled seeds occur approximately in a ratio of 3:1 (423:133), as do yellow and green seeds (416:140). Mendel obtained similar results for other pairs of traits.

 

Mendel’s observation is often referred to as Mendel’s Law of Heredity, or the Law of Independent Assortment. Genes that assort independently of one another, as did Mendel’s seven genes, usually do so because the genes are located on different chromosomes, which segregate from one another during the meiotic process of gamete formation. A modern restatement of Mendel’s Second Law would be that genes that are located on different chromosomes assort independently during meiosis.

Mendel’s Law of Heredity states that genes located on different chromosomes assort independently of one another.

 

A VOCABULARY OF GENETICS

         allele One of two or more alternative states of a gene.

diploid Having two sets of chromosomes, referred to as homologues. Animals, the dominant phase in the life cycle of most plants, and some protists are diploid.

dominant allele An allele that dictates the appearance of heterozygotes. One allele is said to be dominant over another if in individual heterozygous for that allele has the same appearance as an individual homozygous for it.

gene The basic unit of heredity. A sequence of DNA nucleotides on a chromosome that encodes a polypeptide or RNA molecule, and so determines the nature of an individual’s inherited traits.

genotype The total set of genes present in the cells of an organism. This term is often also used to refer to the set of allele at a single gene locus.

haploid Having only one set of chromosomes. Gametes, certain protists and fungi, and certain stages in the life cycle of plants are haploid.

heterozygote A diploid individual carrying two different alleles of a gene on its two homologous chromosomes. Most human beings are heterozygous for many genes.

homozygote A diploid individual whose two copies of a gene are the same. An individual carrying identical alleles on both homologous chromosomes is said to be homozygous for the gene.

locus The location of a gene on a chromosome.

phenotype The realized expression of the genotype. The phenotype is the observable expression of a trait (affecting an individual’s structure, physiology, or behavior) that results from the biological activity of the DNA molecules.

recessive allele An allele whose phenotypic effect is masked in heterozygotes by the presence of dominant allele.  

 

FROM GENOTYPE TO PHENOTYPE: HOW GENES INTERACT

It is important to keep in mind that the “gene” of Mendelian genetics is an abstract concept used to refer to elements located on the chromosomes. These elements act in some unspecified way to produce differences among the progeny. We can see these differences and study their ratios. Whatever the gene’s physical basis, however, an investigator must realize that the relationship between the chromosomal gene and the phenotype that the investigator studies is not always a simple one; Mendel was lucky in his choice of traits. Often genes reveal more complex patterns, including the following:

 

Multiple alleles. Although a diploid individual may possess no more than two alleles at one time, this does not mean that only two allele alternatives are possible for a given gene in the entire population. On the contrary, almost all genes that have been studied exhibit several different alleles. The gene that determines the human ABO blood group, for example, has three common alleles.

 

Gene interaction. Few phenotypes are the result of the action of only one gene. Most traits reflect the action of many genes that act sequentially or jointly. When genes act sequentially, as in a biochemical pathway, an allele specifying a defective enzyme early in the pathway blocks the flow of material through the pathway and thus makes it impossible to judge whether the later steps of the pathway are functioning properly. Such interactions between genes are the basis of the phenomenon called epistasis.

 

Epistasis is an interaction between the products of two genes in which one of them modifies the phenotypic expression produced by the other. Thus in a two-step biochemical pathway where the gene governing the second step has two alleles yielding black (dominant) or blonde (recessive) hair it is impossible to deduce which of these two alleles is present in individuals whose alleles in the first step are nonfunctional – the hair is white, whatever the alleles governing step two. Epistatic interactions between genes often make the interpretation of particular phenotypes very difficult.

 

Continuous variation. When multiple genes act jointly to determine a trait such as height or weight, the contribution caused by the segregation of one particular gene is difficult to monitor, just as it is difficult to follow the flight of one bee within a swarm. Because all of the genes that play a role in determining the phenotype are segregating independently of one another, one sees a gradation in degree of difference when many individuals are examined.

 

Pleiotropy. Often an individual allele will have more than one effect on the phenotype. Such an allele is said to be pleiotropic. Thus, when the pioneering French geneticist Lucien Cuenot studied yellow fur in mice, a dominant trait, he was unable to obtain a true-breeding homozygous yellow strain by crossing individual yellow mice with one another – individuals that were homozygous for the yellow allele died. The yellow allele was pleiotropic: one effect was yellow color; another effect was a lethal developmental defect. Thus a pleiotropic gene alteration may be dominant with respect to one phenotypic consequence (yellow fur) and recessive with respect to another (lethal developmental defect). Pleiotropic relationships occur because in examining the characteristics of organisms, we are studying the consequences of the action of products made by genes. These products often also perform other functions about which we are ignorant.

 

Incomplete dominance. Not all alternative alleles are fully dominant or recessive in heterozygotes. Sometimes heterozygous individuals do not resemble one parent precisely. Some pairs of alleles produce instead a heterozygous phenotype that is intermediate between the parents (intermediate or incomplete dominance), resembles one allele closely but can be distinguished from it (partial dominance), or is one in which both parental phenotypes can be distinguished in the heterozygote (codominance).

 

Environmental effects. The degree to which many alleles are expressed depends on the environment. Some alleles encode an enzyme whose activity is more sensitive to conditions such as heat or light than are other alleles.

 

Modified Mendelian Ratios

 When individuals heterozygous for two different genes mate (a dihybrid cross), four different phenotypes are possible among the progeny: the dominant phenotype of both genes is displayed, one of the dominant phenotypes is displayed, or neither dominant phenotype is displayed. Mendelian assortment predicts that these four possibilities will occur in the proportions 9:3:3:1. Sometimes, however, it is not possible for an investigator to successfully identify each of the four possible phenotypic classes, because two or more of the classes look alike.

One example of such difficulty in identification is seen in analysis of particular varieties of corn, Zea mays. Some commercial varieties exhibit a purple pigment called anthocyanin in their seed coats, whereas others do not. When in 1918 the geneticist R. A. Emerson crossed two pure-breeding corn varieties, neither of which typically exhibits any anthocyanin pigment, he obtained a surprising result: all of the F₁ plants produced purple seeds. The two white varieties, which had never been observed to make pigment, would, when crossed, produce progeny that uniformly make the pigment.

When two of these pigment-producing F₁ plants were crossed to produce an F₂ generation, 56% were pigment producers and 44% were not. What was happening? Emerson correctly deduced that two genes were involved in the pigment-producing process and that the second cross had thus been a dihybrid cross such as described by Mendel. Mendel predicted 16 possible genotypes in equal proportions (9 + 3 + 3 + 1 = 16) suggesting to Emerson that the total number of genotypes in his experiment was also 16. How many of these were in each of the two types Emerson obtained? He multiplied the fraction that were pigment producers (.56) X 16 = 9, and multiplied the fraction that were not (.44) X 16 = 7. Thus Emerson had in fact a modified ratio of 9:7 instead of the usual 9:3:3:1 ratio.

In this case the pigment anthocyanin is produced from a colorless molecule by two enzymes that work one after the other. In other words the pigment is the product of a two-step biochemical pathway: starting molecule (colorless), than intermediate (colorless) and than anthocyanin (purple).

For pigment to be produced, a plant must possess at least one good copy of each enzyme. The dominant alleles encode functional enzymes; the recessive alleles, defective nonfunctional ones. Of the 16 genotypes predicted by random assortment, 9 contain at least one dominant allele of both genes – these are the purple progeny. The 9:7 ratio that Emerson observed resulted from the pooling of the three phenotypic classes that lack dominant alleles at either or both loci (3 + 3 + 1=7) and so all looked the same, nonpigmented.

 f your baby or child has been born with one or more extra fingers (polydactyly), we know that you and your family are concerned. So, please know that at Children’s Hospital Boston, we will approach your child’s treatment and care with sensitivity and support—for your child and your whole family.   

If your child has polydactyly, it means that he has extra fingers and/or toes.

Polydactyly is a fairly common congenital defect that often runs in families. At Children’s, it’s the most common congenital hand problem that we see.

If your child has an extra finger, it may occur in any of three places of his hand:

on the small finger side—most common (ulnar)

on the thumb side, also called thumb duplication—less common (radial)

in the middle of the hand—least common (central)

The extra fingers are usually smaller than his other fingers and are abnormally developed.

Your child’s extra finger can be made up of:

skin and soft tissue (most easily removed)

skin, soft tissue and bone (no joint—more challenging to remove/remodel)

skin, soft tissue and bone with joint (closer to a fully-formed finger—most challenging to remove/remodel)

Polydactyly can sometimes be detected by prenatal ultrasound, and is apparent at birth; the underlying structure of the finger and the course for treatment are determined with x-ray.

In the United States, polydactyly occurs in one out of 500 to 1,000 newborns. Boys and girls are affected about equally.

African-American children are more likely to have polydactyly of on the little finger side; Asians and Caucasians, on the thumb side.

Most forms of polydactyly are treated surgically. Surgery is usually done when the child is between 1 and 2 years old and can range from fairly simple to highly complex. Some mild cases can be treated non-surgically.

MULTIPLE ALLELES

It is important to understand that a gene may exhibit more than two alleles in a population. Mendel deliberately limited his study to pairs of contrasting traits in pea plants; his plants were either tall or short, their flowers purple or white. Similarly, Morgan’s Drosophila had eyes that were either white or red (the normal color). Many human genes also exhibit two alternative alleles. An individual, for example, is either albino or pigmented. It is important to remember, however, that most genes possess more than two possible alleles. Any change in the long sequence of nucleotides that make up a gene is potentially a new allele.

A human gene that typically exhibits more than one allele is the gene that encodes an enzyme that adds sugar molecules to lipids on the surface of red blood cells. These sugars act as recognition markers for our immune system and are called cell surface antigens. The gene encoding the enzyme is designated I and possesses three common alleles: (1) allele B, which adds the sugar galactose; (2) allele A, which adds a modified form of the sugar, galactosamine; and (3) allele O, which does not add a sugar.

 

Many genes possess multiple alleles, several of which may be common within populations.

 When an individual is heterozygous for a gene with many possible alleles, which allele is dominant? Often, no one allele is; instead, each allele has its own effect. Thus an individual heterozygous for the A and B alleles of the I gene produces both forms of the enzyme and adds both galactose and galactosamine to the surfaces of this individual’s blood cells; the cells thus possess antigens with both kinds of sugar attached to them.

Because both alleles are expressed simultaneously in heterozygotes, the A and B alleles are said to be codominant. Either A or B alleles are dominant over the O allele, because in heterozygotes the A or B allele leads to sugar addition and the O allele does not.

ABO Blood Groups

Different combinations of the three possible I gene alleles occur in different individuals, because each person possesses two copies of the chromosome bearing the I gene and may be homozygous for any allele or heterozygous for any two. The different combinations of the three alleles produce four different phenotypes:

1. Persons who add only galactosamine are called type A individuals. They are either AA homozygotes or AO heterozygotes.

2. Persons who add only galactose are called type B individuals. They are either BB homozygotes or BO heterozygotes.

3. Persons who add both sugars are called type AB individuals. They are, as we have seen, AB heterozygotes.

4. Persons who add neither sugar are called type O individuals. They are OO homozygotes.

 

The four different cell-surface phenotypes listed above are called the ABO blood groups, or, less commonly, the Landsteiner blood groups, after the man who first described them. As Landsteiner first noted, your immune system can tell the difference between these four phenotypes. If a type A individual receives a transfusion of type B blood, the recipient’s immune system will recognize that the type B blood cells possess a “foreign” antigen (galactose) and attack the donated blood cells. If the donated blood is type AB, this will also happen. However, if the donated blood is type O, no attack will occur, as there are no foreign galactose antigens on the surfaces of blood cells produced by the type O donor. In general, any individual’s immune system will tolerate a transfusion of type O blood. Because neither galactose nor galactosamine is foreign to type AB individuals (they add both to their red blood cells), AB individuals may receive any type of blood.

Some of the ABO blood group phenotypes are more common than others in human populations. In general, type O individuals are the most common, and type AB individuals the least common. Human populations differ from one another a great deal, however. Among North American Indians, for example, the frequency of type A individuals is 31 %, whereas among South American Indians, it is only 4%.

The Rh Blood Group

Another set of cell surface markers on human red blood cells are the Rh blood group antigens, named for the rhesus monkey in which they were first described. About 85% of adult humans have the Rh cell surface marker on their red blood cells, and are called Rh positive (Rh+). Rh negative persons lack this cell surface marker because they are homozygous recessive for the gene encoding it.

If an Rh negative person is exposed to Rh positive blood, the Rh surface antigens of that blood are treated like foreign invaders by the Rh negative person’s immune system, which proceeds to make antibodies directed against the Rh antigens. This most commonly happens when an Rh negative woman gives birth to an Rh positive child (the father being Rh+). Some fetal red blood cells cross the placental barrier and enter the mother’s bloodstream, where they induce the production of “anti-Rh” antibodies, which in later pregnancies can cross back to another fetus and cause its red blood cells to clump, leading to a potentially fatal condition called erythroblastosis fetalis.

SEX LINKAGE

 

 The essential correctness of the chromosomal theory of heredity was demonstrated long before this paradox was resolved. The proof was provided by a single, small fly. In 1910 Thomas Hunt Morgan, studying the fruit fly Drosophila melanogaster, detected a mutant fly, a male fly that differed strikingly from normal flies of the same species. In this fly the eyes were white, instead of the normal red.

Morgan immediately set out to determine if this new trait would be inherited in a Mendelian fashion. He first crossed the mutant male to a normal female to see if red or white eyes were dominant. All F₁ progeny had red eyes, and Morgan therefore concluded that red eye color was dominant over white. Following the experimental procedure that Mendel had established long ago, Morgan then crossed flies from the F₁ generation with each other. Eye color did indeed segregate among the F₂ progeny, as predicted by Mendel’s theory. Of 4252 F₂ progeny that Morgan examined, 782 had white eyes – an imperfect 3:1 ratio, but one that nevertheless provided clear evidence of segregation. Something was strange about Morgan’s result, however, something totally unpredicted by Mendel’s theory: all of the white-eyed F₂ flies were males!

How could this strange result be explained? Perhaps it was not possible to be a white-eyed female fly; such individuals might not be viable for some unknown reason. To test this idea, Morgan testcrossed the F₁ progeny back to the original white-eyed male and obtained white-eyed and red-eyed males and females in a 1:1:1:1 ratio, just as Mendelian theory predicted. So a female could have white eyes. Why then were there no white-eyed females among the progeny of the original cross?

The solution to this puzzle involved sex. In Drosophila the sex of an individual is influenced by the number of copies of a particular chromosome, the X chromosome that an individual possesses. An individual with two X chromosomes is a female, and an individual with only one X chromosome – which pairs in meiosis with a large, dissimilar partner called the Y chromosome – is a male. The female thus produces only X gametes, whereas the male produces both X and Y gametes. When fertilization involves an X sperm, the result is an XX zygote, which develops into a female; when fertilization involves a Y sperm; the result is an XY zygote, which develops into a male.

The solution to Morgan’s puzzle lies in the fact that in Drosophila the white-eye trait resides on the X chromosome and is absent from the Y chromosome. (We now know that the Y chromosome carries almost no functional genes.) A trait that is determined by a factor on the X chromosome is said to be sex-linked. Knowing the white-eye trait to be recessive to the red-eye trait, we caow see that Morgan’s result was a natural consequence of the Mendelian assortment of chromosomes.

Morgan’s experiment is one of the most important in the history of genetics, because it presented the first clear evidence that Sutton was right and that the factors determining Mendelian traits do indeed reside on the chromosomes. The segregation of the white-eye trait, evident in the eye color of the flies, has a one-to-one correspondence with the segregation of the X chromosome, evident from the sexes of the flies.

The white-eye trait behaves exactly as if it was located on an X chromosome, and this is indeed the case. The eye color gene, which specifies eye color in Drosophila, is carried through meiosis as part of an X chromosome. In other words, Mendelian traits such as eye color in Drosophila assort independently because chromosomes do. When Mendel observed the segregation of alternative traits in pea plants, he was observing a reflection of the meiotic segregation of chromosomes.

 

Mendelian traits assort independently because they are determined by genes located on chromosomes that assort independently in meiosis.

 

Many times a trait is determined by more than one gene. Each of these genes has a different location on a chromosome. In fact, several genes determining a trait do not have to be located on the same chromosome. Traits that are governed by more than one gene are said to have polygenic inheritance. Traits with polygenic inheritance tend to show a wide range of variation.

The term “polygenic inheritance” is used to refer to the inheritance of quantitative traits, traits which are influenced by multiple genes, not just one. In addition to involving multiple genes, polygenic inheritance also looks at the role of environment in someone’s development.

Because many traits are spread out across a continuum, rather than being divided into black and white differences, polygenic inheritance helps to explain the way in which these traits are inherited and focused. A related concept is pleiotropy, an instance where one gene influences multiple traits.

Early Mendelian genetics focused on very simple genetic traits which could be explained by a single gene. For example, a flower might appear in either orange or yellow form, with no gradation between the colors. By studying plants and the ways in which they mutated, early researchers were able to learn more about the gene which determined flower color. However, by the early twentieth century, people were well aware that most traits are far too complex to be determined by a single gene, and the idea of polygenic inheritance was born

One easily understood example of polygenic inheritance is height. People are not just short or tall; they have a variety of heights which run along a spectrum. Furthermore, height is also influenced by environment; someone born with tall genes could become short due to malnutrition or illness, for example, while someone born with short genes could become tall through genetic therapy. Basic genetics obviously wouldn’t be enough to explain the wide diversity of human heights, but polygenic inheritance shows how multiple genes in combination with a person’s environment can influence someone’s phenotype, or physical appearance.

Skin color is another example of polygenic inheritance, as are many congenital diseases. Because polygenic inheritance is so complex, it can be a very absorbing and frustrating field of study. Researchers may struggle to identify all of the genes which play a role in a particular phenotype, and to identify places where such genes can go wrong. However, once researchers do learn more about the circumstances which lead to the expression of particular traits, it can be a very rewarding experience.

In pleiotropy, on the other hand, one gene is responsible for multiple things. Several congenital syndromes are examples of pleiotropy, in which a flaw in one gene causes widespread problems for a person. For example, sickle cell anemia is a form of pleiotropy, caused by a distinctive mutation in one gene which leads to a host of symptoms. In addition to causing mutations, pleiotropy also occurs in perfectly normal genes, although researchers tend to use it to track and understand mutations in particular.

 

Human eye color is a good example of polygenic inheritance. Human eyes may range in color from light blue to dark brown. Eye color is determined by the amount of the pigment melanin present in the eye. A small amount of melanin makes the eye color blue. More melanin makes the eyes look green, and still more makes them appear brown.

Several different genes control the production of melanin. Some alleles of the genes produce large amounts of melanin, and some produce less. The more alleles for heavy melanin production a person has, the darker the eyes will be.

As in eye color, the effects of different skin color genes work together to produce the phenotype. Each gene directs the heavy or light production of melanin. If most of the alleles are for heavy melanin production, their effects will combine to produce dark skin. If most of the alleles are for light production of mel­anin, their effects will combine to produce light skin.

Many human characteristics, such as height and facial fea­tures, are the result of polygenic inheritance. Many of the genes involved in such traits also have multiple alleles. This helps to explain the enormous variety in human appearance.

         Genetics is the science that learns the peculiarities of the hereditary and variability, which are the main characteristics of living things.

 

Human genetics is the science that learns the peculiarities of the hereditary and variability in human organism.

 Heredity is the transmission of characteristics from parent to offspring through the gametes.

Inheritance is the way of passing of hereditary information  which depends on the forms of reproduction. During asexual reproduction the main traits are inherited through spores or vegetative cells, that’s why the maternal and daughter cells are very similar. During sexual  reproduction the main traits are inherited through gametes.

 Gene is a unit of heredity, a segment of a  DNA that contains all the information required for synthesis of polypeptide chain. Each gene has a specific position (locus) on a chromosome.

 Genotype is the genetic constitution of an organism (a diploid set of genes).

 Genome  is a collection of  genes of an organism in sex cells (a haploid set of genes).

 Allele is an alternate form of a gene that can occupy a particular chromosomal locus. In humans and other diploid organism there are two alleles, one on each chromosome of a homologous pair. An individual who has two identical alleles for a gene at a particular locus on homologous chromosomes is homozygous for that gene. An individual with two different alleles at a particular locus on homologous chromosomes is heterozygous.

 The allele that masks the other in heterozygous is completely dominant, and the masked allele is recessive.

 When a gene has two alleles, it is common to symbolize the dominant allele with a capital letter, and the recessive with the corresponding small letter. If both alleles are recessive, the individual is homozygous recessive (aa). An individual with two dominant alleles is homozygous dominant (AA). An individual with Aa  alleles is a heterozygote.

The genotype describes the organism’s alleles, whole the phenotype describes the outward expression (physical appearance of an individual) of an allele combination. The phenotype of an individual is the observable outward manifestation of the genes that it carries.

Gregor Mendel laid the groundwork for understanding patterns of inheritance

 

Mendel’s Laws of inheritance.

 1.  The law of segregation.

Mendel crossed yellow seeds of pea Pisum sativum (AA) with green seeds plants (aa). The resulting seeds grew into F₁ plants of the same phenotype (yellow) and genotype (Aa).

P (Parental Generation):               ♀  AA               x                       ♂  aa

G (Gametes):                                   A                                            a

F₁ (First Filial Generation):                                       Aa    

A cross between plants obtained from F₁ plants.

 P:       ♀ Aa            x            ♂ Aa

G:        A, a                         A, a      

         F₂ (Second Filial Generation):  AA; Aa; Aa; aa

During this crossing the genotypic ratio expected of this monohybrid cross is 1:2:1.     The corresponding phenotypic ratio is three yellow  plants to one green plant, a 3:1 ratio.

The law of segregation states that from a pair of contrasting characters (alleles) only one is present in a single gamete and in F₂ these characters are segregated in the ratio of three to one (3:1) by phenotype and 1:2:1 by genotype.

When gametes are formed in heterozygous diploid individuals, the two alternative alleles segregate from one another.

The crosses that involve only one trait are called monohybrid crosses.

 

2.  The law of independent assortment.

 The cross between individuals, which differ in two traits are called  dyhybrid crosses.

   Mendel examined the inheritance of two different traits, each of which has two different alleles: he looked at seed shape, which may be either round (B) or wrinkled (b), and second color, which may be either yellow (A) or green (a).

P :               ♀  AABB               x                   ♂ aabb

G :                  AB                                          ab

F₁:                  AaBb

                      round yellow seeds   

Next, Mendel took F₁ plants (genotype AaBb) and crossed them to each other.

P :                 ♀  AaBb                          x                   ♂ AaBb

G :                 AB, Ab, aB, ab                                 AB, Ab, aB, ab

 F₂:

	AB	Ab	aB	ab
AB	AABB	AABb	AaBB	AaBb
Ab	AABb	Aabb	AaBb	Aabb
aB	AaBB	AaBb	aaBB	aaBb
ab	AaBb	Aabb	aaBb	aabb

   

 Punnet square for this cross predicts that the four types of seeds – round yellow (AABB, AaBB, AABb and AaBb); round green (aaBB, aaBb); wrinkled yellow (AAbb, Aabb); and wrinkled green (aabb) – will occur in the ratio 9:3:3:1, just as Mendel found.

Based upon the results of the dihybrid cross, Mendel proposed what is now know as the law of independent assortment, which states that a gene for one trait does not influence the transmission of a gene for another trait. This law is true only for genes on different chromosomes.  The seed shape and seed color genes that Mendel worked with meet this criterion.

Mendel’s laws apply to all diploid species. The nature of the phenotype is important when evaluating transmission of Mendelian traits. In humans, disorders or traits caused by a single gene are called Mendelian traits. For example, uncombable hair, misshapen toes or teeth, pigmented tongue tip, lack of teeth or eyebrows, duckbill-shaped lips and others.

         Many traits in humans also exhibit dominant or recessive inheritance, in a manner similar to the traits Mendel studied in peas.

 

Some dominant and recessive traits in humans

        

1. Multiple alleles condition.

2. Inheritance of human ABO-blood groups.

3. Rhesus blood types or Rh factor in man. Significance inheritance of ABO blood types and the Rh blood factor for medicine.

4. Rh incompatibility as the cause of erythroblastosis fetalis.

 

The I^A and I^B alleles are codominant, they segregate between generations, these both alleles are expressed simultaneously in heterozygous. There are several conditions where a single characteristic may appear in several different forms controlled by three or more alleles, of which any two may occupy the same gene loci on homologous chromosomes. This is known as the multiple alleles condition and it controls such traits as coat colour in mice, eye colour in mice and blood group in humans.

Three common alleles (multiple alleles) for the same gene of 9 chromosome control the inheritance of ABO blood type. These alleles determine the presence or absence of antigens on surface on the red blood cells (RBC). Using the symbol I to designated the ABO locus. They are I^A, I^B and  i. I^A and I^B are dominant to i. People with type A blood may be either genotype  I^A I^A or I^A i , type B corresponds to I^B I^B or I^B i, type AB to I^A I^B. Blood types are inherited according to simple Mendelian principles. The production of cell antigens is coded by a particular gene. Allele I^A  provides the code for the synthesis of a specific glycoprotein, antigen A which is expressed on the red blood cells. Allele I^B leads to the production of a different (but related) glycoprotein, antigen B. The allele i does not code for an antigen.

Antibodies anti-A and anti-B are proteins that appear in the plasma (fluid component of blood) of person lacking the corresponding antigens on their red blood cells. Antibodies are proteins produced by the immune system that combine with specific antigens; hence, anti-A combines with antigen A. Because of their specificity for the corresponding antigens, these antibodies are used in standard tests to determine blood type.

 The blood of a person in group A contains b antibodies in the plasma and A antigens on the red blood cells, whereas that of a person in group B contains a antibodies and B antigens. A mixture of these two blood types will always produce agglutination. The blood of a person in group AB contains both A and B antigens but no antibodies. The blood of person in the group (O) contains both kinds of antibodies, but there are no antigens on the cells.

 So, you must know about ABO blood type for 1) determining of the blood group; 2) blood transfusion; 3) in paternity suits. Blood type tests caever prove that a certain person is the parent of a particular child; thay can determineonly whether he or she could be. For example, it is possible, but not definite, that a man with type A blood (having genotype I^A i ) is the father of a child with type O blood. Sometime a blood test can prove that a man is not the father. For example, a man with type AB blood cannot possibly be the father of a child will type O blood. 

Another sets of cell surface markers on human red cells are the RH blood group antigens, named for the rhesus monkey in which they first described. This trait (antigen) is controlled by a single allele pair in 1 chromosome. The rhesus-positive allele Rh is dominant over the rhesus-negative allele rh. About 85 % of adult humans have the Rh cell surface marker on their red blood cells, and are called Rh-positive (RhRh, Rhrh). Rh-negative persons lack this cell surface marker because they are homozygous recessive for the gene encoding it (rhrh).

If an Rh-negative person is exposed to Rh-positive blood, the Rh surface antigens of that blood are treated like foreign invaders by the Rh-negative person’s immune system, which proceeds to make antibodies directed against the Rh antigens. This most commonly happens when an Rh-negative woman may have children who are Rh positive if the father is Rh positive. In the first pregnancy, this factor causes no complication, but during birth, blood cells of the child enter the mother’s bloodstream, where they induce the production of “anti-Rh” antibodies. Then, in subsequent pregnancies, antibodies from the mother pass to the fetus and cause its red blood cells to clump, leading to condition called erythroblastosis fetalis. So many fetal red blood cells are destroyed that the fetus dies before birth.

Red blood cell compatibility

 

Blood group AB individuals have both A and B antigens on the surface of their RBCs, and their blood serum does not contain any antibodies against either A or B antigen. Therefore, an individual with type AB blood can receive blood from any group (with AB being preferable), but can donate blood only to another type AB individual.

 

·Blood group A individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen. Therefore, a group A individual can receive blood only from individuals of groups A or O (with A being preferable), and can donate blood to individuals with type A or AB.

Blood group B individuals have the B antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the A antigen. Therefore, a group B individual can receive blood only from individuals of groups B or O (with B being preferable), and can donate blood to individuals with type B or AB.

 

Blood group O (or blood group zero in some countries) individuals do not have either A or B antigens on the surface of their RBCs, but their blood serum contains IgM anti-A antibodies and anti-B antibodies against the A and B blood group antigens. Therefore, a group O individual can receive blood only from a group O individual, but can donate blood to individuals of any ABO blood group (ie A, B, O or AB). If anyone needs a blood transfusion in a dire emergency, and if the time taken to process the recipient’s blood would cause a detrimental delay, O Negative blood can be issued. In addition to donating to the same blood group; type O blood donors can give to A, B and AB; blood donors of types A and B can give to AB.

 

Assumes absence of atypical antibodies that would cause an incompatibility between donor and recipient blood, as is usual for blood selected by cross matching.

 

 

 

RBC Compatibility chart

 

1.   Forms of interaction between allelic genes: complete dominance, incomplete dominance, superdominance, codominance.

2.   Forms of interaction between non-allelic genes: epistasis, complementarity, continuous variation (polimery).

3.   Qualitative and quantitative traits.

4.   Multifactorial traits

5. Pleiotropy – the multiple effect of a gene.

Allelic genes  control the two alternative expressions of the same character and have the same loci (sites) in the homologous chromosomes.     

Non-allelic genes  have  the different loci (sites) in the homologous chromosomes or are situated in the different (non-homologous) chromosomes.

Forms of interaction between allelic genes.

1.  Complete dominance – one allele in heterozygous completely masks the other allele. Example: complete dominance in pea seed.  A cross between homozygous dominant  plants with yellow seed (AA)  and homozygous recessive plant with green seed  (aa) produces a heterozygous plant with yellow seed  (Aa).

 

2.     Incomplete dominance – heterozygous phenotype intermediate between the two homozygous. Example: incomplete dominance in snapdragon flowers. A cross between a homozygous dominant plant with red flowers (RR) and homozygous recessive plant with white flowers (rr) produces a heterozygous plant with pink plowers (Rr). When Rr pollen fertilizes Rr egg cells, one-quarter of the progeny are red-flowered (RR), one-half are pink flowered (Rr) and one-quarter are white-flowered (rr). The phenotypic ratio of this monohybrid cross is 1:2:1 (instead of 3:1 in cases of complete dominance) because the heterozygouse class has a phenotype different from that of the homozygous dominant class.

3.  Superdominance – one dominant allele in heterozygous has more expressive manifestation than in homozygous state. Example. Dominant gene B determines brachydactyly (short fingers). Homozygous dominant persons with genotype BB don’t survive, they die in the embryonic stage.

 

 4.  Codominance – is the manifestation in heterozygous state traits, which are defined by two genes. Example. Codominance in Human ABO Blood Types.

 

Forms of interaction betweeon-allelic genes:

 

 1.  Epistasis occurs when one gene masks the phenotypic effect of another entirely different gene. A pair of genes at one locus may prevent the expression of a pair of genes at another locus. Such genes are called epistatic genes. Example. The color of some fowls is result of interaction between two non-allelic genes: C – gene of colored fowls, c – gene of white fowls, I – gene, that masks the phenotypic effect of gene C (epistatic gene), i – gene, that does not masks the phenotypic effect of gene C.  A cross between a homozygous dominant white fowl CCII and homozygous recessive white fowl ccii produces dihybrid white fowls in F_1. When the CcIi fowls are inbred, F₂ includes white and coloured fowls in the ratio of 13:3.

 

2 Epistasis is when the effect of one gene depends on the presence of one or more ‘modifier genes’ (genetic background). Similarly, epistatic mutations have different effects in combination than individually. It was originally a concept from genetics but is now used in biochemistry, population genetics, computational biology and evolutionary biology. It arises due to interactions, either between genes, or within them leading to non-additive effects. Epistasis has a large influence on the shape of evolutionary landscapes which leads to profound consequences for evolution and evolvability of traits.

Sign epistasis occurs when one mutation has the opposite effect when in the presence of another mutation. This occurs when a mutations that is deleterious on its own can enhance the effect of a particular beneficial mutation. For example, a large and complex brain is a waste of energy without a range of sense organs, however sense organs can be more useful if the organisms brain is better able to process the information.

At its most extreme, reciprocal sign epistasis occurs when two deleterious genes are beneficial when together. For example, producing a toxinalone can kill a bacterium, producing a toxin exporter alone can waste energy, but producing both can improve fitness by killing competing organisms.

Reciprocal sign epistasis also leads to genetic supression whereby two deleterious mutations are less harmful together than either one on its own, i.e. one compensates for the other. This term can also apply sign epistasis where the double mutant has a phenotype intermediate between those of the single mutants, in which case the more severe single mutant phenotype is suppressed by the other mutation or genetic condition. For example, in a diploid organism, a hypomorphic (or partial loss-of-function) mutant phenotype can be suppressed by knocking out one copy of a gene that acts oppositely in the same pathway. In this case, the second gene is described as a “dominant suppressor” of the hypomorphic mutant; “dominant” because the effect is seen when one wild-type copy of the suppressor gene is present (i.e. even in a heterozigote). For most genes, the phenotype of the heterozygous suppressor mutation by itself would be wild type (because most genes are not haplo-insufficient), so that the double mutant (suppressed) phenotype is intermediate between those of the single mutants.

When two mutations are viable alone but lethal in combination, it is called Synthetic lethality or unlinked non-complementation.

 

4.  Continuous variation (polimery). Different dominant non-allele’s genes affect on one trait, making it more expressive. Traits determined by more than one gene are polygenic – meaning “many genes” – or quantitative traits. Usually, several genes each contribute to the overall phenotype in equal, small degrees. The combined actions of many genes produce a continuum, or continuously varying expression, of the trait. Example. Height and skin color are familiar examples of polygenic traits in humans.

 

Qualitative traits are the classical Mendelian traits which have two contrasting conditions controlled by a single pair of genes. These traits may pertain to form (smooth and wrinkled pea seed), size (tall and dwarf pea plant), and so on. 

 

 5. Complementarity is an interaction between the products of two genes in which each of them gives characteristic phenotype in the end. Example. The colour of some flowers is the  result of interaction between two dominant genes (A and B), that’s why when one of them is absent, all flowers has white colour. During crossing plants with genotypes AAbb and aaBB, which have white colour, in the first filial generation all flowers have red color, but in the second filial generation the phenotypic ratio is 9 red colored to 7 non-colored flowers.

 

Pleiotropy. Often an individual allele will have more than one effect on the phenotype. Such allele is said to be pleiotropic. Pleiotropic relationships occur because in examine the characteristics of organisms, we are studying the consequences of the action of products made by genes. These products often also perform other functions about which we are ignorant. Pleiotropy occurs in genetic diseases that affect a single protein found in different parts of the body. This is the case for Marfan syndrome, an autosomal dominant defect in elastic connective tissue protein called fibrillian. Fibrillian is abundant in the lens of the eye, in the aorta, and in the bones of the limbs, fingers, and ribs. Marfan syndrome symptoms include lens dislocation, long limbs, spindly fingers, and a caved in chest.

 

Pleiotropy occurs when one gene influences multiple, seemingly unrelated phenotypic traits, an example being Phenylketonuria, which is a human disease that affects multiple systems but is caused by one gene defect. Consequently, a mutation in a pleiotropic gene may have an effect on some or all traits simultaneously. Pleiotropic gene action can limit the rate of multivariate evolution when natural selection, sexual selection or artificial selection on one trait favours one specific version of the gene (allele), while selection on other traits favors a different allele. The underlying mechanism of pleiotropy in most cases is the effect of a gene on metabolic pathways that contribute to different phenotypes. Genetic correlations and hence correlated responses to selection are most often caused by pleiotropy.

Рleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets.

A classic example of pleiotropy is the human disease PKU (phenylketonuria). This disease can cause mental retardation and reduced hair and skin pigmentation, and can be caused by any of a large number of mutations in a single gene that codes for the enzyme (phenylalanine hydroxylase), which converts the amino acid phenylalanine to tyrosine, another amino acid. Depending on the mutation involved, conversion of phenylalanine to tyrosine is reduced or ceases entirely. Unconverted phenylalanine concentrates in the bloodstream and can rise to levels that are toxic to the developing nervous system of newborn and infant children and which can cause effects such as mental retardation and abnormal gait and posture.

Because tyrosine is used by the body to make melanin (an important component of the pigment found in hair and skin) the failure to convert normal levels of phenylalanine to tyrosine results in less pigmentation being produced causing the fair hair and skin typically associated with phenylketonuria.

By excluding phenylalanine from the diet until adulthood, it is possible to avoid injury to the developing nervous system, neutralizing the particular effects that can result from toxic levels of phenylalanine, without having any effect on the low pigmentation production caused by the reduced levels of tyrosine.

Other well-known examples of pleiotropy include albinism and sickle-cell anemia.

A gene recently discovered in laboratory house mice, termed “mini-muscle,” causes a 50% reduction in hindlimb muscle mass as its primary effect (the phenotypic effect by which it was originally identified: in addition to various effects on behavior, skeletal morphology, relative size of internal organs, and metabolism. The mini-muscle allele behaves as a Mendelian recessive.

 

Clinical considerations. Marfan syndrome an autosomal dominant defect in elastic connective tissue protein called fibrillian. Fibrillian is abundant in the lens of the eye, in the aorta, and in the bones of the limbs, fingers, and ribs. Marfan syndrome symptoms include lens dislocation, long limbs, spindly fingers, and a caved in chest.

 

 

 

Multifactorial traits are the traits molded by one or more genes plus the environment. Example.  Multifactorial traits in humans include shizophrenia, homosexuality, and intelligence.

 

Мultifactorial inheritance is responsible for the greatest number of individuals that will need special care or hospitalization because of genetic diseases. Up to 10% of newborn children will express a multifactorial disease at some time in their life. Atopic reactions, diabetes, cancer, spina bifida/anencephaly, pyloric stenosis, cleft lip, cleft palate, congenital hip dysplasia, club foot, and a host of other diseases all result from multifactorial inheritance. Some of these diseases occur more frequently in males. Others occur more frequently in females. Environmental factors as well as genetic factors are involved.

Multifactorial inheritance was first studied by Galton, a close relative of Darwin and a contemporary of Mendel. Galton established the principle of what he termed “regression to mediocrity.” Mendel studied discontinuous characters, green peas vs. yellow peas, tall vs. dwarf, etc. There was no overlap of phenotype in Mendel’s studies. Characters fit into one of two classes. There was no blending in the heterozygote. On the other hand, Galton studied the inheritance of continuous characters, height in humans, intelligence in humans, etc. Galtooticed that extremely tall fathers tended to have sons shorter than themselves, and extremely short fathers tended to have sons taller than themselves. “Tallness” or “shortness” didn’t breed true like they did in Mendel’s pea experiments. The offspring seemed to regress to the median, or “mediocrity.” Figure 12 shows the correlation between the father’s height and the height of the son.

 

Multifactorial inheritance means that many factors are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition. Often one gender (either males or females) is affected more frequently than the other in multifactorial traits.

Multifactorial traits do recur in families, because they are partly caused by genes. The chance for a multifactorial trait or condition to happen again depends upon how closely the family member with the trait is related to you. For example, the risk is higher if your brother or sister has the trait or disease, than if your first cousin has the trait or disease. Family members share a certain percentage of genes in common, depending upon their relationship. For example:

 

 

 

 

Examples of multifactorial traits and diseases include: height, neural tube defects, and hip dysplasia.

Height

Height is determined by both genetic and environmental factors. Some people may be exceptionally short or exceptionally tall, often due to some gene with a major effect on height. Otherwise, children are often a height similar to, or “in-between” their parents, or simply closer to the population average.

 

Neural tube defects

Neural tube defects, spina bifida (open spine), and anencephaly (open skull), are seen in one in every 1,500 live births per year. During pregnancy, the human brain and spine begin as a flat plate of cells, which rolls into a tube, called the neural tube. If all or part of the neural tube fails to close, leaving an opening, this is known as an opeeural tube defect, or ONTD. This opening may be left exposed, or covered with bone or skin.

Anencephaly and spina bifida are the most common ONTDs, while encephaloceles (where the brain or its coverings protrude through the skull) are much rarer. Anencephaly occurs when the neural tube fails to close at the base of the skull, whereas spina bifida occurs when the neural tube fails to close somewhere along the spine. Babies with anencephaly are stillborn or usually live for a very short time after delivery. Babies born with spina bifida may have minor or temporary problems, or may have permanent, often serious, physical problems. These may include paralysis, lack of bowel and bladder control, club feet, hydrocephaly (a buildup of spinal fluid in the head), and intellectual disability. In most cases, one or more surgeries after birth may be needed.

 

ONTDs occur in children without a prior family history of these defects in most cases. ONTDs result from a combination of genes inherited from both parents, coupled with environmental factors. Some of the environmental factors include uncontrolled diabetes in the mother, and use of certain prescriptions medications. ONTDs are seen five times more often in females than males. Once a child has been born with an ONTD in the family, the chance for an ONTD to happen again in a future pregnancy is increased. It is important to understand that the type of neural tube defect can differ the second time. For example, one child could be born with anencephaly, while the second child could have spina bifida.

The neural tube closes 28 to 32 days after conception, before many women are aware they are pregnant. Folic acid is a B vitamin reduce the chance for neural tube defects. For this reason, experts recommend all women in their reproductive years take a multivitamin containing folic acid. However, do not take more than one multivitamin per day.

If a couple has had a previous child with an ONTD, a larger amount of folic acid is recommended. The CDC recommends that a woman take 4.0 mg (4,000 mcg) of folic acid one month before becoming pregnant (before conception). To obtain this amount of folic acid, you must get a prescription from your health care provider.

ONTDs can be diagnosed before birth by measuring a protein called AFP (alpha-fetoprotein) present in the amniotic fluid around the baby. Fetal ultrasound during pregnancy can also give information about the possibility of an ONTD, but is not always accurate, since some babies with an ONTD may look the same on ultrasound as those without these defects. Measurement of the AFP, and other biochemical markers from amniotic fluid, is over very accurate for detecting ONTDs. Small or closed defects (which do not leak spinal fluid) may not be picked up by this test.

 

For all women who are pregnant who have not previously had a child with an ONTD and do not have a family history of ONTDs, the American College of Obstetrics and Gynecology (ACOG) recommends that a blood test be offered between 15 to 20 weeks, to measure AFP (and other biochemical markers) to determine whether a pregnancy is at increased risk for an ONTD. Although this test (sometimes called maternal serum screening, the double screen, triple, or quadruple screen) does not tell a couple for certain whether their baby has an ONTD, it will determine which pregnancies are at greater risk, so that additional testing will be offered.

This tutorial explored the more complex expression patterns of alleles. These patterns of expression do not contradict the ideas and conclusions of Mendel,  but show that genes and their products can interact and/or be expressed in more complex ways. In all cases, these genes are still transmitted from generation to generation as distinct alleles on chromosomes that segregate independently during meiosis. The differences lie in how the gene product behaves within the cell, and the number of such products that contribute to a given character trait.

Some alleles can show incomplete dominance. In the snapdragon flower color we saw that three phenotypes could be traced to two alleles. In other words, two separate homozygous phenotypes resulted (as is usually seen with characters transmitted in a Mendelian manner) and a third phenotype associated with a heterozygous genotype (clearly different than the case observed with Mendelian traits, where the heterozygous phenotype is the same as the homozygous dominant genotype). How can two alleles yield three phenotypes? Consider the snapdragon. When a plant receives two alleles (a double dose) of the red allele, the flower is very red. These alleles encode for enzymes involved in the production of red pigment. The alternative alleles produce an enzyme that is nonfunctional and cannot participate in pigment synthesis. When a plant receives two copies of this nonfunctional alternative allele, pigment is not produced and the flower is white. When the plant receives one copy (a single dose) of the functional red allele, it can produce some pigment, but not as much as with two fully functional alleles, and so, the color is less red (pink).

In the example above, note that the reason for the phenotypic pattern was that one allele was nonfunctional and the other functional allele resulted in a phenotype that was dependent on there being one or two copies of the functional alleles. There is another situation, however, termed codominance, in which both alleles are functional and expressed. The M and N blood groups are examples of codominance. These alleles encode for proteins that are located on the surface of red blood cells. They are similar but not identical; they differ in four amino acids. If the individual is homozygous, then the phenotype is either M or N. If heterozygous, however, then both proteins are expressed on the surface of red blood cells.

So far we have considered fairly simple cases, where the number of alleles is limited to two. In fact, many genes have multiple alleles. This may seem impossible because in the diploid state there is only room for two alleles (one on the maternal chromosome and one on the paternal chromosome) of a gene. At the population level, however, many more allele forms are possible (although in any given diploid individual, only two occur at any given time). The ABO blood type is one example.

In some cases, genes and their alleles may be expressed in complex ways. That is, no single trait can be attributed to a given allele. Pleiotropy describes this situation, and includes the examples of pigmentation and crossed eyes in the case of albinism.

In the case where one gene product is used by (or dependent on) another product, epistasis can occur. This is fairly common because gene products do not function in isolation. In the example of fur color in mice, one can see that pigment synthesis and pigment deposition are two processes that must occur in order for a specific phenotype (i.e., color) to be observed.

Lastly, we considered the case of polygenic inheritance, whereby many genes and their alleles are involved in the expression of a given phenotype. If you think about it, you will likely recognize that polygenic inheritance and epistasis are related. In fact, many traits are determined by multiple genes, which makes the analysis of expression patterns complex.