Is existence of different alleles for a gene a result of mutation?

Is existence of different alleles for a gene a result of mutation?

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I would like to understand evolution. Here are a few questions

  1. Why are there different alleles for a gene?
  2. Is the different alleles of a gene are mutated versions of a gene?
  3. Why selection pressure favoured the existence of more than one alleles?

I would like to understand evolution

The best way to do so is to start an introductory course on evolutionary biology. Consider having a look at evo101 for example.

Why are there different alleles for a gene?

Because mutations bring variation. Note that not all genes are polymorphic. In other words, there might be genes for which, all individuals in the population share the same allele.

The existence of this genetic variance is absolutely central to the whole concept of evolution. In short, mutations increase genetic variance while natural selection and genetic drift reduce it.

Is the different alleles of a gene are mutated versions of a gene?


Why selection pressure favoured the existence of more than one alleles?

In the exception of cases of balancing selection (e.g. heterozygote advantage, negative frequency-dependent selection), selection does not yield to the existence of genetic variance, rather the opposite in fact. Selection "selects" for a given allele, which in turn reduces the genetic variance. Mutations bring new genetic variance in populations and selection reduces it. Genetic drift (another "driver of evolution") also reduces genetic variance.

1. Why are there different alleles for a gene?

Variants of a gene are called alleles. In other words, an allele is one of the possible forms of a gene. If there is genetic variation in a population (and in all species, there is variation), then there are multiple alleles.

Evolution reflects changes in DNA sequences and allele frequencies within a species over time. These changes may be due to mutations, which introduce new alleles into a population. New alleles can also, for instance, be introduced in a population by gene flow, when two populations that carry unique alleles breed together.

2. Are different alleles of a gene mutated versions of that gene?


3. Why does selection pressure favored the existence of more than one allele?

This question is unclear and/or poorly-stated. Are you asking why there is variation in a population? The answer is that, in spite of the fact that DNA replication (copying) is high-fidelity and quite accurate, it is imperfect. This means that over a long lineage of inheritance, new alleles will emerge, and their frequency in the population will change. Also, DNA accumulates damage and mutations occur due to chemical factors. DNA is not a perfectly stable molecule. Mechanisms of repair of DNA exist but are imperfect. It is impossible for a species to maintain perfect genetic identity, especially over prolonged periods of time, when mutations accumulate.

If you are asking why variation (or more strictly, diversity) is favorable for a species, here is an excerpt from the Wikipedia entry on genetic diversity, which explains it concisely:

Genetic diversity serves as a way for populations to adapt to changing environments. With more variation, it is more likely that some individuals in a population will possess variations of alleles that are suited for the environment. Those individuals are more likely to survive to produce offspring bearing that allele.

There is also an important difference between diversity and variability to consider. Diversity is the total number of genetic characteristics in a population. Genetic variability is the generation or presence of genetic differences between individuals of a population. Variability is introduced through migration events, homologous recombination during meiosis, and other things.

Addendum/protip: asking why is often less fruitful than asking how. The how is mutation. The why makes me want to include thermodynamics and statistical mechanics as an explanation, which is definitely an unnecessarily complicated explanation.

1.why there are different alleles for a gene?

alleles of a gene are mutated versions of a gene

why selection pressure favoured the existence of more than one alleles?


1) No reason. Allele is both not 'selected for' nor 'selected against'. The allele do not cause detriment or advantage. It is a neutral mutation. An example is ear lob, connected or not connected. It does not affect hearing. It builds up in a population by chance due to the founder effect.

2) It has an advantage but only in heterozygous form. Example Sickle cell anemia. In homozygous form this allele is quite lethal. However in heterozygous form (ie pair with the normal allele), it confers resistance to the malaria parasite. So selection does favour the sickle cell anemia allele but only to a point. Once the allele becomes too common in the population it is selected against, as the probability of homozygous individuals of sickle cell allele occurring becomes more common.

3) Because allele is selected for in some parts of organism's ecological range. Example human skin colour. Human range from poles of the earth to the equator. And thus are exposed to varying light intensity. At the equator, dark, almost black pigmentation is favoured as it protects against sun damage (ie sun burn) and skin cancer. Up in the temperate region, fair almost white skin is an advantage as it allows better absorption of the limited UV light for vitamin D and folic acid production, which is required for bone and limb development. Different light intensity selects for different levels of skin pigmentation. So we have several skin alleles.

4.4: Types of Mutations

  • Contributed by Todd Nickle and Isabelle Barrette-Ng
  • Professors (Biology) at Mount Royal University & University of Calgary

Mutations (changes in a gene sequence) can result in mutant alleles that no longer produce the same level or type of active product as the wild-type allele. Any mutant allele can be classified into one of five types: (1) amorph, (2) hypomorph, (3) hypermorph, (4) neomorph, and (5) antimorph.

  • Amorph alleles are complete loss-of-function. They make no active product &ndash zero function. The absence of function can be due to a lack of transcription (gene regulation mutation) or due to the production of a malfunctioning (protein coding mutation) product. These are also sometimes referred to as a Null allele.
  • Hypomorph alleles are only a partial loss-of-function. They make an incompletely functioning product. This could occur via reduced transcription or via the production of a product that lacks complete activity. These alleles are sometimes referred to as Leaky mutations, because they provide some function, but not complete function.

Both amorphs and hypomorphs tend to be recessive to wild type because the wild type allele is usually able to supply sufficient product to produce a wild type phenotype (called haplo-sufficient - see Chapter 6). If the mutant allele is not haplo-sufficient, then it will be dominant to the wild type.

While the first two classes involve a loss-of-function, the next two involve a gain-of-function &ndash quantity or quality. Gain-of-function alleles are almost always dominant to the wild type allele.

  • Hypermorph alleles produce more of the same, active product. This can occur via increased transcription or by changing the product to make it more efficient/effective at its function.
  • Neomorph alleles produce an active product with a new, different function, something that the wild type allele doesn&rsquot do. It can be either new expression (new tissue or time) or a mutation in the product to create a new function (additional substrate or new binding site), not present in the wild type product.

Antimorph alleles are relatively rare, and have an activity that is dominant and opposite to the wild-type function. These alleles usually have no normal function of their own and they interfere with the function from the wild type allele. Thus, when an antimorph allele is heterozygous with wild type, the wild type allele function is reduced. While at the molecular level there are many ways this can happen, the simplest model to explain antimorph effect is that the product acts as a dimer (or any multimer) and one mutant subunit poisons the whole complex. Antimorphs are also known as dominant negative mutations.

Identifying Muller&rsquos Morphs - All mutations can be sorted into one of the five morphs base on how they behave when heterozygous with other alleles &ndash deletion alleles (zero function), wild type alleles (normal function), and duplication alleles (double normal function).

Is existence of different alleles for a gene a result of mutation? - Biology

Chapter 12: Gene Function, Gene Regulation, and Biotechnology

You have open access (no log-in or password needed) to instructional materials on the Text web site. Select "Resources" from the upper left of the page and select the text chapter you want.


You may also ask questions and see answers to your classmates' questions in Moodle in the "Talk to Ed" forum.


The content of this lecture will help you complete these assignments:

Second Moodle Assignment, due in your TA's Moodle Forum by 8 AM Tuesday March 30.

After studying this material you should be able to:

Draw a diagram, create a concept map, or write a paragraph that explains the relationships among these terms:

DNA nucleotide bases homologous chromosomes
genes gene loci alleles
gene expression proteins traits
sister chromatids

Use your chromosome models from discussion or lab to illustrate the location of a gene for the production of a particular protein. Illustrate the location of the gene on homologous chromosomes, as well as on sister chromatids.

Explain in general terms how the structure of the DNA molecule is related to the production of a specific protein.

Describe the connections among:

variations in the structure of the DNA molecule of a gene for a particular trait

the existence of different alleles for a gene

different proteins produced by different alleles for the same gene and

different expressions of the trait.

Explain in general terms how the order and kinds of amino acids that make up a protein determine its final conformation and, ultimately, its function.

Web Resources:

Glossary of Genetic Terms, from Lecture 11: Heredity and Meiosis

Genes and Disease (Selected genes and their functions and locations on the chromosomes) from the National Center for Biotechnology Information.

PREVIEW: Protein Synthesis for learning the details of protein synthesis (from Access Excellence). Print this out for next lecture.

REVIEW (DNA, Chromosomes, Genes)

What is DNA, Why do we need it, and Where does it come from?

One Nitrogenous Base (A, C, G, or T)

What are Chromosomes?

Human Chromosome. Electron micrograph of human chromosome. (Hoefnagels, Page 217, Fig. 11.3)

What are Genes?

What are Genes? from Access Excellence Resource Center. "Working Subunits of DNA." A sequence of DNA specifying the sequence of amino acids of a particular protein involved in the expression of a trait.

Different forms of the same gene are called alleles. Alleles are formed by mutations of pre-existing alleles. Different alleles produce variations in inherited characterisitics (traits).

Homologous Chromosomes Hoefnagels, pg. 182, fig. 9.7. Remember, you get one chromosome of each homologous pair from each parent (by way of their gametes). Homologous chromosomes have the same sequence of gene locations that control the same characteristics (traits). A gene locus (plural, loci) is the specific location of a gene on a particular chromosome. You have two copies of every gene, but the two members of any gene pair do not necessarily have identical DNA sequences. If you carry two different DNA sequences at a particular site on a chromosome (alleles), you are said to be heterozygous at that site. If you carry two identical alleles of a gene, you are homozygous.

Chromosomes 7. Zoom in and note cystic fibrosis (CFTR) locus listed on the right hand side about 1/5 the way up from the bottom of the illustration of Chromosome 7.

The Relationship Between Genes, Proteins, and Traits

A gene codes for a particular protein that is involved in the expression of a trait.

Characteristics determined by single genes are called Mendelian traits.

Cystic fibrosis is an example of a genetic disorder that follows Mendelian genetics (Hoefnagels, Figure 10.7, page 201). Over 5,000 human disorders are caused by mutations in single genes, such as sickle cell anemia and cystic fibrosis.

Genes and Disease (Selected genes and their functions and locations on the chromosomes) from the National Center for Biotechnology Information.

Gene Expression via Protein Synthesis, from Access Excellence. For a cell to make protein, DNA is used as a template to manufacture messenger RNA (transcription). mRNA moves to the ribosomes in the cytoplasm where it directs the assembly of amino acids that fold into completed proteins (translation).

How are genes linked to disease? Genetic diseases are the result of alterations in the normal sequence of nucleotides in a gene which results in an altered protein that has an altered function. Some protein changes are insignificant others are disabling. Also, see How does a faulty gene trigger disease?, from Access Excellence.

Cystic Fibrosis (An example of gene expression gone wrong)

Cystic Fibrosis from NCBI. CF is the most common fatal disease in the US today. It causes the body to produce a thick, sticky mucus that clogs the lungs, impairs breathing, and leads to infections. The pancreas also becomes clogged, stopping digestive enzymes from reaching the intestines where they are required to digest food. The pancreas form cysts and become fibrous.

CF is the most common inherited disease among Caucasians in US.

1 in 29 Caucasians (10 million) carries a defective allele for the CF gene.

30,000 children and young adults have CF.

Cystic fibrosis like sickle cell disease, is an autosomal recessive trait (See figure 10.7 in Hoefnagels, page 201) . See also Cystic Fibrosis, from Access Excellence, explaining the hereditary nature of the disease.

CF is caused by defective gene CFTR (Cystic Fibrosis Transmembrane Regulator Protein) on Chromosome 7. The normal gene produces an active transport protein that functions to pump salt (sodium and chloride) ions across membranes of epithelial cells that line the airways of the lungs and ducts of other organs. Mutations in the gene result in an alteration of the protein so that epithelial cells are defective in transporting these ions out of cells.

Because less salt is secreted from the cells lining these airways and ducts, there is less water "drawn out" of the cells. This causes the mucous that normally line these passageways to be unusually thick and sticky. The thick mucous clogs the passageways and harbors the growth of bacteria and fungi that cause further problems.

The role of the CTFR gene from the UK Cystic Fibrosis Gene Therapy Consortium. An excellent resource explaining how the chloride channel (CFTR protein) works.

CFTR genomic DNA sequence. Click here to see the DNA sequence of the CFTR gene. Click on the numbers along the line representing the gene to see the DNA sequence of different sections of the gene (its huge!).

Gene Mutations. There are over 1000 different mutated forms (alleles) of the CF gene. The severity of the disease is related to the particular mutation(s) that have been inherited.

Detailed data base of CFTR Mutations (Click on "Search" and then select a purple "exon" region on the gene diagram to see detailed info for mutations in each region.)

Summary: DNA to RNA to Protein to Trait. An excellent summary of the expression of the CFTR gene from Dr. Robert Huskey from the University of Virginia (Ret.).

Protein Structure

As a protein (polypeptide) is synthesized in a cell, it folds into a three-dimensional structure (conformation). The order and kinds of amino acids that compose a protein (polypeptide) determine its conformation. The final shape of a protein arises from its interactions with other proteins and other molecules, and determines its function. Errors in protein structure can cause diseases, such as sickle cell anemia or cystic fibrosis.

Hydrogen bonds between parts of the peptide backbone create the secondary structure. The polypeptide may be folded into several distinctive shapes, such as coils, sheets, loops, or combinations of these shapes.

Interactions among side chains (R groups) occur, folding the polypeptide into three dimensions and giving it a unique shape.

Insulin- 3D image of the insulin protein. from Endocrine System Hypertext - Colorado Sate University.

Cytochrome b one of the electron transport chain proteins in the mitochondria
Cytochrome b movie

RAS protein a protein involved in the control of cell division - mutant forms associated with cancer.
RAS protein movie

DNA Polymerase- 3D structure of the enzyme responsible for DNA replication.
DNA Polymerase movie

If you de-focus your eyes, such that your brain melds the two stereo images into a third image between the two on the screen, you can create a 3 dimensional image of the protein molecule in your brain.

The joining of different polypeptide units to form a larger, functional protein. The blood protein hemoglobin is composed of four polypeptide chains, encoded by two sets of genes.

Hemoglobin from The Worlds of David Darling Hemoglobin is made up of two alpha globin chains and two beta globin chains plus 4 heme groups that carry oxygen. In this illustration each of the 4 globin molecules is a different color. The 4 heme groups are blue in this illustration.

Sickle Cell Disease and natural Selection

This is an example of adaptation. Unique genetic information that determines the amino acid sequence in hemoglobin was acquired in regions where malaria was prevalent. Resistance to malaria resulted and survival improved. The consequence of this improvement is the possibility of Sickle Cell disease.

Biology Notes on Multiple Alleles | Genetics

The below mentioned article provides note on multiple alleles.

After Mendel first advocated the existence of two factors for each character, it was demonstrated in many organisms that a gene consists of a pair of alleles. Each member of the pair of alleles is said to occupy an identical position or locus on each of the two homologous chromosomes in diploid cells of an organism.

In Mendel’s experiment the gene controlling height of pea plants has both its alleles designated either as T and T or T and t, or t and t. Since there are always only two alleles they can also be denoted as T 1 and T 2 . Similarly the gene determining flower colour (R and r) can be denoted by alleles R 1 and R 2 .

Sometimes more than two alternative alleles or multiple alleles are present in different individuals of a population. When there are multiple alleles, a gene is denoted by more than two alleles such as T 1 , T 2 , T 3 , T 4 and R 1 , R 2 , R 3 , R 4 ,…… and so on.

Now there are only two homologous chromosomes in a diploid cell, and at one particular site of a gene or locus, only one allele can be present. Therefore, in one diploid cell only two alleles are present at a particular locus. In other members of the population, due to two or more mutations, the same locus on two homologous chromosomes could have two different alleles.

In this way it is possible to detect a number of alleles for one gene from their different expressions in different individuals. Such a system in which one gene has more than two allelic states at the same locus in different members of the population is known as a multiple allele system.

T.H. Morgan in 1910 described the first case of multiple alleles of a gene controlling eye colour in Drosophila during his studies on mutation. In a vial of flies with normal red eyes he found a fly with white eyes which had arisen due to a mutation in the gene which produces red colour in normal flies.

By performing genetic experiments, the position of this gene was determined to be on the X chromosome, the exact location being 1.5 units from the left end of this chromosome.

This location is identical to the position occupied by the gene which produces red colour in eyes. Later on some other flies were discovered with eye colour resembling the biological stain eosin. The gene for eosin colour was also found to be located at 1.5 units on the X chromosome.

When crosses were made between eosin flies and red, and between eosin and white it turned out that the gene for eosin was an allele to both red and white genes. This proves that genes producing red, white and eosin eyes in different flies are all alleles of each other. In other words the gene controlling eye colour in Drosophila has multiple alleles.

Later on a series of alleles producing eye pigments in different shades and intensities between red and white were found each shade has a different name such as wine, blood, coral, cherry, apricot, honey, pearl and ivory, and a few more. It also means that the different alleles become less and less efficient in producing the same kind of biochemical product.

Sometimes phenotypes produced by different alleles are not markedly different so that some of them appear close to the normal red. Such alleles with similar effects are referred to as isoalleles. There are wild- type isoalleles for genes expressing the wild phenotype. The mutant gene for white eye colour in Drosophila is composed of a series of multiple isoalleles W 1 , W 2 , W 3 etc. These are known as mutant isoalleles.

The Himalayan rabbit is a classic example for illustrating multiple alleles, first studied by Sturtevant in 1913. The wild type rabbit has grey fur and is called agouti rabbits with all white fur and pink eyes are albino the Himalayan has white fur on the body, but its feet, tail, ears and tip of nose are black (Fig. 5.1). When crosses were made between agouti and albino, and between agouti and Himalayan, both albino and Himalayan were found to behave as recessive to agouti.

When Himalayan and albino were crossed, F1 were all Himalayan, and in F2 3 Himalayan: 1 albino were produced. Clearly, Himalayan, agouti and albino all result from different alleles of the gene that controls fur or coat colour in rabbits. If C denotes the dominant allele that produces the wild agouti type of fur, then albino would have the genotype cc.

The cross of agouti (CC) and Himalayan (c h c h ) would give an F2 consisting of 3 agouti (CC, Cc h ) and one Himalayan (c h c h ). Similarly, the cross between Himalayan and albino (cc) would give an F2 of 3 Himalayan (c h c h , c h c) and one albino (cc). There is also a fourth allele for fur colour in rabbits called chinchilla (c ch ) which behaves like Himalayan.

Multiple Alleles and Complex Loci:

So far we have considered multiple alleles as a series of alternative forms of a gene present at the same locus. The earlier concept of genetic recombination implies crossing-over between genes, not within a gene. The idea was based on breakage and exchange of segments of paired homologous chromosomes, resulting in new linear arrangements of genes.

Genetically it could be observed in the test-cross progeny of a heterozygote and a homozygous recessive the frequency of recombinant phenotypes was used for gene mapping. The two genes involved in recombination must obviously occupy different loci.

In 1942, Oliver showed that in the case of lozenge eye alleles in Drosophila, crossing over could occur between alleles present in the same locus. But because at that time the gene was thought to be an indivisible unit, his view was not accepted.

Lewis found some other mutants in Drosophila which behaved in the same ways as the lozenge eye mutants. Since they could produce recombinant progeny in test crosses, due to crossing over between two mutant sites in a locus, it became doubtful that they were true alleles. The term pseudo-alleles was coined for such alleles.

The earlier concept of genes arranged like beads-on-a string had to be revised. A gene is a sequence of nucleotides in DNA that controls a specific gene product. The different mutations of the gene may be due to changes in single nucleotides at more than one locations in the gene. Crossing over could take place between the altered nucleotides within a gene.

Since the mutant nucleotides are placed so close together, crossing over is expected with a very low frequency. When several different genes which affect the same trait are present so close that crossing over is rare between them, the term complex locus is applied to them.

The term multiple alleles can also be redefined in the following way. Within the nucleotide sequence of DNA that represents a gene, multiple alleles are due to mutations at different points within the gene.

NCBI Gene & SNP Tutorial

The National Center for Biotechnology Information (NCBI) Gene database ( is an online resource to learn about gene sequences, gene alleles and mutations, genomes, and much more. It was created for the scientific community, but with a little effort and this guide, anyone with a basic understanding of genetics can learn to use it (see Table 3 for a list of resources to brush up on genetics). Following are instructions, tips, and advice on how to get started using this resource.

What can I use the NCBI Gene database for?

The NCBI Gene database has information on gene sequences, gene alleles and mutations, genomes, amino acid sequences for proteins, and much more genetic data on humans, as well as many other animal species. You can explore many resources on the NCBI Gene database. In this tutorial, you will use the database to look up a gene of interest and learn what specific mutations in that gene may cause certain genetic diseases. The end of this tutorial covers additional resources and the NCBI's own tutorials for learning more about other NCBI Gene functions and tools.

How can I look up a gene and find out more information about it?

Here we will show you how to look up a gene of interest to learn more about it. For the purpose of simplifying the directions, we will use cystic fibrosis as the example in this tutorial.

  1. Go to the NCBI Gene database website, shown in Figure 1: (Note: This link will open a new window so you can more easily follow the steps.)
  2. At the top, enter the name of your gene of interest and click "Search."
    1. For example, the gene that is mutated in cystic fibrosis is CFTR. (Note: If you were interested in a disease, but did not know the related gene(s), you could look that up using another Science Buddies resource, the Genetics Home Reference Tutorial.) To look up this gene, enter: CFTR

    Screenshot of the website homepage. A search bar appears at the top and quick links to resources and gene tools are located at the bottom of the page.

    Figure 1. The NCBI Gene database has information on gene sequences, gene alleles and mutations, genomes, and much more genetic data on humans and other animal species.

    1. The resulting page, shown in Figure 2, may have a long list of related results. The top results are usually the most relevant ones. You are looking for the first entry that both starts with your gene name and includes the species name for humans (Homo sapiens). In our CFTR example, this is the first result click on it to proceed to the gene page.

    Screenshot of search results on the website. Searching for the gene CFTR shows a list of results that provide a gene name, gene ID, description, location, aliases and a mendelian inheritance in man value (MIM). In this example the first result on the list is selected.

    Figure 2. When you enter a gene name, you will get many results on the NCBI Gene database. The gene name is given on the left, followed by its description (unabbreviated name) in the second column. The species name is given in brackets at the end of the description entry. Additional gene information, including the chromosome location, is given in the columns farther to the right. Pick the top gene result, (circled in red) for this tutorial.

    Screenshot of the website gene information page. The information page displays the specific gene at the top of the page with an abbreviation and full name written out. At the center of the page is a summary of information for the gene and a Genomic context section that provides additional information. To the right of the page two side bars display a table of contents for the gene information page and a related information page which links to additional resources.

    Figure 3. The NCBI gene database contains a large amount of information for any given gene. This tutorial explores the links in the sections titled "Table of contents" (circled in green), and "Related information" (circled in red), both on the right side of the page.

    Use the table of contents (circled in green in Figure 3) to navigate to different information on the gene page. Table 1 gives an overview of the different types of information provided.

    • Other animals this gene belongs to (under "Homology")
    • Pathways that this gene is involved in (under "Pathways from BioSystems")
    • The different functions the protein made from this gene has (under "Gene Ontology")

    Use the "Related information" section (circled in red in Figure 3) to navigate to additional NCBI pages with information on the gene and its role in human biology. Table 2 highlights some of the links that are particularly relevant to learning more about the gene's normal and disease functions.

    Link Name What Information It Provides
    BioProjects Chromosome and sequencing studies that have involved the gene.
    BioSystems Bodily functions the gene may be involved in.
    Conserved Domains Functional domains, which are DNA regions that form distinct protein structures that affect the overall function of the protein. Functional domains are shared, or "conserved," among different members of the same gene family.
    Full text in PMC Scientific articles, with free access to full text, published on the gene.
    GEO Profiles How much protein is made from this gene in different tissues and in scientific studies, referred to as the gene's expression profile.
    HomoloGene A list of potential homologs of the gene (evolutionarily related genes in different animals)
    Nucleotide Links to where you can find the DNA sequence of the gene.
    OMIM Information about the gene on the OMIM database. The links here discuss the history and discovery of the gene, its function, how the disease manifests, and more.
    Protein Links to where you can find the amino acid sequence of the protein the gene codes for.
    PubMed Scientific articles published on the gene. Note: Some articles cannot be freely accessed.
    RefSeq Proteins Amino acid sequence of the protein the gene codes for and additional gene information.
    RefSeq RNAs mRNA and amino acid sequences that the gene (DNA) codes for.
    RefSeqGene The genomic DNA sequence of the gene (includes introns and exons) and other information about the gene.
    SNP Links to where you can find short genetic variations of the gene.
    SNP: GeneView A list of short genetic variations of the gene and the functional amino acid changes they cause.
    Variation Viewer A list of the short genetic variations of the gene with a lot of information about the variations, including what the DNA mutations are and which variations are pathogenic.
    Table 2. On the right side of the NCBI Gene page for a given gene, there is a list of links in the "Related information" section (circled in red in Figure 3). This table shows what resources some of these links will provide.

    I want to look up a gene involved in a genetic disease and find out how it is mutated in that disease. How can I do this?

    Once you have completed the tutorial section "How can I look up a gene and find out more information on it?", here we will show how to find mutated versions of a gene that cause a genetic disease. For the purpose of simplifying the directions, we will use cystic fibrosis as the example in this tutorial.

    1. Once you have located the NCBI Gene page for your gene of interest (step 4), scroll down through the "Related information" section on the right (circled in red in Figure 3) until you see the "Variation Viewer" link (circled in red in Figure 4). Click on this link.

    Screenshot of the website gene information page. On the right side of the gene information page, under the sidebar titled related information, a link is labeled "Variation Viewer". This link is located at the end of the list of links for related information.

    Figure 4. Scroll down through the "Related information" section on the right side of your gene page until you see "Variation Viewer" (circled in red). Click on this link to learn about the different variations of this gene.

    1. A gene can have many different alleles, or alternative forms that occur through mutation of the DNA. Each row of data on this page, shown in Figure 5, lists a different allele for the gene you just searched for.
      1. On the left side of the page you can choose different options to filter the data. Click on "Pathogenic" and "Likely pathogenic" (circled in blue in Figure 5) to sort the alleles according to these criteria. Here are the different clinical interpretations for alleles:
        1. "Likely pathogenic:" Alleles that are thought to be likely to cause disease, but are not proven.
        2. "Pathogenic:" Alleles that have been proven to cause disease.
        3. Alleles for which the "Clinical interpretation" column is blank. There is "no data" for these alleles. These still could be pathogenic.

        Screenshot of an allele chart on the website. The variation viewer window displays an allele chart for a given gene at the top of the page. At the bottom-left of the page filters can be applied to the chart to find specific alleles, such as ones that could be potentially pathogenic. Directly underneath the chart is a list of variants of alleles that display the variation type and location.

        Figure 5. Clicking on "Variation Viewer" (circled in red in Figure 4), takes you to a table listing different alleles, or alternative forms that occur through mutation of the DNA, for your gene. Each row is a different allele of the gene. You can filter these alleles by their "Most severe clinical significance" (circled in blue), sort by "Variant type" (circled in green), or find more information about them by clicking on their "Variant ID" (circled in red).

        1. Once you have applied all your filter criteria (variant type, clinical significance, etcetera), click on the arrow to the left of the variant ID (circled in yellow in Figure 5 and Figure 6) to open a drop-down window that provides more information on this specific gene variant. Here you will find more allele information, such as the "Transcript change," which lists what the DNA mutation is (circled in green in Figure 6) or the "Protein change" that result from the mutation (circled in red in Figure 6).

        Screenshot of a list of variations in the variation viewer on the website. Variations in the variation viewer each have a small arrow to the left of each entry on the list. Clicking on the arrow of a specific allele variation shows additional information such as the transcript changes and protein changes in the variation.

        Figure 6. Clicking on the small arrow (circled in yellow) to the left of the variant ID (circled in blue), pulls up more allele information, such as the “Transcript change” (circled in green) or “Protein change” (circled in red).

        1. For each selected allele, click on its "Variant ID" link (circled in blue in Figure 6), to go to a new page with information on that specific allele. This information is part of the SNP Database (
          1. For each allele page, scroll down to the section titled "Gene View" shown in Figure 7.
          2. Look where "Residue change" is listed (circled in yellow in Figure 7), and there should be an amino acid mutation that matches the "Protein change" information that was listed with this allele on the previous page, which is circled in red in Figure 6.
            1. For example, the CFTR allele listed in Figure 6 had a protein mutation of "Met1Val" This means that the first amino acid in the protein has been changed from Methionine (abbreviated Met or M) to Valine (abbreviated Val or V). This matches the "Residue change," which is listed as "M [Met] ' V [Val]" at position "1".

            Screenshot of the website allele information page. The information page for a variation in an allele is pulled from an SNP database that is hosted on the website. General information for the allele is found at the top of the page and information such as protein residue changes can be found at the bottom of the page.

            Figure 7. The SNP Database gives information on the different alleles for a given gene, including the amino acid differences between alleles, under "Residue change," circled in yellow.

            Terms and Concepts

            • Genes
            • DNA
            • Mutation
            • Genetic disease
            • Nucleotides
            • RNA
            • Transcription
            • Translation
            • Amino acids
            • Codon
            • Hydrophilic
            • Hydrophobic
            • Allele


            • How does a gene become a protein?
            • In a given gene, what kind of DNA mutation would not change the protein that is made?
            • What makes some amino acids hydrophobic and others hydrophilic?
            • How common are mutations in the human genome? Is it very likely or very unlikely that your DNA carries any mutations?

            Resistance of the Race-Specific Type

            E ALLELISM

            Most genes for disease resistance are inherited independently of each other. When two or more genes are on the same chromosome, they may show varying degrees of linkage. In some cases the genes are either tightly linked or they are alleles, that is, they are at the same locus on a chromosome. Such tight linkage, or multiple allelism may restrict the number of genes that can be combined into one cultivar. In theory, a self-pollinated crop can be homozygous for only one gene at a locus. However, at several loci that were assumed to be multiple alleles for disease resistance, two or more of the alleles were recombined in coupling linkage, and they then behaved as one gene. In oats, stem rust resistance genes Pg-3 and Pg-9, assumed to be alleles, have been combined ( Koo et al., 1955 ). Similarly, in wheat the two alleles at the Lr14 locus have been combined ( Dyck and Samborski, 1970 ).

            Saxena and Hooker (1968) suggest that the Rp1 locus in maize, which may have as many as 14 different alleles for resistance to P. sorghi, consists of a series of tandem duplications of the original gene. These duplications have gradually differentiated to give resistance to different races of the rust. They suggest that the different alleles may consist of one or more combinations of the original gene and/or its modified duplicates. They also suggest the possibility of synthesizing a gene at one of these complex loci (e.g., the Rp1 complex has a large number of alleles with crossover values ranging from 0.10 to 0.37%) that would confer resistance to many cultures by systematically re-combining several of the alleles.

            Mayo and Shepherd (1980) , using a modified cis–trans test for functional allelism, found that several of the M alleles for resistance to flax rust were in fact separate, closely linked loci. They combined two of the M genes in the coupling phase where each of the genes functioned independently. Thus, it may be possible to combine three or more of the M genes in coupling to construct a complex resistance genotype.

            Some alleles at a locus, or closely linked genes, appear to be functionally related as they exhibit a similar phenotype. In wheat, each of the two alleles at the Lr14 locus for resistance to leaf rust gives a mesothetic infection type but to different races ( Dyck and Samborski, 1970 ). Also in wheat, each of the different alleles at the Sr9 locus for resistance to stem rust conditions a type 2 infection ( Roelfs and McVey, 1979 ). In oats the alleles or functionally related genes for resistance to stem rust, Pg-3 and Pg-9, also give resistance to crown rust ( McKenzie et al., 1968 ).

            Allelism, together with a scarcity of resistance genes, has been a particular problem in the development of stem rust resistant oat cultivars. Until recently it was assumed that there were only seven genes for resistance at three loci. It was suggested that these might involve three chromosomes belonging to a homoeologous series ( McKenzie et al., 1970 ). Two of the alleles at one locus were combined by Koo et al. (1955) , who suggested that this was a complex locus consisting of pseudoalleles. Several additional genes at different loci have more recently been found ( Martens et al., 1980 ).

            Genetic Dominance

            Mendel formulated the law of segregation as a result of performing monohybrid cross experiments on plants. The specific traits that he studied exhibited complete dominance. In complete dominance, one phenotype is dominant, and the other is recessive. Not all types of genetic inheritance, however, show total dominance.

            In incomplete dominance, neither allele is completely dominant over the other. In this type of intermediate inheritance, the resulting offspring exhibit a phenotype that is a mixture of both parent phenotypes. Incomplete dominance is seen in snapdragon plants. Pollination between a plant with red flowers and one with white flowers produces a plant with pink flowers.

            In codominance relationships, both alleles for a trait are fully expressed. Codominance is exhibited in tulips. Pollination that occurs between red and white tulip plants can result in a plant with flowers that are both red and white. Some people get confused about the differences between incomplete dominance and codominance.

            Is existence of different alleles for a gene a result of mutation? - Biology

            GENETICS 372 Winter 2000
            W. Fangman

            Definitions of Course Terms

            Allele One of the different forms of a gene or DNA sequence that can exist at a single locus.

            Aneuploid Not having the "correct" chromosome composition. An individual with an abnormal complement of chromosomes resulting from the absence of a chromosome(s) or the presence of an additional chromosome(s).

            Annealing Formation of double-stranded nucleic acid from single stranded forms.

            Apoptosis Programmed cell death (PCD) a process in which cellular DNA is degraded and the nucleus condensed then cell is then devoured by neighboring cells or phagocytes.

            Autosome Any chromosome other than the sex chromosomes or the mitochondrial chromosome.

            Blastocysts In mammals, the embryo at the 16-cell stage of development through the 64-cell satge when the embryo implants.

            Cancer genes Mutant alleles of naormal genes that lead to cancer

            Carcinogen Physical or chemical agent which induces cancer.

            Carrier In human genetics, an individual heterozygous for a mutant allele that generally causes disease only in the homozygous state. More generally, an individual who possesses a mutant allele but does not express it in the phenotype because of a dominant allelic partner thus, an individual of genotype Aa is a carrier of a if there is complete dominance of A over a.

            cDNA A duplex DNA where one strand is identical in sequence (except for T in place of U) and one is complementary to a particular RNA.

            cDNA libraries Libraries which store sequences copied into DNA from RNA transcripts typically these sequences carry only the exon information for making proteins.

            Centimorgan (cM) A unit of measure of ecombination frequency. One cM is equal to 1% chance that a marker at one genetic locus will be separated from a marker at a second locus due to crossing-over in a single generation.

            Chiasmata Observable regions in which nonsister chromatids of homologous chromosomes cross-over each other.

            Chi square ( c 2) test A statistical test to determine the probability that an observed deviation from the expected event or outcome occurs solely by chance.

            cis-acting locus Locus that affects the activity only of DNA sequences on the same molecule of DNA usually implies that the locus does not code for protein.

            cis configuration Two sites on the same molecule of DNA.

            Clone A group of cells or molecules that are identical by having arisen from a single ancestral cell or molecule.

            Chromosomes Self-replicating structures of cells that carry in their nucleotide sequences the linear array of genes.

            Complementarity The chemical affinity between specific nitrogenous bases as a result of their hydrogen bonding properties. The property of two nucleic acid chains having base sequences such that an antiparallel duplex can form where the adenines and thymines (or uracils) are apposed to each other, and the guanines and cytosines are apposed to each other.

            Complementation The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon.

            Chromatid One of the two side-by-side replicas produced by chromosome duplication.
            Codon A triplet of nucleotides that represents an amino acid or a termination (STOP) signal.

            Cross The deliberate mating of selected parents based on particular genetic traits desired in the offspring.

            Cross-over During meiosis, the breaking of one maternal chromosome, resulting in the exchange of corresponding sections of DNA, and the rejoining of the chromosome. The process can result in the exchange of alleles between chromosomes. Compare recombination.

            Cytoplasmic inheritance Inheritance via genes found in cytoplasmic organelles.

            Degenerate code A genetic code in which some amino acids may be encoded by more than one codon each.

            Denaturation The separation of the two strands of a DNA double helix, or the severe disruption of the structure of any complex molecule without breaking the major bonds of its chains.

            Domain of a protein A discrete continuous part of the amino acid sequence that can be equated with a particular function.

            Dominance The expression of a trait in the heterozygous condition.
            Downstream Sequences proceeding farther in the direction of transcription, for example, the coding region is downstream of the promoter.

            Endonuclease An enzyme that cleaves the phosphodiester bond within a nucleotide chain.
            Enzyme A protein that functions as a catalyst.

            Eukaryotes Organisms (ranging from yeast to humans) which have nucleated cells.

            Euploid Having the "correct" chromosome composition. Cells containing only complete sets of chromosomes.

            Exon Any segment of an interrupted gene that is represented in the mature RNA product. The protein-coding sequences of a gene.

            Exonuclease An enzyme that cleaves nucleotides one at a time from an end of a polynucleotide chain.

            Familial trait Any trait that is more common in relatives of an affected individual than in the general population could be due to genetic and/or environmental causes.

            Frameshift mutations Mutations that arise by deletions or insertions that are not a multiple of 3 bp they change the frame in which triplets are translated into protein.

            Gene The fundamental physical and functional unit of heredity, which carries information from one generation to the next a segment of DNA, composed of a transcribed region and a regulatory sequence that makes transcription possible.

            Genetic code The set of correspondences between nucleotide pair triplets in DNA and amino acids in protein.

            Genetic heterogeneity A similar phenotype being caused by different mutations. Most commonly used for a similar phenotype being caused by mutations in different genes. Allelic heterogeneity refers to different mutations in the same gene.

            Genetic markers Alleles of genes, or DNA polymorphisms, used as experimental probes to keep track of an individual, a tissue, a cell, a nucleus, a chromosome, or a gene.

            Genome The total genetic material of an organism, i.e. an organism's complete set of DNA sequences.

            Genotype The actual alleles present in an individual..

            Germ cells Specialized cells that form the reproductive organ where they ultimately undergo meiosis, thereby producing gametes that contain half the number of chromosomes as there body cells. Germ cells are responsible for transmitting genes to the next generation of an organism.

            Haploid A single set of chromosomes present in the egg and sperm cells of animals, in the egg and pollen cells of plants, and in stable or transient life cycle forms of some other organisms such as yeast.

            Haplotype A set of closely linked alleles (genes or DNA polymorphisms) inherited as a unit. A contraction of the phrase "haploid genotype."

            Heterozygous Having two different alleles at a given locus on a pair of homologous chromosomes.

            Heterogeneous trait see Genetic Heterogeneity

            Homologous chromosomes Chromosomes that pair with each other at meiosis.

            Homozygote An individual possessing a pair of identical alleles at a given locus on a pair of homologous chromosomes.

            Housekeeping gene Gene that is expressed in virtually all cells since it is fundamental to the any cell's functions.

            Hydrogen bond A weak bond involving the sharing of an electron with a hydrogen atom hydrogen bonds are important in the specificity of base pairing in nucleic acids and in the determination of protein shape.

            Hybridization The process of joining two complementary strands of DNA or one each of DNA and RNA to from a double-stranded molecule.

            Introns The DNA base sequences interrupting the protein-coding sequences of a gene. These sequences are transcribed into RNA but are cut out of the message before it is translated into protein.

            Inbred line A group of identical pure-breeding diploid or polyploid organisms, distinguished from other individuals of the same species by some unique phenotype or genotype, that are maintained by interbreeding.

            Karyotype The entire chromosome complement of an individual or cell, as seen during mitotic metaphase.

            Kilobase pair or kilobase (kb) 1000 base pairs of DNA or 1000 bases of RNA.

            Lawn Bacteria immobilized in a nutrient agar, used as a field to test for the presence of viral particles.

            Leader sequence The sequence at the 5' end of an mRNA that is not translated into protein.

            Library A set of cloned fragments together representing the entire genome, created then placed into storage.

            Ligase DNA ligase an enzyme that can rejoin a broken phosphodiester bond in a nucleic acid requires a 5' phosphate and a 3' OH.

            Linkage The proximity of two or more markers on a chromosome the closer together the markers are, the lower the probability that they will be separated by recombination, thereby increasing the probability that specific alleles will be inherited together

            Linkage group A group of genes chained together by linkage relationsships.

            Locus A specific location on a chromosome.

            Lod score The logarithm of the ratio of the odds that two loci are linked with a recombination fraction equal to or greater than 0 and less than 0.5 to the likelihood of independent assortment. Also called "Z."

            Marker same as Genetic marker

            Melting Denaturation of DNA.

            Missense mutation A single DNA base change which leads to a codon specifying a different amino acid.

            Model organisms Creatures used in genomic analysis because they have many genetic mechanisms in common with each other and with humans. These organisms lend themselves well to classical breeding experiments and direct manipulation of the genome.

            Morphogens Substances that define different cell fates in a concentration-dependent manner

            mRNA (messenger RNA) An RNA molecule, transcribed from a gene, from which a protein is translated by the action of ribosomes.

            Mutagen Any agent that is capable of increasing the mutation rate.

            Mutant allele An allele differing from the allele found in the standard, or wild type.

            Nonsense codon (also called STOP codon) Any one of three triplets (UAG, UAA, UGA) that cause termination of protein sysnthesis.

            Nonsense mutation (also called STOP mutation) Any change in DNA that causes a (termination) codon to replace a codon representing an amino acid.
            Nonsense suppressor (also called STOP suppressor) A gene coding for a mutant tRNA able to respond to one or more of the termination codons.

            Northern blotting Procedure to transfer RNA from an agarose gel to a nylon membrane.

            Null allele An allele that makes no gene product or whose product has no activity of any kind a deletion of a gene is necessarily a null allele.

            Null hypothesis The prediction that an observed difference is due to chance alone and not due to a systematic cause this hypothesis is tested by statisical analysis, and accepted or rejected.

            Oligonucleotides Small single-stranded segments of DNA typically 20-30 nucleotide bases in size which are synthesized in vitro.

            Oncogene An allele of a normal gene, called a proto-oncogene, that causes a cell to become cancerous.

            Open reading frame Streteches of codons in the same reading frame uninterrupted by STOP codons.

            Pedigree An orderly diagram of a family's relevant genetic features, extending back to at least both sets of grandparents and preferably through as many generations as possible.

            Penetrance The proportion of individuals with a specific genotype who manifest that genotype at the phenotype level.

            Phage Short for bacteriophage a virus for which the natural host is a bacterial cell. Literally "bacteria eaters."

            Phenotype Observable characterisics of an organism.

            Plaque In bacterial virus analysis, a clear area of a petri dish, devoid of bacterial cells, indicating the presence of viral particles.

            Plasmid Cytoplasmic, autonomously replicating extrachromosomal DNA molecule.

            Point mutation A change in a single base pair.

            Polarity An overall direction.

            Polymorphic site A chromosome site with two or more identifiable alleleic DNA sequences. Also called a polymorphic locus.

            Positional cloning The process where researchers obtain the clone of a gene without prior knowledge of its protein product or function it uses large-scale physical and formal genetic linkage maps to find specific genes.

            Primer Short, pre-existing oligonucleotide or polynucleotide cahin to which new DNA can be added by DNA polymerase.

            Prokaryote An organism without a nucleus eubacteria, archaebacteria, and blue-green algae.

            Promoter A region of DNA involved in binding of RNA polymerase to initiate transcription.

            Proto-oncogene A gene that can mutate to an allele, an oncogene, that causes a cell to become cancerous.

            Reading frame A sequence of sense codons such that each suceeding triplet generates the correct order of amino acids resulting in a polypeptide chain.

            Recessive allele An allele whose phenotypic effect is not expressed in a heterozygote.

            Recombinant DNA molecules A combinatin of DNA molecules of different origin that are joined experimentally.

            Recombination The formation of a new combination of alleles through independent assortment or crossing-over.

            Renaturation The reassociation of denatured complementary single strands of a DNA double helix.

            Restriction enzymes Proteins that recognize specific, short nucleotide sequences in DNA and catalyze cutting at those sites.

            Silent mutation Mutation in which the function of the protein product of the gene is unaltered.

            Somatic cells All the cells of an organism except those of the germ line.

            Suppression Changes that eliminate the effects of a mutation without reversing the original change in DNA.

            Suppressor mutation A mutation that counteracts the effects of another mutation. A suppressor maps at a different site than the mutation it counteracts, either within the same gene or at a more distant locus. Different suppressors act in different ways.

            Temperature-sensitive mutation A class of conditional mutations the mutant phenotype is observed in one temperature range and the wild-type phenotype is observed in another temperature range.

            Template strand The strand of the DNA double helix that is copied by base pair complementarity to make an RNA. The other, non-template strand of the DNA duplex has a sequence that is identical to the synthesized RNA (except in RNA, U replaces T).

            Trait Any detectable phenotypic variation of a particular inherited character.

            Transcription uni t The distance between sites of initiation and termination by RNA polymerase may include more than one gene.

            Trans configuration The configuration of two sites refers to their presence on two different molecules of DNA (chromosomes).

            Transfection of eukaryotic cells The acquisition of new genetic markers by incorporation of added DNA.

            Transformation of bacteria or yeast The acquisition of new genetic markers by incorporation of added DNA.

            Transformation of eukaryotic cells Their conversion to a state of unrestrained growth in culture, resembling or identical with the tumorigenic condition usually applied to mammalian cells.

            Transgenic organism One whose genome has been modified by externally applied new DNA a term applied to metazoans.

            Vector In cloning, the plasmid, phage, or yeast chromosomal sequences used to propagate a cloned DNA segment.

            Western blotting A technique in which proteins are separated by gel electrophoresis and transferred to a nylon sheet. A specific protein is then identified through its reaction with a labeled antibody.

            Wild type The genotype or phenotype that is found most commonly in nature or in the standard laboratory stock for a given organism.

            X-ray crystallography A technique for deducing molecular structure by aiming a beam of X rays at a crystal of the test compound and measuring the scatter of rays.