CK-12 Life Science

by CK-12 Foundation

  Figure 6.10

  A pedigree chart shows all the phenotypes for a particular trait in the family. This pedigree chart traces back the occurrence of hemophilia in the British royal family. Those individuals with boxes around them are either female carriers of the trait or males afflicted with the trait.

  Many genetic disorders are recessive, meaning that an individual must be homozygous for the recessive allele to be affected. Sometimes these disorders are lethal (deadly), however, heterozygous individuals (unaffected individuals with one dominant allele and one recessive allele) survive. This allows the allele that causes the genetic disorder to be maintained in a population's gene pool. A gene pool is the complete set of unique alleles in a species or population. A mutation is a change in the DNA sequence. New mutations are constantly being generated in a gene pool.

  Pedigree Analysis

  A pedigree is a chart which shows the inheritance of a trait over several generations. A pedigree is commonly created for families, and it outlines the inheritance patterns of genetic disorders. Figure below shows a pedigree depicting recessive inheritance of a disorder through three generations. Scientists can tell the genetics of inheritance from studying a pedigree, such as whether the trait is sex-linked (on the X or Y chromosome) or autosomal (on a chromosome that does not determine sex), whether the trait is inherited in a dominant or recessive fashion, and possibly whether individuals with the trait are heterozygous or homozygous.

  Figure 6.11

  In a pedigree, squares symbolize males, and circles represent females. A horizontal line joining a male and female indicates that the couple had offspring. Vertical lines indicate offspring which are listed left to right, in order of birth. Shading of the circle or square indicates an individual who has the trait being traced. The inheritance of the recessive trait is being traced. A is the dominant allele and a is recessive.

  Chromosomal Disorders

  Some children are born with genetic defects that are not carried by a single gene. Instead, an error in a larger part of the chromosome or even in an entire chromosome causes the disorder. Usually the error happens when the egg or sperm is forming. One common example is Down syndrome (Figure below). Children with Down syndrome are mentally disabled and have collection of recognizable physical deformities. Down syndrome occurs when a baby receives an extra chromosome from one of his or her parents. Usually a child would have one chromosome 21 from its mother and one chromosome 21 from its father. But in an individual with Down syndrome, there are three copies of chromosome 21. Down syndrome is therefore also known as Trisomy 21.

  Figure 6.12

  A child with Down syndrome.

  Another example of a chromosomal disorder is Klinefelter syndrome, in which a male inherits an extra “X” chromosome. These individuals have underdeveloped sex organs and elongated limbs, and have difficulty learning new things. Outside of chromosome 21 and the sex chromosomes, most embryos with extra chromosomes do not even make it to the fetal stage. Because chromosomes carry many, many genes, a disruption of a chromosome potentially causes severe problems with development of the fetus.

  Besides diseases caused by duplicated chromosomes, other chromosomal disorders occur when the structure of a chromosome is disrupted. For example, if a tiny portion of chromosome 5 is missing, the individual will have cri du chat (cat’s cry) syndrome. These individuals have misshapen facial features and the infant’s cry resembles a cat’s cry.

  Lesson Summary

  Some human traits are controlled by genes on the sex chromosomes.

  Human genetic disorders can be inherited through recessive or dominant alleles, and they can be located on the sex chromosomes or autosomes.

  Changes in chromosome number can lead to disorders like Down syndrome.

  Review Questions

  How many chromosomes do you have in each cell of your body?

  How is Down's syndrome inherited?

  A son cannot inherit colorblindness from his father. Why not?

  One parent is a carrier of the cystic fibrosis gene, while the other parent does not carry the allele. Can their child have cystic fibrosis?

  Further Reading / Supplemental Links

  http://www.articlesbase.com/health-articles/what-is-haemophilia-412305.html

  http://geneticdisorderinfo.wikispaces.com/

  http://www.hhmi.org/biointeractive/vlabs/cardiology/index.html

  Vocabulary

  autosomes

  The chromosome other than the sex chromosomes.

  carrier

  A person who is heterozygous for a recessive genetic disorder; the person does not have the disease but can pass the disease allele to the next generation.

  sex-linked trait

  A trait that is due to a gene located on a sex chromosome, usually the X-chromosome.

  Points to Consider

  Human cloning is illegal in many countries. Do you agree with these restrictions?

  Why would it be helpful to know all the genes that make up human DNA?

  It may be possible in the future to obtain the sequence of all your genes. Would you want to take advantage of this opportunity? Why or why not?

  Lesson 6.4: Genetic Advances

  Lesson Objectives

  Explain how clones are made.

  Explain how vectors are made.

  Explain what sequencing a genome tells us.

  Describe how gene therapy works.

  Check Your Understanding

  What part of the cell contains the genetic material?

  What are the base pairing rules for DNA?

  Introduction

  Since Mendel’s time, there have been rapid advances in the understanding of genetics. As scientists understand better how DNA works, they can develop technologies that allow us to reveal the genetic secrets encoded in our DNA and even alter an organism’s DNA. Genetic engineering (or biotechnology or DNA technology) has helped us better understand and predict the inheritance of genetic diseases, produce new medicines, and even produce new food products. DNA technology has also made an impact on fighting crime. Because DNA is unique to an individual, the DNA in just a few hairs at a crime scene can help identify a criminal. This technology, known as DNA fingerprinting, has also helped innocent imprisoned people to appeal their case and clear their names. DNA technology has revolutionized not only criminal justice, but also many other aspects of our lives.

  Recombinant DNA

  Recombinant DNA is the combination of DNA from two different sources. It is useful in gene cloning and in identifying the function of a gene, as well as producing useful proteins. Human insulin for treating diabetes has been produced through recombinant DNA methods. In this process, a gene of interest (or piece of DNA of interest) is placed into a host cell, such as a bacterium, so the gene can be copied (and cloned) and the protein that results from that gene can be produced.

  To place the gene of interest into a host cell, a vector, or carrier molecule, is needed to the carry foreign DNA into the host cell. Bacteria have small accessory rings of DNA in the cytoplasm, called plasmids. When putting foreign DNA into a bacterium (a host cell), the plasmids are often used as a vector. Viruses can also be used as vectors.

  The first step of making recombinant DNA involves a restriction enzyme that cuts the vector and the foreign (exogenous) DNA. Restriction enzymes cut DNA at specific sequences, such as GAATTC as shown in Figure below . There are more than 3,000 known restriction enzymes, most cutting the DNA at a unique sequence. This reaction results in the plasmid opening up a gap with “sticky ends,” which can attach with the complimentary base pairs on the sticky ends of the foreign DNA. Then the enzyme DNA ligase seals the foreign DNA in its new place inside the plasmid. These altered plasmids are introduced back into the bacteria, a process called transformation (Figure below). The bacteria will express the foreign gene.

  Figure 6.13

  Restriction enzymes cut DNA at specific sequences, in this example the sequence GAATTC." The enzyme cuts be
tween the G and A on each strand, producing overhanging sticky ends.

  Figure 6.14

  This image shows a line drawing of a plasmid. The plasmid is drawn as two concentric circles that are very close together, with two large segments and one small segment depicted. The two large segments (1 and 2) indicate antibiotic resistances usually used in a screening procedure, and the small segment (3) indicates an origin of replication. The resulting DNA is a recombinant DNA molecule.

  One application of recombinant DNA technology is producing the protein insulin, which is needed to treat diabetes. Previously, insulin had been extracted from the pancreases of animals. Through recombinant DNA technology, bacteria were created that carry the human gene which codes for the production of insulin. These bacteria become tiny factories that produce this protein. A step-by-step depiction of the cloning of the insulin gene is shown below in (Figure below).

  Figure 6.15

  A step-by-step depiction of the cloning of the insulin gene. The plasmid is opened up with restriction enzymes and the gene of interest (human cDNA) is inserted into the plasmid with complementary linkers, producing the recombinant plasmid. The plasmid is transfected into bacterial cells, where the human protein is produced.

  Cloning

  Cloning is the process of creating an exact replica of an organism. The clone’s DNA is exactly the same as the parent’s DNA. Bacteria and plants have long been able to clone themselves through processes of asexual reproduction. In animals, however, cloning does not happen naturally.

  Animals can now be cloned in a laboratory, however. In 1997, a sheep named Dolly was the first mammal ever to be successfully cloned. The process of producing an animal like Dolly starts with a single cell from the animal that is going to be cloned. In the case of Dolly, cells from the mammary glands were taken from the adult that was to be cloned. These cells are called somatic, meaning they come from the body and are not gametes like sperm or egg. Remember that somatic cells have a diploid number of chromosomes. Next, the nucleus was removed from this cell. The nucleus was placed in a donor egg that had already had the nucleus removed. The new cell then divided after the stimulation of an electric shock, and development proceeded normally just as if the embryo had formed naturally. The resulting embryo was implanted in a surrogate mother sheep, where it continued its development. This process is shown in Figure below.

  Figure 6.16

  To clone an animal, a nucleus from the animals cells are fused with an egg cell (from which the nucleus has been removed) from a donor.

  Cloning is not always successful, though. Most of the time, this cloning process does not result in a healthy adult animal. The process has to be repeated many times until it works. In fact, 277 tries were needed to produce Dolly. This high failure rate is one reason that human cloning is banned in the United States. In order to produce a cloned human, many attempts would result in the surrogate mothers experiencing miscarriages, stillbirths, or deformities in the infant. There are also many additional ethical considerations related to human cloning.

  Human Genome Project

  A person’s genome is all of his or her genetic information; in other words, the human genome is all the information that makes us human. The Human Genome Project (Figure below) was an international effort to sequence all 3 billion bases that make up our DNA and to identify within this code the over 20,000 human genes. Scientists also completed a chromosome map, identifying where the genes are located on each of the chromosomes. The Human Genome Project was completed in 2003. Though the Human Genome Project is finished, analysis of the data will continue for many years.

  Figure 6.17

  To complete the Human Genome Project, all 23 pairs of chromosomes in the human body were sequenced. Each chromosome contains thousands of genes. This is a karyotype, a visual representation of an individuals chromosomes lined up by size.

  There are many exciting applications of the Human Genome Project. The genetic basis for many diseases can be more easily determined, and now there are tests for over 1,000 genetic disorders. The National Institutes of Health, the United States government’s premiere biomedical research community, is also looking for ways to reduce the costs of sequencing so that people can have a map of their individual genome. Although some disorders are caused by a single gene, many other illnesses are caused by a combination of several genes and a person’s lifestyle. Analysis of your own genome could determine if you are at risk for specific diseases. Knowing you might be genetically prone to a certain disease would allow you to better seek preventive lifestyle changes and medical screenings.

  A genetic map shows the location (or loci) of a gene on a chromosome. Genetic maps are important tools to help researchers understand genes and genetic diseases. Knowing where genes are in relation to other genes and knowing the order of genes on a chromosome is an important aspect of human genetics. The frequency of recombination (crossing-over during prophase I of meiosis) allows geneticists to estimate the distance between loci. Because crossing-over occurs relatively rarely at any location along the chromosome, the frequency of recombination between two locations depends on their distance. The farther apart genes are on the same chromosome, the more likely there is to be a cross-over event between them. The likelihood of a cross-over event between two closely located genes (said to be linked) is small.

  Gene Therapy

  Gene therapy is the insertion of genes into a person’s cells to cure a genetic disorder. There are two main types of gene therapy; one done inside the body and one done outside the body. In ex vivo gene therapy, done outside the body, cells are removed from the patient and the proper gene is inserted using a virus as a vector. Then the modified cells are placed back into the patient. One of the first uses of this type of gene therapy was in the treatment of a young girl with a rare genetic disease, Adenosine deaminase deficiency, or ADA deficiency. People with this disorder are missing the ADA enzyme, which breaks down a toxin called deoxyadenosine. If the toxin is not broken down, it accumulates and destroys immune cells. As a result, individuals with ADA deficiency do not have a healthy immune system to fight off infections. In the gene therapy treatment for this disorder, bone marrow stem cells were taken from the girl’s body and the missing gene was inserted in these cells outside the body. Then the modified cells were put back into her bloodstream. This treatment proved sufficient to restore the function of her immune system, but only with continual repeated treatments.

  During in vivo gene therapy, done inside the body, the vector with the gene of interest is introduced directly into the patient and taken up by the patient’s cells. The vector is inserted where the gene product is needed. For example, cystic fibrosis gene therapy is targeted at the respiratory system, so a solution with the vector can be sprayed into the patient’s nose. Recently in vivo gene therapy was also used to partially restore the vision of three young adults with a rare type of retinal disease that is congenital, meaning present at birth.

  Biotechnology in Medicine and Agriculture

  There are many applications of genetic information, including applications in medicine and agriculture. These applications show daily the significance of biotechnology, and the impact biotechnology has on our society.

  Medicine

  As mentioned above, one application of recombinant DNA technology is producing the protein insulin. Using biotechnological techniques, the specific gene sequence that codes for human insulin was introduced into the bacteria E. coli. The transformed gene altered the genetic makeup of the bacterial cells, such that in a 24 hour period, billions of E. coli containing the human insulin gene resulted, producing human insulin to be administered to patients. Recombinant DNA technology has allowed mass quantities of insulin to be produced, treating the growing population that relies on this protein.

  Though the production of human insulin by recombinant DNA procedures is an extremely significant event, many other aspects of DNA technology are beginning to become reality. In medicine, modern biotechnology p
rovides significant applications in such areas as pharmacogenomics, genetic testing (and prenatal diagnosis), and gene therapy. These applications use our knowledge of biology to improve our health and our lives. Many of these medical applications are based on the findings of the Human Genome Project.

  Agriculture

  Biotechnology has also led scientists to develop useful applications in agriculture and food science. These include the development of transgenic crops - the placement of genes into plants to give the crop a beneficial trait. Benefits include:

  Improved yield from crops.

  Reduced vulnerability of crops to environmental stresses.

  Increased nutritional qualities of food crops.

  Improved taste, texture or appearance of food.

  Reduced dependence on fertilizers, pesticides and other agrochemicals.

  Crops are obviously dependent on environmental conditions. Drought can destroy crop yields, as can too much rain or floods. But what if crops could be developed to withstand these harsh conditions? Biotechnology will allow the development of crops containing genes that will enable them to withstand harsh conditions. For example, drought and excessively salty soil are two significant factors affecting crop productivity. But there are crops that can withstand these harsh conditions. Why? Probably because of that plant's genetics. So scientists are studying plants that can cope with these extreme conditions, trying to identify and isolate the genes that control these beneficial traits. The genes could then be transferred into more desirable crops, with the hope of producing the same phenotypes in those crops.