biology

· Required readings:

· Read

· Textbook Chapters 12, 13 (Reference is:

Lewis, R. 2018. Human Genetics, Concepts and Applications,13th ed. McGraw-Hill.

Content Guides

· What is a Mutation? Attached below

 

· Gene Mutations attached below

 

· Chromosomal Abnormalities attached below

WHAT IS MUTATION

Mutations are often called the “raw material of evolution.”  Evolution means change through time, and in terms of genetics, evolution means a  change in the frequency of alleles in the gene pool of a population. This change in allele frequency may occur by immigration or emigration of individuals into or out of the population. But the ultimate source of genetic variety is mutation, a change in the DNA of an allele.

A  mutation is an alteration in the structure of a gene or chromosome. It may involve duplications, deletions, or rearrangements of DNA. Mutations may be so small that they affect single base pairs of the DNA, or large enough to affect entire chromosomes. As you might expect, the vast majority of mutations are harmful, or even lethal. Occasionally, however, a mutation has a beneficial effect on the phenotype of an individual, which confers an evolutionary advantage over the other members of the population. If the individual gains a reproductive advantage over other members of the species, the frequency of occurrence of the mutation may increase rapidly in the population.

Mutations that involve whole chromosomes or large portions of chromosomes are termed  chromosomal mutations. Smaller mutations that occur on the level of individual genes are termed  gene mutations. Gene mutations involve the addition, deletion, or substitution of one or more nucleotides in a gene.

The genome contains a high degree of  duplication in DNA. There are many sequences that are repeated multiple times on chromosomes. One school of thought about these repeated sequences is that they are gene repositories that ensure the survival of genes down through the generations—a mutation in one of the copies will not affect the integrity of the other copies of that gene, which will continue to exist in the DNA of future generations.

Or the existence of many copies of genes may allow for the development of new genes in the course of evolution by means of different mutations to some of these copies, one of which might turn out to be beneficial. Multiple copies of genes allow for a lot more chance for modification without harm. A beneficial mutation, such as instructions for a slightly different respiratory pigment, may be advantageous to the individuals expressing it, and it may become an important new gene in the gene pool of the population.

Something that causes mutations is called a  mutagen. Certain chemicals (including many in tobacco) are mutagens, as are some types of radiation. Forms of radiation that contain more energy than visible light have the ability to cause changes in DNA structure.

· Ultraviolet (UV) light has been shown to cause unusual attachments along the DNA. Hence, the current justified obsession with sunscreen and safety concerns about tanning beds.

· Although  X-rays can be mutagenic, their diagnostic benefits can outweigh the risk of mutation; therefore X-rays continue to be used for the benefit of our medical and dental health (with precautions to minimize exposure to patients and health care workers).

· Gamma rays and  cosmic rays are also mutagenic. Astronauts and airline pilots get higher doses of these types of radiation at high altitudes, above the protection of the dense lower layers of Earth’s atmosphere.

· Radon is a form of radiation given off by radioactive minerals in the ground. In areas of the country known to have the presence of radon, house inspections for mortgages often require radon testing along with mitigation systems for homes with high levels.

It is important to determine what substances may be mutagenic to humans. Bruce Ames developed a test in the 1970s, called the  Ames test that is still used by chemical and pharmaceutical companies to assess the mutagenic potential of chemical products by observing the effects of the potential mutagen on bacterial colonies.

It is also important to remember that many mutations in DNA are subsequently repaired by protein complexes involved in  DNA repair. Researchers discovered that in the bacteria  E. coli, some damage caused by UV light could be repaired by an enzyme in a process called photoreactivation repair. In the last module you learned that occasional mistakes are made in DNA replication. Most of these mistakes are repaired by the proofreading enzyme DNA polymerase which backs up, cuts out the incorrect nucleotide, and replaces it with a correct nucleotide. Errors that escape notice may be detected and repaired by several other protein complexes involved in DNA repair.

Mutations are a natural part of life and you cannot avoid all mutagens. But, it is a good idea to reduce your exposure to as many known mutagens as you can. Don’t smoke, or if you already do, stop!

GENE MUTATIONS

Gene mutations involve changes in much smaller sections of DNA than chromosomal mutations. They usually affect only a single gene, and they often affect only one nucleotide pair. There are three basic types of gene mutations:  base substitutions (also called  point mutations) are potentially the least harmful since they do not cause a  frameshift mutation, the way that a  deletion or an  insertion does. The following example demonstrates the damage caused by frameshift mutations, using a sentence to represent a gene, and letters to represent nucleotides. Remember that the genetic code is written in groups of 3 nucleotides (codons).

Original Gene:

THE NEW CAT SAT AND HID ITS PAW

  Base Substitution (point mutation) – C replaced by a B:

THE NEW CAT SAT AND HID ITS PAW THE NEW BAT SAT AND HID ITS PAW

Deletion – W is lost:

THE NEW CAT SAT AND HID ITS PAW THE NEC ATS ATA NDH IDI TSP AW

Addition – O is inserted:

THE NEW CAT SAT AND HID ITS PAW THE ONE WCA TSA TAN DHI DIT SPA W

Notice how the words are all messed up after the frameshift mutations that result from the deletion or addition of one nucleotide.

Question: Which mutated sentence makes the most sense?  Answer: The base substitution only changed the meaning of one word, but the meaning of the sentence is changed, since bats do not have paws!

Deletions and additions may involve more than one nucleotide.  Question: When do they cause the least damage to the genetic code that follows them?  Answer: when they involve multiples of three nucleotides because then there is no frameshift mutation along the remaining length of the gene.

So far we have been talking about relative amounts of damage caused by a mutation; however a simple base substitution, like that in sickle cell anemia, is capable of having grave health effects, even though the mutation is so tiny. Proteins are complex molecules and any change to their amino acids may affect their folding patterns that create their 3D shapes and thereby change their abilities to carry out their functions.

CHROMOSAL ABNOMALITIES

All organisms have a set number of chromosomes in their genome. Cells with one set of chromosomes are termed  haploid. In humans, only the gametes have a haploid number of chromosomes (23 chromosomes). Cells with two sets of chromosomes are termed  diploid. In humans, all other cells (somatic cells) are diploid, because they have two sets of 23 chromosomes, for a total of 46 chromosomes. Some types of chromosomal mutations involve abnormalities in chromosome number. Loss of a chromosome is uncommon since it is usually lethal and extra copies of chromosomes can sometimes be tolerated.

Aneuploidy is the condition of having an abnormal number of chromosomes. The gain or loss of one chromosome is the most common form. Aneuploidy results from  nondisjunction, which is the failure of homologous chromosomes to separate during the first or second meiotic division. Nondisjunction results in aneuploid gametes, which may join normal haploid gametes to produce monosomic or trisomic zygotes.

Monosomy, in which one chromosome is missing, is usually a lethal condition.

Turner syndrome – XO – with only one X sex chromosome (45,X) is the only non-lethal type of monosomy in humans. YO monosomy is lethal.

A summary of some viable abnormal sex chromosome numbers:

· XO – Turner’s Syndrome – short female, usually infertile

· XXY – Klinefelter’s Syndrome – tall male, usually infertile

· XXX – Triple X Syndrome – tall female, fertile

· XYY – XYY Syndrome – tall male, fertile

Trisomy results from the addition of an extra chromosome following nondisjunction. A common example of trisomy in humans is  Down syndrome, sometimes called trisomy 21. In 95% of Down syndrome cases, the extra chromosome 21 is caused by nondisjunction, and does not run in families. The mistake in meiosis almost always occurs in the formation of the ovum, and is thought to result from the advanced age of oocytes that began their development before the mother’s birth.  Familial Down syndrome is responsible for the other 5% of cases, and has a completely different cause, unrelated to the age of the mother; it is a translocation (explained below) of chromosome 21.  This syndrome begins as a spontaneous mutation, but then it can be passed to future generations since the translocation can be passed down to the gametes.

Chromosomal mutations that involve structural changes in chromosomes include deletion, duplication, inversion, and translocation. These mutations are caused by breaks in chromosomes. Broken chromosomes have “sticky” ends that may join with the “sticky” ends of the same chromosome or other broken chromosomes.

Deletion involves the loss of a part of a chromosome.  Cri-du-chat syndrome results from the loss of a small part of chromosome 5.

Duplication can result from a mistake during replication of the chromosome, or from unequal crossing over during synapsis.

Inversion occurs when a segment of the chromosome detaches, flips over, and then reattaches so that the affected genes are in backwards order. Individuals with inversions may be normal, but their gametes may be abnormal.

Translocation involves the movement of part of a chromosome to a new location. In  familial Down syndrome, short ends of chromosomes 14 and 21 have broken off and are lost (fortunately none of the lost genes are necessary for survival). The two “sticky” ends attach to form a large chromosome that is a combination of the two chromosomes. An individual with this transformation has a normal phenotype. During gamete formation, however, four different types of gametes will be produced: one normal, one lethal, one carrier, and one that displays trisomy 21—the familial type of Down syndrome, which represent 5% of all cases.

Assignment 1 - 1 page

Please view the case studies on the following websites (links below). Choose the one that interests you the most.

1. Genome BC Case Studies  (view both the Student Worksheet and the Teacher Key and Notes)

2. GWU Case Studies

3. Clinical Case Studies

First explain why you chose this genetic disorder. Then present a summary of the case study for your classmates, including some of the following:

· the genetic mutation(s) that cause(s) the disorder

· mode of inheritance

· the symptoms of the disorder

· treatments for the disorder

· your personal comments about the disorder

Assignment 2 - 1 ½ papes

Copy the following question, add your answer, and submit them below in one attached document.

1. Explain different ways researchers might determine the location of a mutation in the human genome that is responsible for a particular disorder. Browse through some of the disorders in the link below and notice differences among the three groups: Types of Genetic Disorders

a. Describe different types of genetic disorders.

b. Discuss methods used by early geneticists to locate mutations (think about what tools were available).

c. Then discuss some more modern methods, including the use of knockout mice (see the link below to a fact sheet). 

Knock out Mice

Assignment 3 –

Case Study Click on the following link to view a case study about cystic fibrosis:

Case Study - Sometimes it  is All in the Genes

(Attached in another file) then fill in the the attached case study form. Please use references from the required list provided in this assignment and two other relevant references