Compendium Reveiw- Topic 2 Genetics, Unit 1

Table of Contents:

I. Introduction

II. Chromosomes and Mitosis

III. Meiosis

IV. Chromosome Inheritance

V. Genotype and Phenotype

VI. Trait Crosses/Determining Phenotypes

1. Punnett Squares
2. Genetic Disorders

VII. DNA and RNA

1. DNA Structure and Function
2. Replication
3. RNA Structure and Function
4. Transcription and Translation

VIII. Genomics and DNA Technology

IX. Cancer

1. Characteristics of a Cancer Cell
2. Types of Cancer
3. Causes and Prevention of Cancer
4. Diagnosis
5. Treatment

XI. Conclusion

I. Introduction

What an exciting age we live in! The scientific community is making huge strides and discoveries in the area of genetics. These discoveries not only help us to gain a better understanding of our genetic inheritance and how our genes work, it helps to improve our lives as well. In July of this year my husband was diagnosed with cancer at the age of 36. He is currently, as I write this, undergoing chemotherapy. To help understand the battle we are facing, my husband and I have done a lot of research on his particular cancer. I was amazed to learn that the same diagnosis just 15 years ago would have been extremely grim. Today, he is encouraged with a prognosis of 97%. Cancer is no longer the death sentence it once was. The Human Genome Project has learned the sequence of the 3 billion bases found in the human genome, an accomplishment that just a few decades ago would not have been thought possible. So What exactly is genetics? What makes it possible for humans and other lifeforms to pass on specific traits from generation to generation? How can we treat and prevent genetic disease? What is the role of DNA? I will answer these questions and more in this compendium.

II. Chromosomes and Mitosis

Inside the nucleus of a cell is chromatin. Chromatin coils up into what we call chromosomes. Chromosomes consist of one long strand of DNA containing genetic information on an organism. Humans have 23 pairs of chromosomes. An individual receives one chromosome from its mother and one from the father. This is why chromosomes are are in pairs. The first 22 pairs are called autosomes and contain genes that control the traits in an individual. One pair of chromosomes controls gender. A picture, called a karyotype, of all 23 pairs can be taken with a special camera attached to a microscope.

A picture of a karyotype showing the 23 pairs of chromosomes. Page 378- Human Biology, Sylvia S. Mader

Cells spend much of their time in a state of interphase. This is the period when all the organelles carry out their various functions. When it comes time for the cell to divide, it grows larger and the DNA replicates, this happens before cell division. The process of cell division is called mitosis. There are 4 phases of mitosis, prophase, metaphase, anaphase, and telophase.

• During prophase the nuclear envelope fragments and disappears. The chromatin condenses into chromosomes. Microtubules that duplicated before prophase began, move apart and begin forming the spindle.
  
• The second phase of mitosis is metaphase. During metaphase the chromatid attach to spindle fibers at the centromere (the centromere holds the sister chromatid together). Spindle fibers stretch from one spindle pole to the other. Chromosomes line up at the center of the cell attached to these spindle fibers.
  
• During anaphase, the sister chromatids separate and move in opposite directions toward the spindle poles. Each pole will have the same number and type of chromosomes as the original cell.


• The forth and final phase is telophase. Here two daughter cells are forming. A nucleus surrounds the chromosomes and nucleoli return. The chromosomes will again become chromatin.
  

This picture gives an overview of mitosis. Page 381- Human Biology, Sylvia S. Mader

The cell cycle, including cell division, is vitally important to the health and well being of humans. Cells divide to pass on information coded in the chromosomes. Cell division also occurs to replace tissues that have worn out and to repair injuries.

III. Meiosis

The difference between mitosis and meiosis is that meiosis involves two nuclear divisions, resulting in four daughter cells. There are two stages of meiosis, meiosis I and meiosis II. Whereas mitosis is an exact duplicate of the cell, meiosis produces cells with the haploid, or half the number of chromosomes. These daughter cells are known as gametes. In humans the male gamete is a sperm and the female is an egg or ovum. It is important to note that the daughter cells of meiosis are not identical as they are in mitosis. Also, meiosis only occurs at certain times in the life cycle of reproductive age organisms.

The above graphic illustrates meiosis. Notice the two cell divisions. Page 385, Human Biology, Sylvia S. Mader

IV. Chromosome Inheritance

Ordinarily, a person will receive 22 pairs of autosomes carrying genes for particular traits ,and one pair of sex chromosomes. Sometimes people are born with too many or too few chromosomes. This can happen with the autosomes or the sex chromosomes. This most likely happens because of nondisjunction. Sometimes abnormal eggs have 24 chromosomes instead of 22. If this egg is fertilized the result is called trisomy, because one chromosome has three copies. This disrupts normal development. There are several trisomies that occur in humans, most do not result in survival. One trisomony with a reasonable chance of survival is Down Syndrome, or Trisomy 21. An individual with Down Syndrome has thee copies of chromosome 21.

I found this graphic at employees.csbsju.edu. It shows a close up of the extra chromosome.

V. Genotype and Phenotype

When a sperm fertilizes an egg, the resulting offspring acquires 23 chromosomes from its mother and 23 from its father. This way certain traits are inherited from both parents. The genes an individual inherits are referred to as the genotype. The physical characteristics resulting from these genes are the phenotype. The different forms of a gene that have the same position on a chromosome and affect the same trait are called alleles.

Some alleles are dominant and some are recessive. When designating alleles by letter, the dominant allele will be uppercase and the recessive will be lowercase. For example if we were looking at allele for the trait of a widow's peak, the dominant (widow's peak) would be represented by a W while the recessive (straight hairline) would be represented by a w.

VI. Trait Crosses/ Determining Phenotype

Because a child receives one chromosome from each parent, the child's phenotype may be different then that of the parents. If the child receives two dominant alleles for a particular trait, his genotype is homozygous dominant. Two recessive alleles result in a homozygous recessive genotype. Sometimes an individual receives on dominant and one recessive allele, this genotype is known as heterozygous.

• Punnett Squares

It is not always possible to know an individual's genotype, but it is possible to gain clues from his/her offspring. One helpful way of determining phenotypes is the Punnett Square. The alleles for the parents are placed on the top and left-hand sides of the square, and the grid is filled in with the resulting phenotypes. Below is a Punnett square showing cross between two heterozygous long wing flies and the possible phenotypes for their offspring. Although you can not see it in their phenotypes, both flies carry a recessive gene for vestigial wings, and there is a 25% chance that their off spring will inherit this trait.

Page from the virtual lab in the web links. www.mhhe.com/biosci/genbio/virtual_labs/BL_05/BL_0...

• Genetic Disorders

Sometimes certain disorders are passed through the genes. If a particular disorder is autosmal dominant a person having the alleles AA or Aa. will have the disorder. Sometimes a disorder is autosomal recessive. In this case parents can be carriers without actually having the disorder themselves. However, their offspring may inherit the disorder through the recessive gene. An example of an autosomal recessive disorder is Sickle-Cell Disease. In this disorder red blood cells do not have the normal shape, many of them are sickle shaped. People with Sickle Cell Disease suffer from anemia, poor circulation, and low resistance to infection.

An example of a sickle cell take from www.nslc.wustl.edu/sicklecell/sicklecell.html

VII. DNA and RNA

I have to say that this part of the unit proved to be the most difficult for me to understand. The concept of DNA and all the bases was a lot to wrap my head around. However, after reading the chapter twice and repeatedly going back to professor Frolich's Power Point, I think I finally have a basic idea of DNA, RNA, and how proteins are synthesized.

• DNA Structure and Function

DNA is short for deoxyribonucleic acid. DNA is the genetic information carried largely in the chromosomes. One stand of DNA is long and complex, holding three billion base pairs in humans. DNA has a beautiful double helix, ladder like, structure, with two sugar, phosphate backbones and paired bases filling in as the rungs of the ladder. The bases in DNA are Adenine (A), Thymine (T), Guanine (G), and Cytosine (C). Adenine is always paired with thymine and Guanine is always paired with Cytosine.

Genetic material needs to be able to do three things. It needs to replicate so it can be passed on to the next generation. Genetic material needs to store information for the organism. Lastly it should be able to undergo mutations in order to provide genetic variability. DNA does all these things.

• Replication

Replication occurs in the nucleus. When DNA replicates itself, the hydrogen bonds between the bases "unzip" and the bases break apart. Complimentary nucleotide bases that are found in the nucleus are fit into place with the aid of the enzyme DNA polymerase. Any breaks in the phosphate backbones are sealed by an enzyme. The resulting strands are identical.

Above is an overview of DNA replication. Notice that the new strand is identical to the old. Page 445. Human Biology, Sylvia S. Mader

• RNA Structure and Function

RNA stands for ribonucleic acid and is made up of nucleotides containing the sugar ribose. The bases in RNA are the same as in DNA with the exception of Uricil, which replaces Thymine. RNA also looks different than DNA in that it is single stranded. RNA is a helper to DNA. There are three types, ribosomal RNA (rRNA), messenger RNA (mRNA), and transfer RNA (tRNA). rRNA is produced in the nucleolus of a nucleus and joins with proteins to form subunits of ribosomes. Information is carried from DNA to the ribosomes by mRNA. tRNA transfers amino acids to the ribosomes. DNA serves as a template for these different types of RNA.

• Transcription and Translation

Transcription is the first step in what is called gene expression. In transcription, a strand of mRNA is formed that is complimentary to that particular portion of DNA. This is where the term transcription comes from, the mRNA is a "transcript" of a gene. To begin transcription, the DNA helix is opened by the mRNA polymerase. The RNA polymerase joins with the RNA nucleotides and the result is an mRNA molecule. Next the mRNA must be processed before entering the cytoplasm, this is when the mRNA "matures." During processing segments that the mRNA received from the DNA introns, which are not part of the gene, are removed. Exons are joined to form a mature mRNA.

Above is a graphic of transcription to mRNA. Here a particular gene codes for a particular protein. Page 449, Human Biology, Sylvia S. Mader.

The three-letter base code in mRNA is called a codon. There are 64 different mRNA codons. 61 of these triplet codes correspond to a particular amino acid, the other three are stop codons.

Ribosomes are part of the process of translation. This is where protein synthesis occurs. During translation, tRNA brings amino acids to the ribosomes. The ribosome consists of two subunits, the top unit is larger than the bottom. A strand of mRNA threads between the units. There is also a binding site in ribosomes for tRNA, tRNA carries the anticodon. Polypeptide sythesis consists of three steps, initiation, elongation, and termination. First, during initiation, an mRNA binds to a smaller subunit of the ribosome. The tRNA and the larger subunit come together with the smaller unit. During elongation the polypetide chain elongates one amino acid at a time. During termination, the ribosome will reach a stop codon and everything separates. What results is an amino acid chain that can fold up into a particular protein and catalyze reactions that control cell metabolism. It is important to know that not all mRNA carry the same genes from DNA. Different proteins are created from different sequences.

VIII. Genomics and DNA Technology

Professor Frolich mentioned in his presentation that the 21st century was going to be the era of genomics. The human genome has been sequenced by the Human Genome Project. Genomics helps scientists gain an understanding of our genetic heretage and how our genome compares to other species. Functional geneomics is looking to understand how all our genes work in cells and come to create a functional human being. Another benefit of geneomics is gene therapy, which has been used to treat certain disorders. There are ethical issues with genomics. For example how would it impact a person to learn certain things about their own genome? What would happen if that infomation was passed on to someone else? Some people also take issue with the idea of "designer children."

Cloning is another hotly debated issue in DNA technology. Cloning is the production of an identical DNA molecule, cell, or organism. This is done through asexual means. Dolly the sheep was an example of cloning.

IX. Cancer

Cancer is uncontrolled cell division. There are many different kinds of cancer but they all share characteristics that make them different from regular cells. What is interesting about cancer is that it is basically your own body turned against you. Oncology is the study of cancer.

• Characteristics of Cancer Cells

Cancer cells do not contribute to body function. Cancer cells also do not look like any of the types of cells that we discussed in the last topic, they are obviously abnormal. the nucleus of a cancer cell is abnormal and does not function properly. Even the chromosomes are abnormal. Whereas a normal cell will divide about 60-70 times in its lifetime, a cancer cell will divide an unlimited number of times, and it does not need growth factors to do this. Malignant cells will also pile on top of each other, forming tumors.

Carcinogenesis is the development of cancer and it happens in three stages. It begins with initiation when a single cell experiences a mutation and begins to divide repeatedly. The next stage is promotion, this is where a tumor develops. Progression is the third stage, where a cell gains an advantage and eventually has the ability to invade surrounding tissue. Metastasis occurs when cancer cells build new tumors far away from the original site. Cancer is able to travel to other areas of the body via the lymphatic system.

A diagram of tumor progression from the text book, page 405. Notice especially the cancer cells invading the lymphatic vessel. Human Biology, Sylvia S. Mader

• Types of Cancer

There are lots of different cancers, but they all fall into four basic categories. Cancers of epithelial tissues are called carcinomas. Sarcomas occur in muscles and connective tissues. Leukemias are cancers of the blood, while lymphomas occur in lymphatic tissue. The most common type of cancer in the USA is lung cancer. In women breast cancer is the most common, in men it is cancer of the prostate.

• Causes and Prevention

In some cases, like in my husband's situation, the cause of cancer is unknown. He has testicular cancer, a cancer that is less than one percent of all malignancies (percentage comes from mayoclinic.com). What physicians can tell us is that our son is now at an increased risk of contracting the disease because of heredity. Unfortunately my husband is adopted so we do not know if his father has cancer. Otherwise, my husband has none of the risks associated with testicular cancer. Reseachers have found links between genes and certain types of cancer.

Carcinogens are substances that cause cancer. Examples of some known carcinogens are tobacco smoke, radiation, pollutants, and certain vruses like HPV. Certain diets have been linked to cancer as well. Skin cancer is linked to UV rays from the sun.

• Diagnosis

Working for public health I have grown familiar with prevention programs, I worked in women's health for over six years and I can tell you that screening tests make a huge difference. Cancer can be treated if it detected early. Early detection is the goal with screening tests like pap smears, mammograms, and colonoscopies.

There are also warning signs that people can look for:

Change in bowel or bladder habits

A sore that does not heal

Unusual bleeding or discharge

Thickening or lump in breast or elsewhere

Indigestion or difficulty in swallowing

Obvious change in wart or mole.

Nagging cough or hoarseness.

I will tell you that my husband's symptoms where much more subtle, he did not have a lump or anything like that. However, because he was paying attention, he was able to detect the problem very early.

• Treatment

There are three standard therapies for cancer, surgery, chemotherapy, and radiation. Sometimes all three are used together to fight a particular cancer. Surgery is usually performed to remove the tumor. Radiation and chemotherapy are used to kill any cancer cells that may still be present. Bone marrow transplants are another form of treatment that is used in certain types of cancer. There are also new therapies for cancer treatment currently in clinical trials. Immunotherapy and gene therapy are two examples.

X. Conclusion

Again I will say that we live in exciting times. Breakthroughs in genetics and new discoveries will improve our lives as well as present new challenges. Greed often seems to get in the way when new treatments or medications are developed. We need to use the knowledge we gain from genetics wisely.

Sources:

Human Biology, Sylvia S. Mader

www.nslc.wustl.edu/sicklecell/sicklecell.html

www.mhhe.com/biosci/genbio/virtual_labs/BL_05/BL_0...

employees.csbsju.edu

turbosquid.com

mayoclinic.com