Biology 140 – Human Biology Lab Notebook – Human Inheritance Laura Ambrose Luther College © 2012 113 | P a g e Contents Human Inheritance ................................................................................................................................... 115 Introduction .......................................................................................................................................... 115 Learning Goals................................................................................................................................... 115 Learning Objectives ........................................................................................................................... 115 Checklist of topics covered and in-lab activities to complete .......................................................... 115 Background ........................................................................................................................................... 116 Genetics is about terminology .......................................................................................................... 116 Punnett Squares ................................................................................................................................ 118 Readings ................................................................................................................................................ 119 Pre-lab Questions.................................................................................................................................. 119 Lab activities and worksheets ............................................................................................................... 120 Karyotypes and Genetic Disorders.................................................................................................... 120 Genetic Traits .................................................................................................................................... 126 PTC Sensitivity: Linking genes and traits ........................................................................................... 133 Tracking two traits – Two gene cross................................................................................................ 135 Blood Type – Multiple Allele Inheritance and Co-dominance .......................................................... 138 Sex-linked traits – Colour Blindness .................................................................................................. 140 Incomplete Dominance – snapdragons ............................................................................................ 143 Human Height – Multifactorial Inheritance ...................................................................................... 145 Lab assessments.................................................................................................................................... 145 In lab.................................................................................................................................................. 145 Homework......................................................................................................................................... 145 Study guide ....................................................................................................................................... 146 Resources .............................................................................................................................................. 146 114 | P a g e Human Inheritance Introduction The study of inheritance is the study of how traits are passed from one generation to the next. Recall that meiosis separates pairs of chromosomes and randomly puts them into gametes. Sexual reproduction fuses the nucleus from one parent with the nucleus from the other parent, bringing chromosomes back together into pairs. The traits that we have are the expression of genes on the chromosomes. Learning Goals To introduce basic patterns of genetic inheritance To introduce the Punnett Square as a tool for predicting outcomes of genetic crosses Learning Objectives 1. After an introduction to the terminology of genetics and a discussion on basic patterns of inheritance, students will understand how single-gene traits are inherited. 2. After a demonstration and explanation of Punnett Squares, students will be able to predict outcomes of genetic crosses. 3. After a discussion and demonstration, students will understand more complex patterns of inheritance. Checklist of topics covered and in-lab activities to complete - Karyotype activities - Inventory of traits - PTC case study - Two gene cross, blood types, sex-linked traits, multifactorial inheritance 115 | P a g e Background Staring at the family picture on the wall, Marcy again noticed how small Lucy was compared to all of the other people in her family. Lucy was at least 6 inches shorter than the shortest sibling. Marcy and her brothers used to tease Lucy about not really being part of the family, but it was clear looking at the family pictures that Lucy was very much part of the family. Lucy’s eyes were very light blue, just like her mother and grandfather, and her skin was dotted with the same freckles as her father. The similarities continued with the pointy hairline, rounded earlobes, long fingers, and those dimples that everyone thought was so adorable when Lucy was born. That cuteness, combined with Lucy being the baby of the family, was probably what led Marcy and her brothers to torment her about her height. The most important trait that Lucy inherited from her parents was patience to deal with incessant teasing from siblings! With all those similarities, why was Lucy so very much shorter than the rest of the people in the family? What other factors interacted with her genes to cause her to stop growing before everyone else? Genetics is about terminology There are a lot of terms in genetics that seem very unfamiliar. It is important to understand these terms in order to be able to understand the patterns of inheritance. Recall that the DNA in the human body cells is organized into 46 chromosomes, which is further organized into 23 homologous pairs. Contained within the DNA are genes, which are specific instructions for making specific proteins. The proteins are then involved in building structures or directing biochemical reactions. A person who studies genetics looks at the genes that determine the traits that we can see or measure. Inheritance is the study of how these genes and traits are passed from one generation to the next, including predicting the outcomes of genetic crosses. An allele is an alternative form of a gene. For example, humans have genes for pigment in eyes and there are different forms of the gene that relate to the different colours of pigments that the gene can produce, such as brown pigment, blue pigment, gold pigment, or green pigment. Sex chromosomes contain genes that have instructions for building and operating the sex organs that determine the sex (male or female) of a person. Autosomes are the chromosomes that contain genes that do not control the sex of the individual. Recall that genes come in pairs, because chromosomes come in pairs, and that the genes are instructions for proteins that determine the trait a person has. Also recall that the alleles in the pair may, or may not, be the same. If the alleles are the same, the pair is called homozygous. The prefix homo- means the same; -zygous refers to the zygote, or diploid, state. If the alleles are different, the pair is called heterozygous. The prefix hetero- means different. Alleles are called dominant or recessive, based on how the genes are expressed when they are together. A dominant allele is expressed even when the recessive allele is present. A recessive allele is only expressed if there are two recessive alleles in the gene pair. Genes are usually represented by single letters with an uppercase 116 | P a g e letter used for the dominant allele and a lowercase letter for the recessive allele. There are three possible combinations of dominant and recessive alleles: dominant-dominant dominant-recessive recessive-recessive Homozygous dominant Heterozygous Homozygous recessive Genotype AA Aa aa Phenotype Brown eyes Brown eyes Blue eyes When geneticists are studying the genes a person has, they are looking at that person’s genotype. When doctors are looking at the traits a person has, they are looking at that person’s phenotype. The phenotype refers to the traits that we can see and measure, such as eye pigmentation, cholesterol levels, or the presence of polyps in the colon. The genotype is the genes that determine those traits. A single-gene cross is when we look at one trait at a time to determine the possible outcomes of a cross between two individuals. For example, we might try to figure out the possible outcomes for the offspring for a father that is colour blind and a mother that is not colour blind. A hybrid is another way to describe the heterozygote. A carrier also describes the heterozygote. The term carrier usually refers to the situation where a person carries the recessive allele for a disease but does not know they carry the recessive allele because it is masked by the dominant allele. A dihybrid is the situation where a person is heterozygous for two traits. A dihybrid cross is a cross between two individuals that are both heterozygous for two traits (TtAa and TtAa). A genotypic ratio is a summary of the genotype results of the Punnett Square. A phenotypic ratio is a summary of the phenotype results of the Punnett Square. A karyotype is a picture of the chromosomes from a cell. A karyotype is created when cells are sampled from an area of the body that is undergoing division. Recall that cells that are actively dividing have chromosomes that are condensed and visible under a light microscope. The cells are treated to release the condensed chromosomes from the nucleus and the chromosomes are photographed. The chromosomes are organized in homologous pairs from largest to smallest, with the sex chromosomes set at the end. Doctors use the karyotype to determine if a person has a genetic abnormality related to chromosome structure or number. 117 | P a g e In this example, you can see there are 46 chromosomes and it comes from a human female. Geneticists are compiling a list of human disorders that are related to chromosomal abnormalities. Here are a few examples. Chromosomal Makeup 46 XX 46 XY 13 trisomy 18 trisomy 21 trisomy XXY XO Clinical Conditions Female (normal) Male (normal) D1 syndrome E syndrome Down’s syndrome Klinefelter’s syndrome Turner’s syndrome Punnett Squares A Punnett Square is a tool used to predict the possible outcomes of a cross between two individuals. In order to draw a Punnett Square, you need to know the following information: - The genotypes and phenotypes of the parents Whether the trait is autosomal or based on the sex chromosomes Whether the trait is dominant or recessive With this information you can determine the gametes of the parents, draw the Punnett Square, and write genotypic and phenotypic ratios to explain the outcome. The information you need to draw the Punnett Square is usually written into a word problem. Read through the following example. 118 | P a g e Cystic fibrosis (CF) is a recessive trait. Not having CF (A) is dominant over having CF (a). A man who is a carrier for CF mates with a woman that does not have CF and is not a carrier for CF. Draw the Punnett Square for this cross. Indicate the phenotypes, genotypes, and gametes of the parents. Write out the genotypic and phenotypic ratios. Phenotypes Genotypes Gametes Male Does not have CF Aa A or a Female Does not have CF AA A only Punnett Square A A A AA AA a Aa Aa Genotypic Ratio: 2 AA: 2 Aa: 0 aa Phenotypic Ratio: 4 No CF : 0 CF It is clear from this cross that there is a 0% chance of having a child with Cystic Fibrosis. Readings In order to be able to complete your lab on time and get the most out of it, complete these readings and view the videos or animations before your lab period. o o o o Textbook Chapter 20 Gregor Mendel’s work with pea plants (animation): http://www.dnaftb.org/1/animation.html Here are some practice genetics problems. They are an online activity. http://biology.clc.uc.edu/courses/bio105/geneprob.htm Here are some tips for solving genetics problems: http://www.ableweb.org/volumes/vol21/mini.1.schwab.pdf Pre-lab Questions 1. 2. 3. 4. What traits do you have that you can see in your parents? What traits to you hope you will pass on to your offspring? What traits do you hope you will NOT pass on to your offspring? A dog breeder wanted puppies that were light brown and had long tails. Using the tools you are learning about in this lab, how might the breeder figure out which parents to mate? 119 | P a g e Lab activities and worksheets As humans, we are often fascinated with our heredity. Starting when we are very young we are told “You look just like your mother” or “I see you have your father’s eyes”. As we get older we start to wonder “Will I lose my hair like my grandfather” or “Will I get the same wrinkles as my mother”. Sometimes behaviours are associated between generations, such as having a fiery temper or a love of reading. The study of inheritance is concerned only with those traits that are genetic, or based in the DNA that makes up our genes. Karyotypes and Genetic Disorders 1. How many chromosomes are found in genetically normal human cells? 2. What sex chromosomes are found in a genetically normal human male? 3. What sex chromosomes are found in a genetically normal human female? Look at the following karyotypes. Beside each karyotype indicate: 1) how many chromosomes are present 2) which sex chromosomes are present 3) whether or not the genetic state is normal. If the genetic state is not normal, use the table in the background section to determine what disorder the person has. 120 | P a g e Example 1 121 | P a g e Example 2 122 | P a g e Example 3 123 | P a g e Example 4 124 | P a g e Example 5 This activity is a TA Checkpoint. Have your karyotypes checked and initialled by a lab Teaching Assistant. 125 | P a g e Genetic Traits We are often curious about the traits we have, where they came from, and how they are going to be passed down to our offspring. Many human traits are controlled by single genes in our genome. Answer the following questions and then figure out how common the traits are in your group. Adapted from “Alike But Not The Same” in Human Genetic Variation, NIH Curriculum Supplement Series 1999. http://science-education.nih.gov An Inventory of My Traits - Survey What combination of these traits do you have? Complete the survey to find out. 1. I have detached earlobes Yes No 2. I can roll my tongue Yes No 3. I have dimples Yes No 4. I am right-handed Yes No 5. I have freckles Yes No 6. I have naturally curly hair Yes No 7. I have a cleft chin Yes No 8. I have allergies Yes No 9. I cross my left thumb over my right when I clasp my hands together Yes No 10. I can see the colors red and green (I am not color blind) Yes No 11. The hairline on my forehead is straight. Yes No 12. I am a: Male Female 126 | P a g e An Inventory of My Traits - Data Table How many people in your group have each trait? Fill in the data table below by counting the number of people who marked “yes” and the number of people who marked “no” for each trait. Trait Detached earlobes Yes No Tongue rolling Dimples Right-handed Freckles Naturally curly hair Cleft chin Allergies Cross left thumb over right See the colors red and green Have a straight hairline 127 | P a g e An Inventory of My Traits - Data Table Draw a bar graph to show how many people in the group have each trait. It might help to turn your paper sideways and draw the X axis along the long edge of the paper. 128 | P a g e 129 | P a g e The Case Study – To the Bitter End: A Case Examining the Genetics of PTC Sensitivity by R. Deborah Overath, Department of Life Sciences, Texas A&M University – Corpus Christi "Copyright held by the National Center for Case Study Teaching in Science, University at Buffalo, State University of New York, all rights reserved. Used with permission." This case study has been adapted for this lab. The purpose of this case study is to demonstrate that, sometimes, scientific discoveries are made by accident. Scientists have to be aware of what they are observing and be able to follow interesting questions with inquiry. This early research into PTC tasting has led to decades of further research. Work through the case study and then taste the PTC paper for yourself. Part I – Discovery* “Arthur,” said C.R. Noller in an irritated voice, “what the heck are you doing over there? Why did you let that awful tasting stuff get into the air? It’s so bitter that I want to vomit!” Drs. Arthur Fox and C.R. Noller were working separately in a lab at the DuPont Chemical Company’s facilities in Wilmington, Delaware. “What do you mean, C.R.?” snapped Arthur. “I don’t taste anything, and I’m right on top of this stuff.” “It’s got to be that powder you’ve got there,” retorted C.R. “I’m not working with anything bitter, and I’m too far from the door for it to be coming from outside the lab.” Arthur was transferring some phenylthiocarbamide (PTC) into a bottle. During the transfer, some of the white powder had dispersed into the air. “Look,” said Arthur as he licked his finger, picked up a few PTC crystals, and licked his finger again. “I don’t taste anything.”** “Arthur,” said C.R., “give me some of that stuff. I really don’t want to taste it, but I’ll do it just to prove you’re wrong!” Arthur Fox brought the bottle of PTC over to C.R. Noller, who picked up a few crystals. As soon as the crystals touched his tongue, C.R. exclaimed, “Yuck! Quick—get me something to rinse out my mouth! That stuff is just too bitter!” After C.R. rinsed out his mouth with some water, Arthur said, “Let’s see if we can find some other folks to taste this PTC to see if they taste anything.” For several days Arthur asked all his co-workers, friends, and acquaintances to taste his PTC powder and found that neither he, nor C.R., were unique. Regardless of gender, age, or ethnicity, about 60% of people tasted PTC as bitter, like C.R. The other 40% were, like Arthur himself, taste blind: PTC had no taste to them. Arthur also tested closely related chemicals with the same results. News of Arthur’s discovery was published in Science, the premier American science journal (Anonymous 1931). Shortly thereafter Arthur received the following letter: Dear Dr. Fox, 130 | P a g e I read the news of your discovery of variation in the ability to taste phenylthiocarbamide (PTC) and related compounds with great excitement. I am studying Mendelian markers in human populations. Unfortunately, we have few examples of such traits in humans, as you can see from my article recently published in the Eugenical News (1931b), which I have enclosed. Would you please send me some PTC? I would like to study this variation in tasting ability to see if it is inherited and, therefore, can be used as a Mendelian marker. Sincerely yours, L.H. Snyder, Ph.D. Professor of Genetics Ohio State University * The basic facts, scenarios, and players in this case are found in the literature. For example, Arthur Fox did discover variation in PTC sensitivity in the way described, his discovery was a news item in Science, and L.H. Snyder did write to Fox as indicated (see Anonymous 1931, Fox 1932, and Snyder 1931a). However, this narrative is a fictionalized account of these events. ** It is important to note that good laboratory practice and safety dictate that chemicals should not be tasted in the laboratory. 1. What is his hypothesis? References Anonymous. 1931. Science news: taste blindness. Science (Suppl.) 73: 14a. Fox, A. L. 1932. The relationship between chemical constitution and taste. Proc. Natl. Acad. Sci. USA 18: 115–120. Snyder, L. H. 1931a. Inherited taste deficiency. Science 74: 151–152. Snyder, L. H. 1931b. Linkage in man. Eugenical News 16: 117–119. Part II – Mendelian Genetics After obtaining some PTC from Arthur Fox, L.H. Snyder determined the PTC phenotype (can taste or cannot taste) for the members of 100 nuclear families. He first verified that gender was not a factor by 131 | P a g e comparing the number of male tasters and non-tasters to the number of female tasters and non-tasters. Because there was essentially no difference between sexes, Snyder grouped families by the phenotypes of the parents, disregarding the gender of each parent, and tabulated his data (Snyder, 1931a): Phenotypes of Children Can taste Cannot taste Parent phenotype combination Number of families Both parents can taste 40 90 16 One parent can taste, the other cannot 51 80 37 Neither parent can taste 9 0 17 Questions – Answer the following questions based on what you know and what your group members know. Make jot notes to use during the lab discussion 1. What kind of evidence would indicate that the ability to taste PTC is inherited? 2. Why was it important for Snyder to verify that males and females had similar proportions of tasters and non-tasters? 3. Why do couples who can taste PTC have children who cannot? 4. What is the significance of the fact that couples who cannot taste PTC ever have children who can? Reference Snyder, L. H. 1931a. Inherited taste deficiency. Science 74: 151–152. 132 | P a g e PTC Sensitivity: Linking genes and traits Phenylthiocarbamide (PTC) is an anti-thyroid drug that prevents the thyroid gland from incorporating iodine into the thyroid hormone. The ability to taste PTC is associated with the functioning of the thyroid gland. Since the early 1930s, when the ability to taste PTC was discovered, researchers in diverse areas of science, including genetics, ecology, evolution, nutrition and psychology, have all contributed to understanding the role of the gene that controls for the ability to taste PTC in our evolutionary history. In this activity you will get the opportunity to determine if you are a PTC taster or not. You will need to get a piece of paper that has been impregnated with PTC. Also note the following information: - The gene for tasting PTC is on an autosome Tasting (A) is dominant over not tasting (a) Put the PTC paper on your tongue to determine if you are a taster. If you are a taster, you will know it right away. If you are not a taster, take a look around because watching tasters taste PTC is quite amusing! Dispose of the PTC paper where indicated by your lab TA. 1. Were you able to taste the PTC in the paper? Tasted like paper Tasted bitter Tasted TERRIBLE! 2. What do you think your genotype is? Explain. Genetics Problem: Joe cannot taste PTC, but both his mother and father can taste PTC. a. What is Joe’s genotype? b. What genotype do Joe’s parents have? 133 | P a g e c. Draw the Punnett Square for the cross between Joe’s parents. Include the genotypic and phenotypic ratios. d. What is the percent chance that a child will be able to taste PTC? e. What is the percent chance that a child will not be able to taste PTC? This activity is a TA Checkpoint. Have your Punnett Square checked and initialled by a lab Teaching Assistant. 134 | P a g e Tracking two traits – Two gene cross Finger length is determined by a single gene and is long or short. Hairline is also determined by a single gene and can be straight or pointed. A pointed hairline is often referred to as a Widow’s peak. Tracking two traits together can answer the question as to whether or not some traits are always inherited together. In order for the Punnett Square to answer the question, we have to be looking at traits that are generally found on separate chromosomes. Genetics Problem Finger length: Short Fingers (A) is dominant over long fingers (a) Hairline: Widow’s peak (B) is dominant over straight hairline (b) Think about tracking these two traits together. Write in all of the combinations of gene pairs. Use the first two as examples. Genotype Description Homozygous for short fingers and Widow’s Peak Homozygous for short fingers, heterozygous for hairline Genotype AABB Gametes AB AABb AB, Ab 135 | P a g e A man and a woman that are both heterozygous for short fingers and Widow’s Peak have children. Draw the Punnett Square for this cross. Write out the genotypic and phenotypic ratios. What is the name given to this pattern? Hint: we discussed it in class. 136 | P a g e A man with long fingers and a straight hairline has children with a woman that is heterozygous for both short fingers and Widow’s Peak. Draw the Punnett Square for this cross. Write out the genotypic and phenotypic ratios. This activity is a TA Checkpoint. Have your Punnett Square checked and initialled by a lab Teaching Assistant. 137 | P a g e Blood Type – Multiple Allele Inheritance and Co-dominance Red blood cells have proteins on the outside of the plasma membrane and these proteins indicate the type of blood a person has. The cell knows what proteins to put on the outside of the plasma membrane based on the genes for blood type. For many genes there are only two alleles, or two options for the gene. In the case of the gene for blood type, there are three alleles, or three different possibilities for blood type. There are two dominant alleles and 1 recessive allele. Allele Dominant/Recessive A Dominant B Dominant o Recessive The fact that there are two dominant alleles makes for a unique outcome when the two dominant alleles are paired in the cells. Genotype Phenotype/Blood type AA A Ao A BB B Bo B oo O AB AB Genetics Problem: Mark has blood type O. His mother has blood type A. Two men provide blood samples to try to figure out which might be Mark’s father. a) What is Mark’s genotype? b) What is Mark’s mother’s genotype? 138 | P a g e c) Male A has blood type AB. Could he be Mark’s father? Explain. d) Male B has blood type B. Could he be Mark’s father? Explain. This activity is a TA Checkpoint. Have your Punnett Square checked and initialled by a lab Teaching Assistant. 139 | P a g e Sex-linked traits – Colour Blindness Sex chromosomes have genes that determine the sex of the individual. The X chromosome is larger than the Y chromosome, and also has genes that determine traits other traits, such as colour vision. Colour blindness is an X-linked, recessive trait, which means the genes are on the X chromosome. The abbreviations for the chromosomes carried on the X chromosome are written in the capital letter for the dominant allele and lowercase letter for the recessive allele, both written as superscripts to a capital letter X. XA – normal colour vision Xa – colour blind Fill in the following table, listing the possible genotypes and phenotypes for colour blindness. Remember to indicate if the person is male or female. Genotype Phenotype XA XA Female, normal vision 140 | P a g e Have someone in your group present the colour blindness chart to you. Write down what you see in a place that your partner cannot see it. Keep your answers hidden until all members of your group have been tested. Colour blind people see different things than people with normal colour vision. Fill in the following information: Your phenotype Your genotype Your father’s phenotype and genotype Your mother’s phenotype Draw the Punnett Square for your family. 141 | P a g e Genetics Problem: Jane and her mother are not colour blind, but her maternal grandfather was colour blind. What are her maternal grandfather’s and her mother’s? What are Jane’s possible genotypes? If Jane’s father is not colour blind, is there a possibility that Jane could have colour blind siblings? Draw the required Punnett squares to answer this question. This activity is a TA Checkpoint. Have your Punnett Square checked and initialled by a lab Teaching Assistant. 142 | P a g e Incomplete Dominance – snapdragons In some cases, the dominant allele is not completely dominant over the recessive allele. When this happens, the recessive trait blends with dominant trait to create an intermediate phenotype in the offspring. Genotype AA Aa aa Phenotype Dominant Intermediate Recessive Genetics Problems: In snapdragons, flower colour (red, pink, white) results from a pair of alleles where the dominant, red, allele is not completely dominant over the recessive, white allele. A plant with red flowers is crossed with a plant with white flowers. What are the genotypes of the parents? What types of gametes does each parent make? Draw the Punnett Square for this cross. 143 | P a g e What are the expected genotype and phenotype ratios for their offspring? Draw the Punnett Square for the offspring of the first cross. What are the expected genotype and phenotype ratios of this cross? Blending inheritance is the idea that the traits of the parents are blended in the offspring. How is flower colour in snapdragons an example that might support the hypothesis of blending inheritance? 144 | P a g e Human Height – Multifactorial Inheritance Some human traits are controlled by more than just the genes that are inherited from the parents. Some traits are also strongly influenced by environment factors. Human height is an example of a trait that is controlled by both the genes a person has and the environment they are in during development. In humans, a person has genes that dictate the ultimate height that person can grow to. The expression of those genes is affected by early childhood nutrition. If a young child has good nutrition while they are a toddler, they are more likely to grow to the maximum height dictated by their genes. If a young child has poor nutrition while they are a toddler, they are less likely to reach the maximum height dictated by their genes. The genes for height are inherited following the patterns of Mendelian genetics. Thinking back to the story presented at the beginning of the lab, how might multifactorial inheritance explain why Lucy is shorter than the rest of her family? What information is missing from the story that would help you figure this out? Lab assessments In lab - Karyotypes - Punnett Squares - Case study questions Homework - Study concepts using study guide 145 | P a g e Study guide Outline of topics that should be understood for the lab exam 1. Understand the genetics terms from the lab. Create a glossary of the terms. Consider using cue cards. 2. Understand how a karyotype is created and used. What kinds of questions can be answered with a karyotype? 3. Understand how a Punnett Square is made and how it can be used to predict outcomes of crosses. 4. Understand the history of the discovery of the ability to taste PTC. 5. Understand the 9:3:3:1 phenotypic ratio of a cross between heterozygotes when tracking two traits at a time. 6. Understand the multiple alleles involved in blood typing. Work through the examples to determine when blood typing can be used to determine the parents of a child. 7. Understand how sex-linked traits found on the X chromosome are inherited and expressed. Understand the example of colour vision. 8. Understand how incomplete dominance works and the example of snapdragons. 9. Relate the information on multifactorial inheritance to the story about human height at the beginning of the lab. Resources Mendelian Genetics: http://www.dnaftb.org/1/ Karyotype Activity: http://www.biology.arizona.edu/human_bio/activities/karyotyping/karyotyping.html PTC: http://www.ncbi.nlm.nih.gov/pubmed/11293722 More PTC: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456409/ Human height and childhood nutrition: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2258311/ EXTRA QUESTIONS: http://biology.clc.uc.edu/courses/bio105/geneprob.htm http://www.ksu.edu/biology/pob/genetics/intro.htm 146 | P a g e