ABCS 355 Molecular Genetics Past Paper PDF 2020-2021

ABCS 355 MOLECULAR GENETICS (2 credits) Bethel Kwansa-Bentum, PhD Senior Lecturer | Departmental Examinations Officer  Course outline Structure and function of DNA and RNA Regulation of gene transcription and expression of prokaryotes Mutations and c...

ABCS 355 MOLECULAR GENETICS (2 credits) Bethel Kwansa-Bentum, PhD Senior Lecturer | Departmental Examinations Officer  Course outline Structure and function of DNA and RNA Regulation of gene transcription and expression of prokaryotes Mutations and concomitant altered proteins Behavioural genetics, prokaryotic gene expression, gene mapping, biomedical genetics 2  Objectives 1. Discuss the path to Watson and Crick model of the DNA 2. Discuss the Watson and Crick model of the DNA 3. Explain the processes of the Central Dogma 4. Discuss the properties of the Genetic code 5. Discuss how cells regulate expression of genes 6. Differentiate between Mutations and Polymorphisms 7. Explain the roles of genes biomedicine, and in behaviour of organisms 8. Outline the importance of gene mapping 3  References 1. Griffiths, A. J. F., Wessler, S. R., Lewontin, R. C. and Carroll, B. S. (2010). Introduction to genetic analysis, 10th edition, W. H. Freeman and Company, New York. 2. Gurbachan, S. M. (2015). Essentials of Molecular Genetics. Alpha Science International Ltd., Oxford, U.K. 3. Klug, W. S., and Cummings, M. R. (2003). Concepts of genetics. Upper Saddle River, Prentice Hall, New Jersey. 4. Russell, P.J. (2000). Fundamentals of Genetics, 2nd edition. Addison Wesley Longman. 5. Snustad, D. P., Simmons, M. J., & Jenkins, J. B. (1997). Principles of Genetics. John Wiley and Sons Inc. New York. 6. Strachan, T. and Read, A. (2010). Human Molecular Genetics. 4th Edition Garland Science, U.S.A. 4  Course delivery schedule Wk Date Topic Comment 1 6th Apr. 2021 Path to the Watson and Crick Contributions of scientists to model understanding the nature of DNA 2 13th Apr. 2021 Watson and Crick model of the Distinguish between nucleoside and DNA. RNA structure nucleotide. Significance of base-pairing DNA vs. RNA 3 20th Apr 2021 The Central dogma DNA replication, Transcription, Translation 4 27th Apr 2021 The Genetic Code Properties of the genetic code Mutations and Polymorphisms Types of mutations Types of polymorphisms 5 4th May 2021 Behavioural genetics, Prokaryotic Significance of gene regulation gene expression Operon 6 11th May 2021 Gene mapping, Biomedical genetics 5 The Path to the Watson and Crick model 6  Section objectives 1. Define gene at the molecular level 2. Discuss contributions of scientists to understanding the nature of DNA 7  Gene – the unit of heredity Genes are organized in structures called chromosomes Physical location of a gene is its locus Different versions of genes are called alleles – E.g., the gene for eye colour may have a blue allele and a brown allele Genes determine virtually all characteristics of an organism Most genes come in pairs and are made of strands of genetic material called deoxyribonucleic acid (DNA) Gene is sequence of nucleotides that codes for a protein 8  Characteristics of Genetic material A molecule must possess these qualities to function as a genetic material 1. Repository of all information required by the cell 2. Capable of transferring its information to the cell on demand 3. Capable of faithful replication so that the information it contains can be passed on to the next generation 4. Stable enough so that mutations in the nucleotide sequence of the molecule are rare 9  Griffith’s Transformation Experiment (1928) First experiment on transfer of genetic information S-strain of Pneumococcus bacteria caused fatal infections when injected into mice R-strain bacteria did not cause any fatal infection ‘Heat-treated’ S-strain also caused no infection 10  Avery, Macleod, McCarty (1944) They labelled the DNA of a bacteriophage with radioactive phosphorus. DNA (not proteins) can transform the properties of genes 11  Hershey & Chase (1952) Confirmatory test that DNA is the genetic material 12  Rosalind Elsie Franklin (1952) 1952: Rosalind Franklin obtained x-ray diffraction pattern that triggered the idea that DNA was a helix 1953: Watson & Crick – elucidated the molecular model of DNA structure as a double helix 13  Summary 1869: Friedrich Miescher identified DNA 1928: Griffith performed the first experiment that suggested bacteria are capable of transferring genetic information through a process known as transformation 1944: Avery, MacLeod & McCarty – showed that DNA (not proteins) can transform the properties of genes, clarifying the chemical nature of genes 1952: Hershey and Chase experiment helped confirm that DNA is the genetic material 1952: Rosalind Franklin obtained x-ray diffraction pattern that triggered the idea that DNA was a helix 1953: Watson & Crick – elucidated the molecular model of DNA structure as a double helix 14 Watson and Crick model of the structure of DNA 15  Objectives 1. Distinguish between nucleoside and nucleotide 2. Comment on the importance of each of the three parts of nucleotide 3. Describe how chains of nucleotides are built up using sugar- phosphate linkages 4. Explain the significance of base-pairing 5. Distinguish between the structures of DNA and RNA 6. Discuss what account for the differences between – species – individuals of the same species – cells of the same individual – normal cells and cancer cells 16  Nucleotide The double helix model of DNA (deoxyribonucleic acid) consists of two intertwined antiparallel strands These strands are made up of nucleotides, which themselves consist of three component parts: Nucleotide – nitrogenous base – deoxyribose sugar – phosphate group 17 Nucleoside  The 5 Nitrogenous Bases 5 Nitrogenous bases, divided into two groups: – Purines (Guanine and Adenine) have two joined heterocyclic rings – Pyrimidines (Cytosine, Thymine and Uracil) have a single heterocyclic ring 18  The 4 Nitrogenous Bases in DNA 4 of these Nitrogenous bases occur in DNA – Adenine (A), Guanine (G), Cytosine (C), Thymine (T) Successive sugar and phosphate residues are linked by phosphodiester bonds, forming the DNA backbone – Phosphodiester bonds give stability to nucleotides The bases allow the two strands of DNA to hold together by hydrogen bonds – Hydrogen bonds also adds to the stability Phosphate group charges present in each nucleotide makes it negatively charged and therefore highly soluble in water 19 The Double Helix 20  The two strands are complementary Adenine always forms 2 hydrogen bonds with Thymine Guanine always forms 3 hydrogen bonds with Cytosine This pairing makes it possible to work out the sequence of bases on one strand using the opposite strand This property allows the DNA to replicate itself 21  The two strands are antiparallel The two DNA strands are antiparallel because they always associate (anneal) in such a way that the 5’-3’ direction of one DNA strand is the opposite to that of its partner 22  Structure of DNA DNA is composed of two polynucleotide chains that coil around each other to form a double helix Carries genetic instructions for the growth, development, functioning, and reproduction of all known organisms and many viruses Each turn of helix is made up of 10.4 nucleotide pairs 23  Erwin Chargaff’s rule (1950) Number of Purine base (A+G) is equal to the number of Pyrimidine bases (C+T) Ratio of Adenine to Thymine is close to unity. i.e. A/T =1 Ratio of Guanine to Cytosine is close to unity. i.e. G/C =1 A+T is not necessarily equal to G+C, a pattern found in both strands of the DNA 24  Erwin Chargaff’s rule (1950) A+T/G+C is not fixed and varies in DNA of several species to a fixed number If A+T/G+C is more than unity = DNA is of AT type If A+T/G+C is less than unity = DNA is of GC type Bacteria have both kind of DNA’s (AT type and GC type) Higher organisms always have greater than 1 – Animals; 1.2 to 2.3 (Humans, 1.4) – Plants; 1.1 to 1.7 25  Summary 1. DNA strands are made up of nucleotides, consisting of nitrogenous base, deoxyribose sugar, and phosphate group 2. Successive sugar and phosphate residues are linked by phosphodiester bonds, forming the backbone of the DNA molecule 3. The bases allow the two strands of DNA to hold together by hydrogen bonds 4. Adenine always pairs with Thymine 5. Guanine always pairs with Cytosine 6. The two DNA strands are complementary 7. The two DNA strands are antiparallel 26 Structure of RNA 27  Three main types of RNA Transcript copy of a gene Primary component of Clover-leaf shaped sequence used to encode a polypeptide ribosomes that carries an amino acid 28  The 4 nitrogenous bases of RNA RNA nucleotides, like those from DNA, have three parts: a ribose sugar, a phosphate group and a base Slightly different group of 4 bases occur in RNA – Adenine (A), Guanine (G), Cytosine (C), Uracil (U) Uracil is a pyrimidine that is structurally similar to the thymine (pyrimidine) found in DNA Like thymine, uracil can base-pair with adenine 29 DNA vs. RNA 30  DNA vs. RNA Which is the genetic material? – DNA/ RNA / Protein 1. Why is DNA the genetic material and not RNA? 2. What is the significance of Uracil replacing Thymine (in RNA) in the central dogma of life 31  1. Why DNA the genetic material and not RNA? Deoxyribose sugar, with one less oxygen-containing hydroxyl group is a more stable molecule than Ribose sugar Useful for a molecule that has the task of keeping genetic information safe 32  2. Significance of Uracil replacing Thymine in RNA Uracil is energetically less expensive to produce than thymine, which may account for its use in RNA In DNA, however, uracil is readily produced by chemical degradation of cytosine, so having thymine as the normal base makes detection and repair of such incipient mutations more efficient Thymine has a greater resistance to photochemical mutation, making the genetic message more stable. Thus, thymine is more protected than uracil 33  Some more biological questions 3. If all DNA is made of the same material (i.e. A, G, C, T), what then accounts for the following? a. The differences between species? b. The differences between individuals of the same species? c. The differences between cells of the same individual? d. The differences between normal cells and cancer cells? 34 35  Differences between species Percentages of each nucleotides in a DNA molecule do not account for the differences in species Organisms with vastly different amounts of DNA may still have the same percentage of each of the nucleotides – An organism with 10,000 bp in its DNA may have 1,000 Adenines – Another organism with 1,000,000 bp may have 100,000 Adenines – But both have DNA composed of 10% Adenines 36  Differences between species Differences in base sequence Total amount of DNA present in the cells 37 Differences between individuals of the same species For all members of the same species, the total amount of DNA would be about the same Differences in base sequence Nature of satellite DNA 38  Differences between cells of the same individual Differences in gene expression patterns Different cell types have different genes and sets of genes in an active state 39  Differences between normal and cancerous cells Almost universal change in chromosomal complement of cancer cells Cancer cells are not true diploid – They are aneuploid (change in chromosome number by loss or duplication of chromosomal segments) 40 Central Dogma of Biology 41  Objectives 1. State the requirements for replication of double stranded DNA 2. Differentiate between synthesis of the leading strand and lagging strand 3. State the functions of key enzymes in DNA replication 4. Discuss the steps involved in replicating DNA 5. Describe the process of transcription leading to the formation of messenger RNA complementary to the DNA strand 6. Explain the term translation and describe the role of ribosomes and transfer RNA in carrying out this process 7. Differentiate between transcription and translation in prokaryotes and eukaryotes 42  Central Dogma Explains the flow of genetic information within biological system Involves DNA replication to DNA, DNA transcription to RNA and RNA translation to proteins All 3 stages (Replication/ Transcription/ Translation) have 3 steps (Initiation/ Elongation/ Termination) each 43 Replication 44  DNA replication Replication in DNA is semi-conservative Double-stranded DNA molecule is copied to produce two identical DNA molecules Once the DNA in a cell is replicated, the cell can divide into two cells, each of which has an identical copy of the original DNA 45  Initiation DNA synthesis is initiated at specific points (origins) within the DNA strand (and there are multiple origin sites) When replication of DNA begins, these sites are referred to as Replication forks Within the replication complex is the enzyme DNA Helicase, which unwinds the double helix exposing each of the two strands 46  Initiation Single Stranded Binding Proteins stabilizes the newly single stranded regions DNA Gyrase ensures the double stranded areas outside of the replication fork do not supercoil Eukaryotes have Type II Topoisomerase instead of DNA Gyrase for the same purpose 47  Initiation DNA Polymerase, the ultimate enzyme responsible for the creation and expansion of the new strands of DNA – Catalyze the addition of new nucleotide to the growing daughter strand – DNA polymerase cannot begin to add nucleotides without a primer DNA Primase adds short sequences of RNA (primers) to the template strands 48 Elongation 49  Elongation DNA synthesis occurs on the 3’ – 5’ oriented parent strand. Thus, the new strand is formed in a 5’ – 3’ direction. This newly formed strand is referred to as the Leading Strand. Along this strand, DNA Primase only needs to synthesize an RNA primer once, at the beginning, to initiate DNA Polymerase. This is because DNA Polymerase is able to extend the new DNA strand by reading the template 3′ – 5′, synthesizing in a 5′ – 3′ direction 50  Elongation However, the other template strand (lagging strand) is antiparallel, and is therefore read in a 5’ – 3’ direction Continuous DNA synthesis, as in the leading strand, would need to be in the 3′ – 5′ direction, which is impossible as bases cannot be added to the 5′ end Instead, as the helix unwinds, RNA primers are added to the newly exposed bases on the lagging strand and DNA synthesis occurs in fragments, but still in the 5′ – 3′ direction as before These fragments are known as Okazaki fragments 51  Termination The process of expanding the new DNA strands continues until there is either of two things happen 1. No more DNA template left to replicate (i.e. at the end of the chromosome) 2. Two replication forks meet and subsequently terminate. 52  Termination Once DNA synthesis has finished, newly synthesized strands are bound and stabilized With regards to the lagging strand, two enzymes are needed to achieve this; 1. Ribonuclease H (RNase H) removes the RNA primer that is at the beginning of each Okazaki fragment 2. DNA Ligase joins fragments together to create one complete strand 53 Transcription 54  Transcription Process by which information in a strand of DNA is copied into a new molecule of messenger RNA (mRNA) The sequence of DNA that is transcribed into RNA is called a Gene DNA safely and stably stores genetic material in the nuclei of cells as a reference, or template Although the mRNA contains the same information, it is not an identical copy of the DNA segment, because its sequence is complementary to the DNA template 55 Initiation 56 Elongation / Non-coding strand Codons Anti-codons 57  Elongation One strand of DNA, the template strand, acts as a template for RNA polymerase As the polymerase ‘reads’ this template one base at a time, the polymerase builds an RNA molecule out of complementary nucleotides, making a chain that grows from 5’ – 3’ The RNA transcript carries the same information as the non-template (coding) strand of DNA, but it contains the base uracil (U) instead of thymine (T) 58  Elongation DNA is double stranded, but only one strand serves as a template for transcription at any given time This template strand is called the non-coding strand The non-template strand is referred to as the coding strand because its sequence will be the same as that of the new RNA molecule 59  Termination Terminator sequences signal that RNA transcript is complete Once transcribed, they cause the transcript to be released from the RNA polymerase 60 Eukaryotic RNA modifications 61  Eukaryotic RNA modifications The ends of pre-mRNAs are modified by addition of a 5' cap (at the beginning) and 3' poly-A tail (at the end) – End modifications increase the stability of the mRNA as it prepares to leave the nucleus to the cytoplasm Many eukaryotic pre-mRNAs undergo splicing, where parts of the pre-mRNA (called introns) are chopped out, and the remaining pieces (called exons) are stuck back together – Splicing gives the mRNA its correct sequence. Thus, if introns are not removed, they will be translated along with the exons, producing a ‘gibberish’ polypeptide 62 Translation 63  Translation Decoding mRNA and using its information to build a polypeptide/ protein (amino acids chain) – Some large proteins are made up of several polypeptide chains Codons of mRNA are read from 5’ – 3’ end by molecules called tRNAs Each tRNA has an Anticodon – a set of three nucleotides that binds to a matching mRNA codon through base pairing The other end of the tRNA carries the amino acid that is specified by the codon 64  Codons of amino acids tRNAs bind to mRNAs inside of a protein-and-RNA structure called the Ribosome As tRNAs enter slots in the ribosome and bind to codons, their amino acids are linked to the growing polypeptide chain in a chemical reaction Results in a polypeptide whose amino acid sequence mirrors the sequence of codons in the mRNA 65  Initiation The tRNA carrying methionine attaches to the small ribosomal subunit Together, they bind to the 5’ end of the mRNA by recognizing the 5’ cap (added during processing in the nucleus) Then, they ‘walk’ along the mRNA in the 3’ direction, stopping when they reach the start codon, often (but not always) the first AUG 66 Eukaryotic translation initiation 1. Ribosome (which comes in two pieces, large and small) 2. mRNA with instructions for the protein that is needed to be built 3. tRNA carrying the first amino acid in the protein, which is almost always methionine (Met) Together, they form the Initiation Complex – the molecular setup needed to start making a new protein 67  Bacterial translation initiation The small ribosomal subunit attaches directly to certain sequences in the mRNA – Shine-Dalgarno sequences These come just before start codons and ‘point them out’ to the ribosome 68  Elongation A=Aminoacyl site, P=Peptidyl site, E=Exit site 69  Elongation The first methionine-carrying tRNA starts out in the middle slot of the ribosome, called the P site Next to it, a fresh codon is exposed in another slot, called the A site The A site is the ‘landing site’ for the next tRNA, one whose anticodon is a perfect (complementary) match for the exposed codon 70  Elongation Once the matching tRNA lands in the A site, peptide bond is formed between methionine (in P site) and the amino acid on the tRNA in the A site This step transfers the methionine from the first tRNA onto the amino acid of the second tRNA in the A site The methionine forms the N-terminus of the polypeptide, and the other amino acid is the C-terminus 71  Elongation The mRNA moves a codon further into the ribosome, pushing the methionine to the E site The second tRNA with the polypeptide now moves to the P site, making the A site open to receive the next complementary tRNA (with amino acid) that matches the codon in the A site This continues till the end of the growing polypeptide chain 72  Termination Termination happens when a stop codon in the mRNA (UAA, UAG, or UGA) enters the A site Stop codons are recognized by proteins called release factors, which fit neatly into the P site (though they aren't tRNAs) Release factors mess with the enzyme that normally forms peptide bonds, leading to the addition of water molecule to the last amino acid of the chain This reaction separates the chain from the tRNA, and the newly made protein is released 73  Processing Polypeptides need some ‘edits’. During and after translation, amino acids may be chemically altered or removed The new polypeptide will also fold into a distinct 3D structure and may join with other polypeptides to make a multi-part protein Many proteins are good at folding on their own, but some need helpers (chaperones) to keep them from sticking together incorrectly during the complex process of folding Some proteins also contain special amino acid sequences that direct them to certain parts of the cell. These sequences, often found close to the N-terminus or C-terminus, can be thought of as the protein’s “train ticket” to its final destination 74  Summary Transcription occurs in the nucleus, copying coded instructions from DNA to produce mRNA that pass to the cytoplasm Translation occurs inside ribosomes where protein molecules are assembled by interpreting the coded message Translation uses tRNA molecules and ribosomes (rRNA) to join amino acids into a polypeptide chain according to the mRNA sequence (as read in codons) 75 The Genetic Code 76  Objectives 1. Describe how genetic instructions stored in DNA are decoded to produce amino acid 2. Explain how 4 nucleotides lead to the production of 64 codons 3. Discuss the properties of the genetic code 77  Genetic code Dictionary of genetic code employs the letters in RNA (U, C, A, G) Three-letter combinations (triplet codon) of nucleotides called codons Each triplet codon corresponds to a specific amino acid (20 amino acids exist) or stop signal 43 (i.e. 64) codons dictionary possible combinations exist – the Genetic Code 78  Genetic code 2nd base 3rd base 1st base 79  Genetic code More than one codon can signal a particular amino acid to be incorporated into a protein The special function codon, AUG serves two purposes 1. Initiates codon signaling for the start of synthesis of a peptide 2. Incorporates methionine into the growing chain of a peptide 80  Genetic code Other special-purpose codons are UAA (Ochre), UAG (Amber), UGA (Umber), all of which signal STOP. When the ribosomal synthesis site encounters one of these stop codons, the peptide chain is released and assumes its secondary and tertiary structures Since UAA (Ochre), UAG (Amber) and UGA (Umber) do not specify any amino acid they are also called Nonsense codons 81 Properties of the Genetic Code 82  1. Code is Universal All known living organisms use the same genetic code – prokaryotes and eukaryotes 2. Code is Unambiguous Each codon codes for just one amino acid (or start or stop) A given codon always codes for a particular amino acid, wherever it is present 83  3. Code is Redundant Most amino acids are encoded by more than one codon. The occurrence of more than one codon for a single amino acid is also referred to as degenerate 4. Code is a Triplet The coding units or codons for amino acids comprise three letter words, 4 x 4 x 4 = 43 = 64 64 codons specify 20 proteinous amino acids 84  5. Code is Non-overlapping In a non-overlapping code, the same letter (i.e., base) is not used in the formation of more than one codon. 6. Code is Comma-less No punctuation present in between two codons. Thus, code is continuous and comma-less and no letter is wasted between two words or codons 85  7. Code is Co-linear The gene and the polypeptide it codes for are said to be co-linear – DNA is a linear polynucleotide chain – Protein is a linear polypeptide chain The sequence of amino acids in a polypeptide chain corresponds to the sequence of nucleotide bases in the gene (DNA) that codes for it Change in specific codon in DNA produces a change of amino acid in the corresponding position in the polypeptide 86  8. Code shows Gene-Polypeptide parity One gene one polypeptide rule – a specific gene transcribes a specific mRNA that produces a specific polypeptide Thus, a cell can have only as many types of polypeptides as it has types of genes Some proteins have a number of polypeptide chains and thus need multiple genes A mutated gene may synthesize a defective polypeptide, hence affecting protein function 87  Summary The genetic code consists of the sequence of bases in DNA or RNA Groups of three bases form codons, and each codon stands for one amino acid (or start or stop) The codons are read in sequence following the start codon until a stop codon is reached The genetic code is universal, unambiguous, and redundant 88 Mutations and Polymorphisms 89  Objectives 1. Distinguish between deletion, inversion, translocation and duplication as forms of chromosome mutation 2. Differentiate between mutation and polymorphism 3. Explain how mutations come about 90  Genetic variation Genetic variation refers to genetic difference between individuals within or between different populations This variation is what renders each individual unique in its phenotypic characteristics Genetic variation occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes 91  Mutations Any change in a DNA sequence away from normal Thus, there is a normal allele that is prevalent in the population and that the mutation changes this to a rare and abnormal variant 92  Types of mutations In terms of DNA structure, mutations can be categorized as: 1. Point mutation 2. Insertion 3. Deletion 4. Inversion 5. Translocation 6. Duplication/ Amplification 93  Point mutation Caused by a change in a single nucleotide, when a DNA nucleotide is replaced by a different nucleotide 94 Point mutation 95  Insertion Insertion of one or more nucleotides in the normal DNA sequence This can affect the splicing or the reading frame, leading to an incorrect reading of all the downstream nucleotide triplets Consequently, their translation to a significantly different and/or truncated amino acid sequence 96  Deletion Removal of one or more nucleotides from the normal DNA sequence Can lead to minor or major protein defects with implications for the entire downstream amino acid sequence of the mutant protein 97  Inversion Reversal of DNA segment orientation with variable implications for the protein product 98  Translocation Addition of genes from another chromosome Regions from non-homologous chromosomes are interchanged 99  Duplication/ Amplification Amplifications leading to multiple copies of chromosomal regions Thereby increasing the number of copies of the genes located within them and increased levels of the corresponding proteins 100  Causes of mutation Common causes Description Spontaneous Aberrant recombination Abnormal crossing over may cause deletions, duplication, translocations, inversions Aberrant segregation Abnormal chromosomal segregation may cause aneuploidy or polyploidy Errors in DNA replication A mistake by DNA polymerase may lead to point mutation Toxic metabolic products Products of normal metabolic processes may be chemically reactive agents that can alter the DNA structure 101  Causes of mutation Common causes Description Spontaneous Transposable elements These can insert themselves into the sequence of a gene Depurination Linkage between purines (i.e. adenine and guanine) and deoxyribose can spontaneously break. If not repaired may lead to mutation Deamination Cytosine and 5-methyl cytosine can spontaneously deaminate to create uracil or thymine Tautomeric shift Spontaneous changes in base structure can cause mutation if they occur immediately prior to DNA replication 102  Causes of mutation Common causes Description Induced Physical agents High energy radiation such as X-ray, B-ray, Gamma ray, Ultraviolet ray may damage DNA by causing the formation of Thymine dimers Chemical agents May cause changes in the DNA structure by competing with natural bases Ethidium bromide insert in between paired bases Base analogues (5-bromouracil, 2-aminopurine, nitrous acid, hydroxylamine ) competes with natural bases Nitrosamines in Tobacco, Benzenes and mustard gas 103  Polymorphisms Poly = many; Morphism = form Many types of phenotypic expressions (in the population) – E.g., ABO blood grouping Dimorphism (E.g., Sexual dimorphism) Monomorphism (E.g., Birds are highly monomorphic) Polymorphism is caused by mutation, and it is heritable in nature Together with other genetic and environmental factors, polymorphism affect – disease predisposition – disease progression – response to treatments 104  Single Nucleotide Polymorphisms (SNPs) Single base changes that occur (on average) about every 1000 bases in the genome Most SNPs are neutral, but some affect the phenotype of the individual carrying them 105