Professor Too Bright

O O T R O S PROFES BRIGHT

2 M LE B O R P L B P 1 0 0 1 C S MD TUTOR: DR S. CHASE

LIST OF OBJECTIVES 1. 2. 3. 4. 5. 6. 7.

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS. BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS COMPARE THE AMINO ACIDS NEEDS OF HUMANS AND SOME DOMESTIC ANIMALS EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS BRIEFLY DISCUSS HOW THE PROPERTIES OF AMINO ACIDS AFFECT THE PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS EXPLAIN THE BASIS OF SICKLE CELL ANAEMIA DESCRIBE THE DIFFERENT TYPES OF POINT MUTATIONS AND THEIR POSSIBLE EFFECTS ON PROTEIN STRUCTURE AND FUNCTION DISCUSS THE ROLE OF EPIDEMIOLOGY IN UNDERSTANDING CAUSES OF ILL HEALTH AND THE SPREAD OF DISEASE

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS

• FIRSTLY, HISTOLOGY IS A GREEK WORD WHICH TRANSLATES TO HISTOS "TISSUE", AND LOGIA “SCIENCE”. HENCE HISTOLOGY IS MICROSCOPIC ANATOMY.

• IN COMPARING THE HISTOLOGY AMONG HUMANS, RATS AND CHICKEN BLOOD CELLS WE MUST FIRST

TAKE INTO ACCOUNT THAT BOTH RATS AND HUMANS ARE MAMMALS, WHILE, CHICKENS ARE NOT. THIS THEREFORE SIGNIFIES THAT THERE WILL BE SOME SIGNIFICANT DIFFERENCES BETWEEN THESE ANIMALS HISTOLOGY.

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS

• HUMAN ERYTHROCYTES UNDERGO THEIR MATURATION IN THE BONE MARROW, WHICH CONSISTS OF

SEVERAL STAGES IN WHICH ALL NUCLEIC MATERIAL IS REMOVED FROM THE CELLS, AND THE PROTEIN HAEMOGLOBIN IS MASS SYNTHESIZED WITHIN THE CELLS. EVENTUALLY AROUND 90% OF THE DRY WEIGHT OF THE CELL IS MADE UP OF THIS PROTEIN. THE NUCLEUS IS LOST FROM THE CELL. THE RED BLOOD CELLS CAN THEN ENTER THE CIRCULATION. THE CELL ASSUMES A BI-CONCAVE SHAPE : WHICH IS CHARACTERISTIC OF HUMAN RED BLOOD CELLS.

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS Human RBC viewed under light microscope

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS • HUMAN ERYTHROCYTES ARE BICONCAVE DISC SHAPED WITH OUT A NUCLEUS. • IT IS A GENETIC ADAPTATION; WITHOUT NUCLEUS MORE SPACE FOR HAEMOGLOBIN IS FREE. AND

HAEMOGLOBIN IS THE CARRIER OF OXYGEN. HENCE, THIS CAN SIMPLY BE EXPLAINED BY THE NEED FOR MAXIMUM SURFACE AREA FOR MAXIMUM OXYGEN CARRYING CAPACITY.

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS

• THE RBC OF CHICKENS HOWEVER, IS LARGE, CONVEX, WITH AN OVAL NUCLEUS. THEY ALSO CONTAIN ALL

THREE FILAMENT SYSTEMS THAT ARE FOUND IN THE MAJORITY OF SOMATIC CELLS (INTERMEDIATE FILAMENTS, MICROTUBULES AND ACTIN FILAMENTS) WHEREAS HUMAN RBC ONLY CONTAIN ONE FILAMENT SYSTEM (ACTIN FILAMENTS). OTHER THAN THAT, THE HAEMOGLOBIN OF CHICKEN BLOOD CELLS IS LARGELY SIMILAR TO HUMAN RED BLOOD CELLS, ONLY DIFFERING BY TWO AMINO ACIDS IN THE PRIMARY SEQUENCE.

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS •Chicken erythrocytes are elongated and nucleated:

DISCUSS THE HISTOLOGY OF HUMAN RED BLOOD CELLS AND BRIEFLY COMPARE THE HISTOLOGY OF HUMAN CHICKEN AND RAT RED BLOOD CELLS Chicken RBC under light microscope

COMPARE THE AMINO ACIDS NEEDS OF HUMANS AND SOME DOMESTIC ANIMALS • AMINO ACIDS ARE A GROUP OF COMPOUNDS WITH AT LEAST 1 AMINO GROUP, A CARBOXYL GROUP AND A DISTINCTIVE ‘R’ GROUP. • EIGHT AMINO ACIDS ARE ESSENTIAL FOR HUMANS, AS THE BODY CANNOT PRODUCE THEM BY THEMSELVES, AND THEY HAVE TO BE SUPPLIED EXTERNALLY. THESE ARE: ISOLEUCINE, LEUCINE, LYSINE, METHIONINE, PHENYLALANINE, THREONINE, TRYPTOPHAN AND VALINE.

• ARGININE AND HISTIDINE FORM THE GROUP OF SO-CALLED SEMI-ESSENTIAL AMINO ACIDS. THEY HAVE TO BE CONSUMED IN THE DIET UNDER CERTAIN CIRCUMSTANCES.

• THE TEN NON-ESSENTIAL AMINO ACIDS ARE ABLE TO BE PRODUCED IN THE BODY. THE FOLLOWING AMINO ACIDS FALL INTO THIS CATEGORY: ALANINE, ASPARAGINE, ASPARTIC ACID, CYSTEINE, GLUTAMINE, GLUTAMIC ACID, GLYCINE, PROLINE, SERINE AND TYROSINE.

EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS • PROTEINS ARE POLYMERS OF AMINO ACIDS AND ARE ALSO KNOW AS POLYPEPTIDES. THE AMINO ACIDS ARE CONNECTED BY A PEPTIDE BOND.

• THE UNIQUE LINEAR SEQUENCE OF A POLYPEPTIDE IS THE KNOWN AS THE PRIMARY STRUCTURE OF A PROTEIN.

EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS After synthesis, Polypeptide chains are folded or pleated into different shapes. These different shapes are known as the secondary structure of the protein. Two common examples of these secondary structures are Alpha Helices and Beta Pleated Sheets. Alpha Helices The R groups of the amino acids all extend to the outside. The helices make a complete turn every 3.6 amino acids (residues). The helices are right handed; it twits in a clockwise direction. Beta Conformation Consists of pairs of chains lying side-by-side, stabilized by hydrogen bods between the carbonyl oxygen atom on one chain and the -NH group on the adjacent chain. The chains are often “anti –parallel”. Secondary structure is held together by hydrogen bonds overall giving the shape great stability.

EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS

EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS • THE THREE-DIMENSIONAL STRUCTURE OF THE ENTIRE POLYPEPTIDE CHAIN IS THE TERTIARY STRUCTURE OF A PROTEIN.

• THE TERTIARY STRUCTURE OF A PROTEIN IS HELD TOGETHER BY FOUR DIFFERENT TYPES OF BONDS AND INTERACTIONS

• DISULPHIDE BONDS, IONIC BONDS, HYDROGEN BONDS, HYDROPHOBIC AND HYDROPHILIC INTERACTIONS.

EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS

EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS • SOME PROTEINS ARE MADE UP OF MULTIPLE POLYPEPTIDE CHAINS SOMETIMES WITH AN INORGANIC

COMPONENT CALLED A PROSTHETIC GROUP (FOR EXAMPLE, A HAEM GROUP IN HEMOGLOBIN). EACH POLYPEPTIDE INCLUDING THE PROSTHETIC GROUP IS REFERRED TO AS A SUBUNIT OF THE PROTEIN. THE SAME FORCES AND BONDS THAT CREATE TERTIARY STRUCTURES ALSO HOLD THESE STRUCTURES TOGETHER IN A STABLE COMPLEX KNOW AS THE QUATERNARY STRUCTURE OF THE PROTEINS.

• THESE PROTEINS THAT FORM QUATERNARY STRUCTURES ARE ONLY ABLE TO FUNCTION IF ALL SUBUNITS ARE PRESENT (THE POLYPEPTIDE CHAIN AND PROSTHETIC GROUP).

EXPLAIN WHAT IS MEANT BY THE TERMS PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS

BRIEFLY DISCUSS HOW THE PROPERTIES OF AMINO ACIDS AFFECT THE PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS

• THE PROPERTIES OF THE SIDE CHAINS/R-GROUPS OF THE TWENTY AMINO ACIDS WHICH ARE PRESENT IN NEWLY SYNTHESIZED PROTEINS CAN BE CLASSIFIED AS FOLLOWS:

• POLAR / HYDROPHILIC R GROUPS- GLYCINE, SERINE, THREONINE, CYSTEINE, TYROSINE, ASPARAGINE AND GLUTAMINE • NON-POLAR R GROUPS- ALANINE, VALINE, LEUCINE, ISOLEUCINE, PROLINE, PHENYLALANINE, TRYPTOPHAN AND METHIONINE • BASIC AMINO ACIDS- LYSINE, ARGININE AND HISTIDINE • ACIDIC AMINO ACIDS- ASPARTIV ACID AND GLUTAMIC ACID •  • THE SEQUENCING OF THE 20 AMINO ACIDS LISTED ABOVE IS IMPORTANT, SINCE THEY DETERMINE THE TYPE OF INTERACTION SEEN AS

PROTEINS FOLD. THESE INTERACTIONS WOULD DETERMINE WHETHER THE PROTEIN IS PRIMARY, SECONDARY, TERTIARY OR QUATERNARY.

BRIEFLY DISCUSS HOW THE PROPERTIES OF AMINO ACIDS AFFECT THE PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS

• IN THE PRIMARY STRUCTURE, AMINO ACIDS, AS THEIR NAME INDICATES, CONTAIN BOTH A BASIC AMINO GROUP AND AN ACIDIC CARBOXYL GROUP. THIS DI FUNCTIONALITY ALLOWS THE INDIVIDUAL AMINO ACIDS TO JOIN TOGETHER IN LONG CHAINS BY FORMING PEPTIDE BONDS: AMIDE BONDS BETWEEN THE -NH2 OF ONE AMINO ACID AND THE -COOH OF ANOTHER.

•

TWO MAIN TYPES OF SECONDARY STRUCTURE ARE THE ALPHA HELIX AND THE BETA STRAND . WITH THE ALPHA HELIX WHAT IS MOST IMPORTANT IS THAT THE N-H GROUP OF AN AMINO ACID FORMS A HYDROGEN BOND WITH THE C=O GROUP OF THE AMINO ACID FOUR RESIDUES EARLIER; THIS REPEATED HYDROGEN BONDING IS THE MOST PROMINENT CHARACTERISTIC OF AN Α-HELIX. DIFFERENT AMINO-ACID SEQUENCES HAVE DIFFERENT PROPENSITIES FOR FORMING Α-HELICAL STRUCTURE. METHIONINE, ALANINE, LEUCINE, UNCHARGED GLUTAMATE, AND LYSINE ALL HAVE ESPECIALLY HIGH HELIX-FORMING PROPENSITIES, WHEREAS PROLINE AND GLYCINE HAVE POOR HELIX-FORMING PROPENSITIES. 

•

WITH THE BETA STRAND ,IT IS A STRETCH OF POLYPEPTIDE CHAIN TYPICALLY 3 TO 10 AMINO ACIDS LONG WITH BACKBONE IN AN ALMOST FULLY EXTENDED CONFORMATION. TWO ANTIPARALLEL STRANDS ARE LINKED BY A SHORT LOOP OF TWO TO FIVE RESIDUES, OF WHICH ONE IS FREQUENTLY A GLYCINE OR A PROLINE, BOTH OF WHICH CAN ASSUME THE UNUSUAL DIHEDRAL-ANGLE CONFORMATIONS REQUIRED FOR A TIGHT TURN. HOWEVER, INDIVIDUAL STRANDS CAN ALSO BE LINKED IN MORE ELABORATE WAYS WITH LONG LOOPS THAT MAY CONTAIN ALPHA HELICES OR EVEN ENTIRE PROTEIN DOMAINS

•

IN THE TERTIARY STRUCTURE THE THREE-DIMENSIONAL SHAPE OF A PROTEIN MAY SEEM IRREGULAR AND RANDOM.

BRIEFLY DISCUSS HOW THE PROPERTIES OF AMINO ACIDS AFFECT THE PRIMARY SECONDARY TERTIARY AND QUATERNARY STRUCTURE OF PROTEINS

• PHENYLALANINE OR ISOLEUCINE TEND TO BE BURIED ON THE INTERIOR OF THE PROTEIN MOLECULE THEREBY

SHIELDING THEM FROM THE AQUEOUS MEDIUM. THE ALKYL GROUPS OF ALANINE, VALINE, LEUCINE AND ISOLEUCINE OFTEN FORM HYDROPHOBIC INTERACTIONS BETWEEN ONE-ANOTHER, WHILE AROMATIC GROUPS SUCH AS THOSE OF PHENYLALANINE AND TYROSINE OFTEN STACK TOGETHER. ACIDIC OR BASIC AMINO ACID SIDE-CHAINS WILL GENERALLY BE EXPOSED ON THE SURFACE OF THE PROTEIN AS THEY ARE HYDROPHILIC.

• THE FORMATION OF DISULPHIDE BRIDGES BY OXIDATION OF THE SULFHYDRYL GROUPS ON CYSTEINE IS AN

IMPORTANT ASPECT OF THE STABILIZATION OF PROTEIN TERTIARY STRUCTURE, ALLOWING DIFFERENT PARTS OF THE PROTEIN CHAIN TO BE HELD TOGETHER COVALENTLY. ADDITIONALLY, HYDROGEN BONDS MAY FORM BETWEEN DIFFERENT SIDE-CHAIN GROUPS. AS WITH  DISULPHIDE, THESE HYDROGEN BONDS CAN BRING TOGETHER TWO PARTS OF A CHAIN THAT ARE SOME DISTANCE AWAY IN TERMS OF SEQUENCE.  SALT BRIDGES, IONIC INTERACTIONS BETWEEN POSITIVELY AND NEGATIVELY CHARGED SITES ON AMINO ACID SIDE CHAINS, ALSO HELP TO STABILIZE THE TERTIARY STRUCTURE OF A PROTEIN.

•

LASTLY IN THE QUATERNARY STRUCTURE THE FINAL SHAPE OF THE PROTEIN COMPLEX IS ONCE AGAIN STABILIZED BY VARIOUS INTERACTIONS, INCLUDING HYDROGEN-BONDING, DISULFIDE-BRIDGES AND SALT BRIDGES.

EXPLAIN THE BASIS OF SICKLE CELL ANAEMIA • THIS DISEASE IS DUE TO A POINT MUTATION ON CHROMOSOME 11. THE 6

AMINO ACID ON THE BETA CHAIN IN NORMAL HAEMOGLOBIN IS GLUTAMIC ACID WHICH IS HYDROPHILIC. IT IS CODED FOR BY CTC ON THE NORMAL DNA. DUE TO A BASE SUBSTITUTION THAT OCCURS IN THE SECOND POSITION OF THE TRIPLET, IT CHANGES TO CAC ON THE MUTANT DNA AND GUG ON THE MUTANT RNA. THIS CODES FOR THE AMINO ACID VALINE WHICH IS HYDROPHOBIC. THIS WILL RESULT IN THE HAEMOGLOBIN CRYSTALLISING INTO ROD LIKE FIBRES AS IT IS LESS SOLUBLE THAN NORMAL HAEMOGLOBIN FORMING SICKLE CELL HAEMOGLOBIN. TH

EXPLAIN THE BASIS OF SICKLE CELL ANAEMIA • EFFECT • SICKLED SHAPE OF HAEMOGLOBIN CAUSES THE TRANSPORT OF LESS OXYGEN SO THE PERSON IS SHORT OF BREATH AND EXPERIENCES FATIGUE.

• THE ABNORMAL CELLS CLUMPS TOGETHER AND CAUSES THE ABNORMAL FLOW OF BLOOD. • ISSUE • HOW IS POINT MUTATION RELATED TO SICKLE CELL ANAEMIA? • A POINT MUTATION AFFECTS A SINGLE BASE (EITHER FIRST, SECOND OR THIRD POSITION) ON THE DNA. THIS EFFECT

CAN AFFECT THE FOLDING OF THE POLYPEPTIDE CHAIN, ITS SHAPE AND PROPERTIES. THERE ARE DIFFERENT TYPES OF POINT MUTATIONS AND A BASE SUBSTITUTION WHICH OCCURS IN SICKLE CELL ANAEMIA IS ONE OF THEM.

• REFERENCE : MRS.CAROLYN BALLY-GOSINE ( BIOLOGY CLASSES)

DESCRIBE THE DIFFERENT TYPES OF POINT MUTATIONS AND THEIR POSSIBLE EFFECTS ON PROTEIN STRUCTURE AND FUNCTION • A POINT MUTATION IS AN ALTERATION IN THE SEQUENCE OF DNA (DEOXYRIBONUCLEIC ACID) RESULTING FROM A SINGLE

NUCLEOTIDE BASE CHANGE (SUBSTITUTION), INSERTION OR DELETION, USUALLY OCCURRING DURING DNA REPLICATION.

• THESE MUTATIONS CAN BE SPONTANEOUS OR INDUCED BY MUTAGENS, WHICH ARE PHYSICAL OR CHEMICAL FACTORS

WHICH CHANGE THE NUCLEOTIDE SEQUENCE OF DNA. SOME EXAMPLES OF MUTAGENS ARE IONISING RADIATION, HEAT, OR CARCINOGENIC CHEMICALS.

• LONG CHAINS OF NUCLEOTIDES MAKE UP DNA WHICH IS STORED IN THE NUCLEUS HOWEVER PROTEINS ARE ASSEMBLED

IN THE CYTOPLASM AT THE RIBOSOMES. IN ORDER FOR THE MESSAGE CODED ON A GENE, A SECTION OF DNA, TO BE TAKEN, TRANSCRIPTION INTO MRNA MUST OCCUR.  TO MAKE THIS MRNA, THE GENE IS READ THREE BASES AT A TIME WHICH IS CALLED TRIPLETS.  EACH TRIPLET ON DNA AND THE CORRESPONDING CODON ON MRNA CODE FOR A SPECIFIC AMINO ACID.  POINT MUTATIONS RESULT IN AN ALTERED WAY THAT THE DNA IS READ LEADING TO A POTENTIAL DIFFERENT AMINO ACID FOR WHICH IT CODES AND THEREFORE A POSSIBLE CHANGE IN THE PROTEIN. THIS COULD HAVE NEGATIVE OR POSITIVE EFFECTS ON THE STRUCTURE AND FUNCTION OF THE PARTICULAR CHANGED PROTEIN.

DESCRIBE THE DIFFERENT TYPES OF POINT MUTATIONS AND THEIR POSSIBLE EFFECTS ON PROTEIN STRUCTURE AND FUNCTION

• THERE ARE TWO SYSTEMS WHICH ARE USED TO CATEGORISE POINT MUTATIONS. IN THE FIRST SYSTEM, THE

MUTATION IS CATEGORISED AS A TRANSITION IF A PURINE BASE IS REPLACED WITH ANOTHER PURINE OR IF A PYRIMIDINE IS REPLACED WITH ANOTHER PYRIMIDINE BASE. TRANSVERSIONS ARE REPLACEMENTS OF ONE BASE TYPE (E.G. A PURINE) WITH THE OTHER (A PYRIMIDINE IN THIS CASE).

• IN THE FUNCTIONAL CATEGORISATION OF POINT MUTATIONS, THE MUTATION IS CHARACTERISED BY THE EFFECT IT HAS ON THE AMINO ACID SEQUENCE OF THE PROTEIN. THE DIFFERENT CATEGORIES FOLLOW:

• FREESE, E. (1959). THE DIFFERENCE BETWEEN SPONTANEOUS AND BASE-ANALOGUE INDUCED MUTATIONS OF

PHAGE T4. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 45(4), 622–633.

EXPLAIN THE BASIS OF SICKLE CELL ANAEMIA • BASE-PAIR SUBSTITION • NONSENSE MUTATION: A CODON FOR AN AMINO ACID IS REPLACED BY A TERMINATION CODON, THUS INTERRUPTING THE TRANSLATION PROCESS AT THAT POINT IN THE PROTEIN CHAIN. A SHORTER PROTEIN RESULTS.

• SILENT MUTATION: BECAUSE EACH AMINO ACID CAN BE CODED FOR BY MORE THAN NUCLEOTIDE SEQUENCE (64 CODONS

REPRESENT 20 AMINO ACIDS IN TOTAL) A CHANGE IN NUCLEOTIDE CAN RESULT IN A NEW CODON THAT CODES FOR THE SAME AMINO ACID. THE RESULTING PROTEIN IS IDENTICAL TO THE NORMAL PROTEIN HENCE IT WOULD HAVE THE SAME FUNCTION AND STRUCTURE OF THE ORIGINAL PROTEIN.

• MISSENSE MUTATION: A CODON FOR AN AMINO ACID IS REPLACED BY ONE FOR A DIFFERENT AMINO ACID. IN THIS CASE, A

DIFFERENT PROTEIN IS CREATED. THIS CATEGORY IS FURTHER SPLIT BASED ON THE EFFECT THE RESULTING PROTEIN HAS ON THE ORGANISM:

• IN CONSERVATIVE MUTATIONS THE PROPERTIES OF THE AMINO ACID AND THUS THE PROTEIN ARE SIMILAR TO THOSE OF THE ORIGINAL. •

THE QUATERNARY STRUCTURE OF THE PROTEIN IS SIMILAR ENOUGH TO HAVE THE SAME EFFECT AS THE ORIGINAL. AS A RESULT THE FUNCTIONING OF THE PROTEIN AND THE ORGANISM ARE NOT SIGNIFICANTLY CHANGED. IN NON-CONSERVATIVE MUTATIONS THE SUBSTITUTED AMINO ACID HAS DIFFERENT PROPERTIES THAN THE ORIGINAL, CAUSING THE PROTEIN TO LOSE OR CHANGE ITS FUNCTION. THIS FREQUENTLY RESULTS IN DISEASE AS THE QUATERNARY STRUCTURE IS CHANGED. FOR EXAMPLE, IN SICKLE-CELL DISEASE

DESCRIBE THE DIFFERENT TYPES OF POINT MUTATIONS AND THEIR POSSIBLE EFFECTS ON PROTEIN STRUCTURE AND FUNCTION

• BASE-PAIR INSERTIONS OR DELETIONS (FRAMESHIFT MUTATIONS) • DELETION: INVOLVES THE LOSS OF ONE BASE PAIR FROM THE DNA MOLECULE. AS THE BASES ARE READ

AS TRIPLETS, IF ONE PAIR GOES MISSING, THE WHOLE SEQUENCE WOULD BE READ DIFFERENTLY. HENCE IT IS CALLED A FRAME SHIFT.

• INSERTION: INVOLVES THE ADDITION OF A NEW PAIR OF BASES INTO THE DNA. IT IS SIMILAR TO

DELETION AS IT WOULD ALWAYS CAUSE A FRAME SHIFT. THIS WOULD RESULT IN A SERIOUS EFFECT ON THE PROTEIN WHICH IS MADE.

• EACH MUTATION LISTED ABOVE APART FROM SILENT MUTATION CAN PRODUCE A DIFFERENT AMINO ACID SEQUENCE (PRIMARY STRUCTURE) IN THE PROTEIN THAT THE DNA IS CODING FOR. CONSEQUENTLY, THE SECONDARY AND TERTIARY STRUCTURE OF THE PROTEIN WOULD BE DIFFERENT FROM THE ORIGINAL PROTEIN. THIS WOULD THEN LEAD TO THE PROTEIN’S STRUCTURE BEING DISRUPTED.

DESCRIBE THE DIFFERENT TYPES OF POINT MUTATIONS AND THEIR POSSIBLE EFFECTS ON PROTEIN STRUCTURE AND FUNCTION

FIGURE 1: DIFFERENT TYPES OF POINT MUTATIONS

DISCUSS THE ROLE OF EPIDEMIOLOGY IN UNDERSTANDING CAUSES OF ILL HEALTH AND THE SPREAD OF DISEASE

• DEFINITION: EPIDEMIOLOGY IS THE STUDY OF THE ORIGIN AND CAUSES OF DISEASES IN A COMMUNITY. IT IS THE

SCIENTIFIC METHOD OF INVESTIGATION PROBLEM–SOLVING USED BY DISEASE DETECTIVES EPIDEMIOLOGISTS, LABORATORY SCIENTISTS, STATISTICIANS, PHYSICIANS AND OTHER HEALTH CARE PROVIDERS, AND PUBLIC HEALTH PROFESSIONALS TO GET TO THE ROOT OF HEALTH PROBLEMS AND OUTBREAKS IN A COMMUNITY. WHY SHOULD WE STUDY OUTBREAKS? :

• OUTBREAKS ARE IMPORTANT PUBLIC HEALTH EVENTS AND MAY REPRESENT BREAKDOWNS IN PUBLIC HEALTH

MEASURES AND ALLOWS PREVENTATIVE MEASURES TO BE PUT IN PLACE TO PREVENT FUTURE OUTBREAKS OF THE SAME/SIMILAR DISEASES.

• OUTBREAKS ARE EXPERIMENTS OF NATURE AND PROVIDE AN OPPORTUNITY TO LEARN MORE ABOUT THE NATURAL HISTORY OF INFECTIOUS DISEASES.

DISCUSS THE ROLE OF EPIDEMIOLOGY IN UNDERSTANDING CAUSES OF ILL HEALTH AND THE SPREAD OF DISEASE • STEPS IN AN OUTBREAK INVESTIGATION : • VERIFY THE DIAGNOSIS - THIS IS IMPORTANT TO RULE OUT MISDIAGNOSIS AND LABORATORY ERROR. TO MAKE CERTAIN IT'S THE REAL THING, AND NOT A FALSE ALARM. THIS IS ESPECIALLY IMPORTANT IN HOSPITAL SETTINGS, BUT IN OTHERS AS WELL.

•  CONFIRM THE EXISTENCE OF AN OUTBREAK - THIS STEP REQUIRES YOU TO COMPARE THE MAGNITUDE OF THE PRESENT PROBLEM WITH SOME TYPE OF BASELINE. TO DO THIS, YOU NEED TO FIRST ESTABLISH A BASELINE; AND NEED TO CONSIDER, FOR EXAMPLE, WHETHER IT SHOULD BE THE PERIOD IMMEDIATELY PRECEDING THE CURRENT PROBLEM, OR THE CORRESPONDING PERIOD FROM THE PREVIOUS YEAR.

• IDENTIFY AND COUNT CASES - FOR THIS STEP YOU MUST FIRST ESTABLISH A CASE DEFINITION. A CASE

DEFINITION IS A STATEMENT WHICH SPECIFIES A PERSON WITH SOME SET OF SYMPTOMS AND/OR SIGNS AND/OR LABORATORY DIAGNOSIS WHICH OCCURRED DURING SOME TIME PERIOD USUALLY DEFINED AS THE OUTBREAK PERIOD. BASED ON THE CRITERIA IN THE CASE DEFINITION PERSONS SHOWING ONLY THESE WILL BE IDENTIFIED AS BEING EXPOSED TO THE OUT BREAK AND WILL BE COUNTED AS A CASE. ALL DATA IS COLLECTED DURING THIS STEP.

DISCUSS THE ROLE OF EPIDEMIOLOGY IN UNDERSTANDING CAUSES OF ILL HEALTH AND THE SPREAD OF DISEASE

• ORIENT DATA IN TERMS OF TIME, PLACE AND PERSON - THE FIRST STEP IN ORIENTING THE DATA IS

USUALLY TO CONSTRUCT A LINE LISTING. IN A LINE LIST EACH COLUMN REPRESENTS AN IMPORTANT VARIABLE, SUCH AS NAME, AGE, SEX, CASE CLASSIFICATION AND SO ON WHILE EACH ROW REPRESENTS A DIFFERENT CASE. THE LINE LIST CAN BE HAND-WRITTEN OR COMPUTER GENERATED. FOLLOWING THIS THE LINE LIST AND DATA COLLECTED IS USED TO CLASSIFY THE DATA IN TERMS OF TIME (EPIDEMIC CURVE), PLACE (SPOT MAPS) AND PERSON (COMPARE GROUPS).

• FORMULATE AND TEST HYPOTHESIS – IN MOST INVESTIGATIONS THE TIME, PLACE, AND PERSON

ORIENTATION PROVIDES ENOUGH INFORMATION TO DETERMINE HOW AND WHY THE EPIDEMIC STARTED. HOWEVER SOME CASES REQUIRE FURTHER INVESTIGATION. HYPOTHESES, BASED ON AVAILABLE DATA, WILL BE GENERATED TO EXPLAIN THE OUTBREAK IN ORDER TO DETERMINE TYPE OF EXPOSURE, AGENT, SOURCE OR RESERVOIR, MODE OF TRANSMISSION, OR RISK FACTORS.

DISCUSS THE ROLE OF EPIDEMIOLOGY IN UNDERSTANDING CAUSES OF ILL HEALTH AND THE SPREAD OF DISEASE

• CONDUCT ANIMAL OR ENVIRONMENTAL STUDIES TO DETERMINE THE SOURCE OF THE AGENT - THE TYPES OF

STUDIES INDICATED WILL DEPEND ON THE AGENT AND THE SUSPECTED MODE OF TRANSMISSION. FOR EXAMPLE FOODBORNE OUTBREAKS, ADDITIONAL INVESTIGATIONS OFTEN INCLUDE INSPECTION OF THE FOOD PREPARATION FACILITY. IF CONTAMINATION IS SUSPECTED TO HAVE OCCURRED PRIOR TO THE TIME OF FOOD PREPARATION A TRACE BACK INVESTIGATION MAY BE CONDUCTED.

• IMPLEMENT CONTROL AND PREVENTION MEASURES - AT THIS POINT MEASURES ARE PUT IN PLACE TO CONTROL THE OUTBREAK AND PREVENT ADDITIONAL CASES AND RECURRENCES OF THE PROBLEM. THESE MEASURES INCLUDE:

• 1) ELIMINATE THE SOURCE OR EXPOSURE OF SUSCEPTIBLE PERSONS TO THE SOURCE OF THE AGENT. E.G. REMOVE THE

SOURCE OF CONTAMINATION, REMOVE PERSONS FROM EXPOSURE, INACTIVATE OR NEUTRALIZE THE AGENT IN SOURCE, ISOLATE AND/OR TREAT INFECTED PERSONS.

• 2) INTERRUPT SPREAD FROM THE SOURCE TO SUSCEPTIBLE PERSONS, STERILIZE OR INTERRUPT ENVIRONMENTAL SOURCES OF SPREAD (WATER, FOOD, AIR), CONTROL MOSQUITO OR INSECT TRANSMISSION, IMPROVE PERSONAL SANITATION (WASH HANDS).

• 3) PROTECT SUSCEPTIBLE PERSONS E.G. VACCINATION, PROPHYLACTIC CHEMOTHERAPY.  • SOURCE : COURSES.WASHINGTON.EDU/ZEPI526/PAPERS09/INVESTIGATIONS