TOPIC 4: GENETICS
4.1 Chromosomes, genes, alleles and mutations
4.1.1; State that eukaryotic chromosomes are made of DNA and proteins
4.1.2: Define gene, allele, and genome
Gene
A heritable factor that controls a specific characteristic. A section of a DNA molecule that contains a
'genetic recipe' for making a particular protein.
Allele
One specific form of a gene, differing from other alleles by one or a few bases only, and occupying the same gene locus (location on a chromosome) as other alleles of the gene.
Genome
The whole of the genetic information of an organism.
4.1.3: Define gene mutation
An incorrect version of a gene caused by a copying mistake during DNA replication. A mutation can occur in one of three ways. 1) DNA polymerase fails to add one nucleotide (deletion) 2) DNA polymerase adds an extra nucleotide (addition) 3) DNA polymerase adds the wrong nucleotide (substitution). A substitution changes the sequence of only one codon, which in turn, may change the polypeptide that it codes for by one amino acid.
4.1.4: Explain the consequence of a base substitution mutation in relationship to the processes of transcription and translation (e.g. sickle cell anemia)

During DNA replication, DNA polymerase can sometimes make a mistake, called a gene mutation.

A mutation can occur in one of three ways: 1) DNA polymerase fails to add one nucleotide
(deletion); 2) DNA polymerase adds an extra nucleotide (addition); and 3) DNA polymerase adds the wrong nucleotide (substitution).

A substitution changes the sequence of only one codon, which in turn, may change the polypeptide that it codes for by one amino acid.

A mutation to one gene can result in a new form of the gene, called an allele. New alleles can be beneficial to a population but most mutations are either harmless or harmful.

Sickle cell anemia is a disease caused by a substitution to the 6th codon of a hemoglobin gene.

The mutant codon (GTG) codes for valine instead of the correct codon (GAG), which codes for glutamic acid.

The result is a slightly different structure of the hemoglobin molecule that is less efficient in
 transporting O2.
Sickle cell anemia individuals often experience heart and kidney damage that can be fatal; but sickle cell hemoglobin provides resistance to malaria.
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4.2 Meiosis
4.2.1: State that meiosis is a reduction division of a diploid nucleus to form haploid nuclei
4.2.2: Define homologous chromosomes
Chromosome pairs of the same size, with the same staining pattern, and with the same genes at the same chromosome loci. One homologous chromosome is inherited from the mother, the other from the father.
4.2.3: Outline the process of meiosis: pairing of homologous chromosomes, crossing over, two divisions, and 4 haploid cells

Meiosis is a special type of cell division concerned with producing sex cells (gametes).

Meiosis occurs in the sex organs of plants and animals.

Meiosis is a 2 step process with a first division (Meiosis I) and 2 second divisions (Meiosis II) that

 produce haploid gametes (eggs or sperm).
When two gametes fuse, in the process of fertilization, the diploid (2n) state is restored.
Meiosis is a reduction division. In other words, it is the division of a diploid (2n) cell resulting in two haploid (1n) daughter cells.

In a diploid cell there are two homologous chromosomes (2n).

In a haploid cell (gamete) there is only one of each chromosome (1n).
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4.2.4: Explain that non-disjunction can lead to changes in chromosome number, illustrated by reference to Down syndrome (trisomy-21)

Non-disjunction occurs when homologous chromosomes fail to separate at anaphase I, or when sister chromatids fail to separate at anaphase II.

The results of non-disjunction are gametes with too many or too few chromosomes.

A gamete with too few chromosomes can not survive, except in the case of a missing female sex chromosome (X).

A gamete with an extra chromosome is called a trisomy. Some types of trisomy are not lethal. For example, individuals with an extra chromosome #21 in every cell have a disorder called trisomy 21, which causes Down’s syndrome.

Observing chromosomes can reveal disorders. Karyotype analyses are performed to observe chromosomes. A karyotype analysis is performed using cells collected by chorionic villus sampling or amniocentesis, for pre-natal diagnosis of chromosome abnormalities.
Nondisjunction during Meiosis I
4.2.5: State that, in karyotyping, chromosomes are arranged in pairs according to their size and structure
4.2.6: State that karyotyping is performed with cells collected by CVS or amniocentesis for prenatal diagnosis of chromosome abnormalities
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4.2.7: Analyze a human karyotype to determine gender and whether non-disjunction has occurred
Karyotype of a Human Female Karyotype of a Human Male
Karyotype of a Human Female with Down’s Syndrome
4.3 Theoretical Genetics
4.3.1: Define genotype, phenotype, dominant allele, recessive allele, codominant alleles, locus, homozygous, heterozygous, carrier and test cross
Genotype
The alleles possessed by an organism.
Phenotype
The characteristics of an organism.
Dominant Allele
An allele that has the same effect on the phenotype in both the homozygous and heterozygous states.
Recessive Allele
An allele that does not affect the phenotype unless it is in the homozygous state.
Co-dominant Alleles
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Pairs of alleles both expressed in the heterozygous state.
Locus
The particular position of a gene on a particular chromosome.
Homozygous
Having two identical alleles (forms) of a particular gene.
Heterozygous
Having two different alleles (forms) of a particular gene.
Carrier
A person who has one copy of a recessive allele that causes disease in individuals homozygous for it.
Test Cross
Testing a suspected heterozygote by crossing it with a known homozygous recessive.
4.3.2: Determine the genotypes and phenotypes of the offspring of a momohybrid cross using a
Punnett grid

An easy way to calculate the expected outcome of a genetic cross is to draw a Punnet grid.

In a Punnet grid the possible types of gametes of the female parent are listed on the X axis and the possible types of gametes of the male parent are listed on the Y axis. If a parent is homozygous, he/she can only produce one kind of gamete. If a parent is heterozygous he/she can produce two kinds of gametes.
4.3.3: State that some genes have more than two alleles (multiple alleles)
4.3.4: Describe ABO blood groups as an example of codominance and multiple alleles

Some genes have multiple alleles. For example, there are three blood type alleles in humans.

Surprisingly, this does not mean that there are only three blood types in humans. Instead there are four: A; B; AB; and O.

The AB blood type results from codominance, a situation where both alleles are partially expressed in the heterozygous state.
Allele
Blood Type A
Blood Type B
Blood Type AB
Blood Type O
Accepted Notation
I A I A OR I A i
I B I B OR I B i
I A I B i i
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Sickle cell anemia – diseased Hb S
Sickle cell anemia – healthy Hb A

An immune response will occur if an individual receives a blood transfusion of an incompatible blood type.

Individuals with blood type A can receive a transfusion of blood type A and blood type O.

Individuals with blood type B can receive blood type B and blood type O.

Blood type AB can receive all blood types.

Blood type O is called the universal donor, and it can only receive blood type O.
A Punnet grid can be used to settle paternity disputes (i.e. which man is the father of a child)
4.3.5: Explain how the sex chromosomes control gender by referring to the inheritance of X and Y chromosomes in humans

There are 23 pairs of homologous chromosomes in humans. One of the homologous pairs is the sex chromosomes. The remaining 22 pairs of homologous chromosomes are called autosomal chromosomes.

In females, the two sex chromosomes are homozygous
(XX): they are large and they contain more than 300 different genes.

In males the two sex chromosomes are not homozygous
(XY): the Y is small and has only a few genes.

Gender is determined by the male gamete. If an egg is fertilized by an X sperm then the offspring will be female.
If an egg is fertilized by a Y sperm then the offspring will be male.
4.3.6: State that some genes are present on the X chromosomes and absent from the shorter Y chromosome in humans
4.3.7: Define sex linkage
Genes carried on the X chromosome.
4.3.8: Describe the inheritance of color blindness and hemophilia as examples of sex linkage
Sex-linked genes

Sex linked genes are genes that are carried on the X chromosome.
Carriers
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
Carriers are females that are heterozygous for recessive sex linked alleles.
Colour Blindness

Red Green color blindness is a recessive, sex-linked condition

Color blindness is more common in males than in females

Males cannot pass on color blindness to their sons since the Y chromosome does not have any of the colour blindness alleles

Females are less likely to be color blind than males because they must inherit two rare recessive alleles to express the disorder whereas males only need to inherit one.
Haemophilia

Haemophilia is a recessive, sex-linked genetic disorder; people with haemophilia are unable to produce clotting factor

There are no females with hemophilia because the hemophilia allele is homozygous lethal.
Therefore, only boys are born with hemophilia.

Males inherit the allele from their mother and develop the disease

Males can get haemophilia from a mother who is a carrier
Allele
Hemophilia – diseased
Hemophilia – healthy
Color blind
Accepted Notation
X h
X H
X b
X B Color vision
4.3.9: State that a human female can be homozygous or heterozygous with respect to sex-linked genes
4.3.10: Explain that female carriers are heterozygous for X-linked recessive alleles
Sex-linked genes

Sex linked genes are genes that are carried on the X chromosome. A human female has one of 3 possible genotypes for a sex linked trait:
 Homozygous dominant
 Heterozygous
 Homozygous recessive
Carriers

Carriers are females that are heterozygous for recessive sex linked alleles
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
Carriers have both the dominant and the recessive (disease) allele

Carriers do not have any symptoms of the disorder. Carriers can pass on the disorder to the next generation

Males cannot be carriers since they only have one X chromosome; a male is either healthy or diseased for sex linked diseases.
Sex-linked disorders

Color blindness and hemophilia are sex-linked disorders. Both disorders are more common in males than females because males only need to inherit one sex-linked allele to express the disorder but females must inherit two recessive alleles, which is less likely to happen.
4.3.11: Predict the genotypic and phenotypic ratios of offspring of monohybrid crosses involving any of the above patterns of inheritance
Complete the questions below:-
For full marks you must draw punnet grids to show your work.
A number of plant species have a recessive allele for albinism; homozygous albino (white) individuals are
unable to synthesize chlorophyll.
Predict the genotypic and phenotypic ratios of offspring for a self-pollinated tobacco plant heterozygous for albinism.
In human beings, brown eyes are usually dominant over blue eyes.
Suppose a blue-eyed man marries a brown-eyed woman whose father was blue-eyed. What proportion of their children would you predict to have blue eyes?
A brown-eyed man whose father was brown-eyed and whose mother was blue-eyed married a blueeyed woman whose mother and father were both brown-eyed. The couple has a blue-eyed son. What are the genotypes of all individuals?
In humans the blood groups are produced by various combinations of three alleles IA, IB, and i. Blood
type A is caused by either IA IA or IA i; type B by IB IB or IB i; type AB by IA IB; and type O by i i.
Suppose a child is of blood type A and the mother is of type 0. What type or types may the father belong to?
Suppose a father of blood type A and a mother of blood type B have a child of type O. What blood types are possible in their subsequent children?
Suppose a father of blood type B and a mother of blood type O have a child of type O. What are the chances that their next child will be blood type O? Type B? Type A? Type AB?
Suppose a father and mother claim they have been given the wrong baby at the hospital. Both parents are blood type A. The baby they have been given is blood type O. Could the parents be wrong? Could they be right? Explain.
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The allele of a form of color blindness is on the X chromosome. About 5 percent of males are color blind
but only about 1% of females are color blind.
A mother and father with normal color vision produce six male children, two of whom exhibit red-green colorblindness. Their five female children exhibit normal color vision. Explain the inheritance of redgreen colorblindness in their male children.
The alleles for eye color are only on the X chromosome of the fruit fly Drosophila. Red eye color (w+) is
dominant to white eye color (w).
What are the possible genotypes of a red-eyed female? What about a red-eyed male?
How many red-eyed offspring would you expect from the cross of a heterozygous female with a whiteeyed male?
How many red-eyed offspring would you expect from the cross of a heterozygous female with a redeyed male?
How many red-eyed offspring would you expect from the cross of a white-eyed female with a red-eyed male?
How many white-eyed offspring would you expect from the cross of a heterozygous female with a white-eyed male?
How many white-eyed offspring would you expect from the cross of a homozygous red-eyed female with a white-eyed male?
Hemophilia is a genetic disease x-linked disease made famous for its prevalence in royal families.
If a female carrier marries a man who is normal, what is the chance of their first daughter being a carrier? What is the chance of their first son being normal?
If a female hemophiliac (which is unlikely because females don’t normally survive with hemophilia) married a normal male then what percentage of their male offspring would be expected to have hemophilia?
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4.3.12: Deduce the genotypes and phenotypes of individuals in pedigree charts

A pedigree chart is used to show the inheritance of certain traits over several generations.

Before DNA technology they were used in genetic screening to predict the possible genotypes of offspring.
They are still used in this way because DNA technology is more expensive.

Couples can know the risk of having a baby with a particular genetic
 disorder, before it is conceived.
Below are some pedigree charts:
Chart A is for hemophilia; Chart B is for Color Blindness; Chart C is for an autosomal dominant gene;
Chart D is for an autosomal recessive gene. For each chart indicate the most likely genotype and phenotype of each white circle or square.
4.4 Genetic engineering and Biotechnology
4.4.1: Outline the use of polymerase chain reaction (PCR) to copy and amplify minute quantities of
DNA

DNA profiling requires thousands of DNA copies, sometimes from only a single DNA sample.

Polymerase chain reaction (PCR) is a procedure used to quickly multiply minute quantities of DNA for DNA profiling. This makes it possible to study DNA without the risk of using up a small sample
(for example a fragment of fossil). And it provides enough DNA to produce visible bands in gel electrophoresis.

PCR involves placing a DNA sample in a test tube that contains DNA polymerase and a large supply
 of nucleotides.
Then the temperature is raised to separate the two DNA strands; and then the temperature is cooled so that new nucleotides can attach to each single strand to make them double stranded. By
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alternating between warm and cold temperatures (15-20 times), huge quantities of DNA can be produced.

Once PCR has produced enough copies of the DNA sample, they are broken into fragments by restriction enzymes.

The DNA fragments are then analyzed using a procedure called Gel electrophoresis.
4.4.2: State that, in gel electrophoresis, fragments of DNA move in an electric field and are separated according to their size
4.4.3: State that gel electrophoresis of DNA is used in DNA profiling
4.4.4: Describe the application of DNA profiling to determine paternity and also in forensic investigations
DNA profiling to establish paternity

Because a person inherits DNA sequences from his/her parents, DNA samples can be used to establish paternity, maternity, and sibling relationships.

Parent-child DNA analysis has been used to help link adopted children with their biological parents and to resolve nursery room mix ups. It can also be used to confirm if a husband is, in fact, the biological father. In North America, about 10% of married fathers have been cuckolded (tricked into fathering a child that isn’t his own). When the truth comes out it can have significant emotional consequences for all family members; in most cases the family breaks up, which can have life-long effects on children.

Following natural disasters such as earth quakes and tsunamis, parents can become separated from their infants. Due to parental reactions to grief, it is not uncommon for a rescued infant to be claimed by more than one set of parents. In such cases, DNA testing can resolve conflicts.
DNA profiling to solve crimes

Criminals usually leave DNA at the crime scene. If the perpetrator gets wounded during a struggle then he may leave a blood stain that contains his DNA. If sex is involved then DNA can often be found in a semen sample. If a criminal urinates or spits at the crime scene then DNA can be found in the nuclei of bladder epithelial cells or inner cheek. At crime scenes, forensic scientists look for human hairs, which contain DNA when the hair follicle is attached.

Falsely convicted ‘criminals’ can be vindicated of wrong-doing. Numerous men serving life-sentences have been released from jail and cleared of charges when evidence was re-examined using new technology. For example, semen found on a rape-victims clothing can be analyzed even if the rape occurred several decades ago. When DNA in the semen matches the DNA of another suspect (one who wasn’t convicted of the murder) it indicates a false conviction.

When DNA evidence is based on old samples there is a chance of false information. Old DNA samples may be contaminated because of bacterial growth in the sample before it was collected.
Old samples may also break down and give incorrect results. These samples may have extra bands or missing bands in the gel.
4.4.5: Analyse DNA profiles to draw conclusions about paternity or forensic investigation

Because a person inherits DNA sequences from his/her parents, DNA samples can be used to establish paternity, maternity, and sibling relationships.

Parent-child DNA analysis has been used to help link adopted children with their biological parents and to resolve nursery room mix ups. It can also be used to confirm if a husband is, in fact, the
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biological father. In North America, about 10% of married fathers have been cuckolded (tricked into fathering a child that isn’t his own). When the truth comes out it can have significant emotional consequences for all family members; in most cases the family breaks up, which can have life-long effects on children.

Following natural disasters such as earth quakes and tsunamis, parents can become separated from their infants. Due to parental reactions to grief, it is not uncommon for a rescued infant to be claimed by more than one set of parents. In such cases, DNA testing can resolve conflicts.
DNA profile A: excludes an alleged father
DNA profile B: does not exclude an alleged father A real DNA Profile
4.4.6: Outline three outcomes of the sequencing of the complete human genome
The human genome project was a massive international effort that was undertaken to sequence the complete human genome. The project was completed recently at a total cost in the billions of dollars, with the intent to better our lives.
Benefits from the Human Genome Project

Improves our ability to conduct genetic screening for genetic disorders.

Improves our ability to develop new drugs for genetic diseases.

Improves our ability to use DNA in the study of evolution.

Improves our ability to develop new technologies (i.e. DNA sequencing)
4.4.7: State that, genes can be transferred between species - without changing the proteins they code for - because the genetic code is universal
4.4.8: Outline a basic technique used for gene transfer involving plamids/a host cell/restriction enzymes(endonucleases) and DNA ligase

Pieces of DNA can be transferred between species because the genetic code is universal (DNA has the same structure in all organisms).

Transferring pieces of DNA from one species to another can be achieved using a host cell. The bacterium E. coli is commonly used as a host cell for gene transfer. In addition to its circular DNA, E.
coli contains a much smaller ring of DNA called a plasmid.
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
Plasmids can be removed from a cell and broken apart using a restriction enzyme. Restriction enzymes recognize short DNA sequences and they cleave (cut) DNA molecules at these sites to produce DNA fragments, which may contain one or many genes.

Restriction enzymes are effective for gene transfer because they do not cleave ‘cleanly’. This means that at the ends of the DNA fragments, one strand is a few nucleotides longer than the other.

The DNA fragments have ‘sticky ends’ so they can join back together (by H-bonding) if they come close to one other. Once fragments have hydrogen bonded together, DNA ligase can be added to form covalent bonds.

A restriction enzyme is universal (it can be used to cleave DNA fragments in any species) so a DNA fragment from one organism may be inserted into a cleaved plasmid. Then the recombinant plasmid may be re-inserted into a cell. The recombinant plasmid then multiplies (forms clones) through normal cell divisions.

The human insulin gene has been transferred into E. coli in this way to produce insulin for diabetics.
4.4.9: List two examples of the current uses of genetically modified crops or animals

Golden rice is a variety of rice that has been genetically modified to produce beta-carotene (a precursor of vitamin A). Golden rice has the potential to prevent blindness or death in populations with vitamin A deficiency.

BT corn is a variety of corn that has been genetically modified to produce a bacterial toxin. The toxin is not harmful to people but it kills caterpillars. The advantage of BT corn is that it doesn't need to be sprayed with pesticides.
4.4.10: Discuss the potential benefits and possible harmful effects of one example of genetic modification

A relatively new application of DNA transfer is the development of transgenic plants and animals, also called genetically modified (GM) organisms. GM organisms contain one or more genes from a different species

Corn has been genetically modified to carry a gene from a BT bacterium that codes for a toxic protein. The GM corn produces the BT toxin, giving it protection from leaf-eating caterpillars.

Advantages of GM corn are: 1) it increases profits for farmers by saving them the expense of spraying pesticides; 2) it keeps the price of corn lower for consumers; and 3) it saves the environment from toxic pesticides, which can pose health risks to people and can kill non-target species that with important roles in the ecosystem.

Disadvantages are: 1) insect pests may develop resistance to the GM corn because continual exposure to the toxins will speed up the rate of natural selection; and 2) GM corn may produce toxic pollen, release it into the air, and harm beneficial species like the monarch butterfly(although recent studies do not support this claim).
4.4.11: Define clone
Genetically identical individuals.
4.412: Outline a technique for cloning using differentiated animal cells

A recent development in genetic research has been the cloning of mammals from a differentiated adult cell. A clone is a group of genetically identical organisms (or cells), artificially derived from a single parent.
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
Dolly the sheep, cloned in 1997 from a sheep’s udder, was the first successful clone from a differentiated adult mammalian cell. Scientists cloned Dolly by taking an unfertilized egg, removing its nucleus, and inserting a nucleus from a mammary gland cell.

Inside the egg, the mammary cell nucleus stopped behaving like the nucleus of a differentiated cell and it behaved like the nucleus of an undifferentiated cell. In other words, it behaved like an ordinary zygote nucleus.

The modified egg was then implanted into the uterus of another sheep, where it developed normally, and eventually became a baby sheep (with the same genotype as a living adult).

Livestock are more commonly cloned from undifferentiated cells. A fertilized egg is allowed to divide
3 times so that there are 8 identical cells. The 8 cells are separated and each is implanted into the uterus of a different surrogate mother. Several months later, 8 identical animals are born.
4.4.13: Discuss the ethical issues of therapeutic cloning in humans

Therapeutic cloning is the creation of an embryo to supply embryonic stem cells for medical use. An embryo can be created from potentially any cell in the human body by removing its nucleus and then implanting it into a human egg cell that has had its nucleus removed. Embryonic stem cell research has provided complete or partial therapies for certain cancers, some forms of blindness and chromosomal disorders. The therapies work by injecting millions of stem cells into the target tissue of the body. The stem cells must be compatible with the patient in order to avoid rejection by the patient’s immune system. New therapies are promising for spinal cord injuries and numerous diseases including Parkinson’s disease and multiple sclerosis.

Stem cell research has been the topic of passionate debate in recent years; primarily between religious groups and scientists. However there are different points of view amongst religious people and within the scientific community, so it is unfair to stereotype. Moreover, not all scientists are atheists; a small percentage of scientists are also religious.

Countries like China and Korea have been progressive in stem cell research. In countries like the
United States and England, stem cell research has been held back by governments that are influenced by religion; specifically, the belief that every embryo contains a ‘soul’. However, the
United States welcomes stem cell therapies arising in foreign countries; something some people see as hypocrisy.

Many religions make reference to the existence of a ‘soul’ within each human being; but many scientists doubt the existence of a ‘soul’ since a ‘soul’ cannot be observed or measured and hence there is no objective, evidence-based reason to believe in one. Some scientists add further that identical twins arise from a single fertilized egg several days after conception. Mockingly some ask,
“Did one soul split into two?” and “Does each twin have half a soul?”

Many religious people however, consider holy texts to contain ‘God-revealed truths’, and moreover, they believe it is ‘immoral’ or ‘sinful’ to question ‘Gods word’. Many scientists claim that there is no proof of god but there is proof of human suffering from disease. These scientists feel exasperated because they think that people’s beliefs in ‘ancient and fictitious myths’ are holding back treatments for ‘non-mythical real people’; people who have families and friends who will miss them when they die.

Some religious people say that the burden of proof is on scientists to show that there is no god and that there is no soul. However scientists reply that the onus is on religious people to provide evidence for their beliefs.
Removal of nucleus from human stem cell
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