Topic 4: Genetics

Chromosomes, alleles and mutations

4.1.4 Explain the consequence of a base substitution mutation in relation to the processes of transcription and translation, using the example of sickle-cell anemia.

• Sickle cell anemia caused by base substitution mutation
• of gene coding for β-globin polypeptide in hemoglobin   from CTC to CAC.
• After transcription, mRNA strand will have codon GUG instead GAG
• During translation, GUG codes for amino acid valine instead of glutamic acid
• Chains of mutated hemoglobin molecules stick together to distort red blood cells into a sickle shape
• High-oxygen conditions cause hemoglobin chains to break up and blood cells return to normal shape
• This damages blood cells and reduces their life span to only 4 days.
• Body is unable to replace red blood cells fast enough and anemia develops.
• Sickle-shaped blood cells can also block narrow blood vessels, restricting blood flow which could lead to heart disease.

Theoretical genetics

4.3.1 Define genotype, phenotype, dominant allele, recessive allele, codominant alleles, locus, homozygous, heterozygous, carrier and test cross.

Genotype - Alleles of an organism

Phenotype - Characteristics of an organism

Dominant allele - Allele that has the same effect on the phenotype whether the individual genotype is homozygous or heterozygous

Recessive allele - Allele that only has an effect on the phenotype when present in the homozygous state

Codominant alleles - Pairs of alleles that both affect the phenotype when present in a heterozygote

Locus - Particular position of a gene on homologous chromosomes

Homozygous - Having two identical alleles of a gene

Heterozygous - Having two different alleles of a gene

Carrier - Individual with one copy of a recessive allele that causes a genetic disease in individuals that are homozygous for that allele

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 monohybrid cross using a Punnett grid

4.3.3 Some genes have more than two alleles (multiple alleles).

4.3.4 Describe ABO blood groups as an example of codominance and multiple alleles.

• Codominance occurs when both alleles present in the genotype have an effect on the phenotype.
• This is true for blood group AB as alleles IA and IB are both fully expressed.
• Multiple alleles occurs when there are more than two different alleles for the same gene coding for on characteristic.
• Some genes have more than two alleles. This is true for blood groups A and B.
• Individual with blood group A either has genotype IAi or IAIA
• Individual with blood group B either has genotype IBi or IBIB
• Blood groups A and B are spread between members of the human population.

4.3.8 Describe the inheritance of colour blindness and hemophilia as examples of sex linkage.

[Nov 2012] Describe the inheritance of hemophilia including an example using a Punnett gird. [6 marks]

Hemophilia is sex-linked, since it is located on the X chromosome (sex chromosome).

For this reason, hemophilia is more common in males who only receive one chromosome. A female is hemophilic if she is homozygous recessive for the hemophilia allele, moreover the condition of being homozygous recessive is normally fatal. Therefore females are usually carriers of the hemophilia allele. Conversely, sex linkage is important in males because the allele present on the X chromosome is always expressed, due to the absence of the gene on the Y chromosome. This is illustrated in the punnet grid below, where X^H  represents the dominant normal allele, and X^h indicates a recessive hemophilia allele:

As shown in punnet grid, half the male offspring have hemophilia, whereas half the female offspring are hemophilia carriers.

Sex-linkage refers to the mode of transmission of genes present on the sex chromosome, mainly the X chromosome. Sex linkage is important in males because the allele present on X chromosome will always be expressed because of the absence of the allele on the shorter Y chromosome. This can be explained using the example of red-green colour blindness. When the recessive X^b allele is present in the genotype of males, it is always expressed because it is absent on the Y chromosome. This is because the Y chromosome carries only genes specific for sex determination and sperm production. Females on the other hand can be homozygous or heterozygous with respect to sex-linked genes. This means that they can be carriers because the dominant allele for normal colour vision can be mask the recessive allele for red-green colour blindness (X^bX^B).

4.3.9 A human female can be homozygous or heterozygous with respect to sex-linked genes.

4.3.11 Predict the genotypic and phenotypic ratios of offspring of monohybrid crosses involving any of the above patterns of inheritance.

4.3.12 Deduce the genotypes and phenotypes of individuals in pedigree charts.

Meiosis

4.2.1 Meiosis is a reduction division of a diploid nucleus to form haploid nuclei.

4.2.2 Define homologous chromosomes.

Homologous chromosomes - Chromosomes with the same length, carrying the same genes each at the same locus.

Describe karyotyping and one application of its use.

• Cells undergoing mitosis are obtained in karyotyping, either through chorionic villus sampling or by amniocentesis.
• Mitosis is stopped during metaphase and photographs are taken.
• Chrosomes are cut out from photograph and arranged into homologous pairs according to similar structure.
• Karyotyping can be used to identify abnormalities in the number of chromosomes
• Individuals with a genetic disorder such as Down syndrome can be identified by determining if an extra chromosome is present.
• Karyotyping can also be used to determine gender, by identifying whether a Y chromosome is present or not.

4.2.3 Outline the process of meiosis.

Meiosis is a reduction division of a single diploid cell to form four haploid cells/gametes which are genetically different to their parents. Meiosis begins with prophase I of meiosis I, whereby the homologous chromosomes pair up and line-up at the equator. The spindle fibres then pull homologous chromosomes to opposite poles and two hapolid cells result. The second division, similar to mitosis, separates the chromatids to opposite poles, and four haploid cells result.

two cell divisions / reduction-division / diploid to haploid / meiosis I and meiosis II; produce four (haploid) cells; for production of sex cells / gametes; that are different from parent cells;

homologous chromosomes / two chromatids pair up;

line-up on equator;

(spindle fibres) pull homologous chromosomes to opposite poles;

two haploid cells are formed;

second division / like mitosis, separates chromatids to opposite poles;

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 due to non-disjunction during meiosis.
• This occurs when a homologous chromosome pair fails to move to the opposite pole.
• Instead this homologous chromosome pair moves to the same pole so that when the diploid cell separates into two cells, one cell has an extra chromosome.
• For this reason, after the second the division one cell will have an ectra chromosome.
• Alternatively, during anaphase II of meiosis, a homologous chromsome can fail to separate so that one cell out of the four cells has an extra chromosome.

cells undergoing mitosis are used for karyotyping;
Karyotypes are obtained using chorionic villus sampling or aminocentesis.
process of mitosis is stopped at metaphase;
chromosomes (cut from photographs) are arranged in homologous pairs of similar
structure
allows abnormalities in the chromosome number to be identified
For example gender can be determined as well as down syndrome
which is detected by identifying whether an extra chromosome is present.

Discuss the ethical issues of genetic screening

Genetic screening involves testing for the presence or absence of certain genes. Genetic screening can be used in the process of in vitro fertilization to select embryos that do not have a genetic disorder. In addition, parents can choose not to have a child if a genetic disease is identified in the embryo, which would mean that fewer children with a genetic disorder are born. The downside to this however is that the rate of abortions would increase, which many argue is the same as killing a human.
For this reason, some parents choose to have a child with a genetic disorder and through the use of genetic screening are able to plan treatments such as gene therapy for the child, to prevent symptoms from occurring.
Other potential uses of genetic screening are controversial. Genetic screening of chromosomes can involve karyotyping, which can be used to identify gender of an embryo. Parents could select embryos in IVF or choose not to give birth to a child of a specific gender, which some individuals say is against "God's will".
Genetic screening can also be used by adults to check if they have a genetic predisposition for a certain genetic disorder. The downside to this is that it can cause deep psychological suffering and possibly result in the denial of health insurance.

 genetic screening is testing for the presence or absence of gene / 
chromosome;
screening for chromosomes can involve karyotyping;
genetic screening is controversial;
advantages: [4 max]
parents can choose to avoid having children with disorder;
parents can prepare for a child with a disorder;
parents can use IVF to select embryos that are normal;
can use gene therapy to correct the problem;
treatment can start to prevent symptoms;
fewer children with the disorder are born;
disadvantages: [4 max]
frequency of abortion can increase;
parents can select embryos for sex of the child;
can have harmful side effects such as depression if you know you will
develop a disorder later;
can create a genetic underclass;
health insurance / treatment can be denied if there is genetic predisposition;

Genetic engineering and biotechnology

4.4.1 Outline the use of polymerase chain reaction (PCR) to copy and amplify minute quantities of DNA. 

4.4.1 Outline the use of polymerase chain reaction (PCR) to copy and amplify minute quantities of DNA.

PCR can multiply and amplify minute quantities of DNA by heating and cooling the DNA and using DNA polymerase which add nucleotides to the separated DNA strands.

1.       DNA is heated to denature and separate DNA DNA double helix.

2.       Primers, polymerase and nucleotides are added using DNA polymerase.

3.    Temperature is lowered slightly to allow annealing of the primers to DNA.

4.    DNA polymerase from a bacterium adapted to high temperatures used to replicate DNA at a higher temperature.

5. Process is repeated approximately 20 times.

6. Processes take place in thermal cycler which repeats the three required temperatures.

PCR is used when large quantities of DNA sample are needed, e.g. crime investigations.  DNA can be extracted from blood, semen, skin tissues and etc.

4.4.6 Outline three outcomes of the sequencing of the complete human genome.

• Knowledge of position of human genes on chromosomes
• knowledge of the mechanism of mutations
• greater potential for drugs to be designed to treat genetic diseases.

knowledge of location of human genes / position of human genes on
chromosomes;
knowledge of number of genes/interaction of genes / understanding
the mechanism of mutations;
evolutionary relationships between humans and other animals;
discovery of proteins / understanding protein function / detection
of genetic disease;
leads to the development of medical treatment/enhanced research
techniques;
knowledge of the base sequence of genes/study of variation within genome;

4.4.10 Discuss the potential benefits and possible harmful effects of one example of genetic modification.

Bt cotton is a genetically modified crop that contains the gene from the bacterium Bt that produces a toxin which kills insects, mainly the cotton bullworm, that consume the plant. The cotton bollworm is a damaging pest in the major cotton growing countries of the world.

Chemical pesticides used to eradicate this pest are expensive, damaging to the environment and to human health.
Bt cotton has a higher yield than non-GM cotton is requires less pesticides, thereby reducing the costs and damage to the environment and human health.

Bt cotton kills only insects that feed on it, so other insects and animals are unaffected. 

However, insects such as the bullworm that do feed on Bt cotton may develop resistance to the toxin in Bt cotton in the future, which has already occurred in some regions in India.

In addition, Bt cotton can potentially affect the gene pool of other cotton plants, although studies so far have shown that this has not yet occurred and countries with wild cotton plants have banned the cultivation of Bt cotton.

4.4.11 Define clone.

Clone - Group of genetically identical organisms derived from a single parent cell.

4.4.12 Outline a technique for cloning using differentiated animal cells.

Cloning is a process whereby genetically identical organisms is produced from a single parent cell through non-sexual means.

This can be explained using the example of Dolly the sheep which was produced via nuclear transfer techniques. Dolly was produced from fully differentiated cells in the udder of an ewe. These isolated cells were cultured in a medium low in nutrients, depriving the cells and causing genes to become quiescent. 

An unfertilized egg cell was taken from a different ewe, and after the nucleus was removed the egg cell without a nucleus fused together with the cultured udder cells, using an electric pulse. This electric pulse also instigated cell division, resulting in the formation of an embryo.

This embryo was then implanted in the uterus of the surrogate mother ewe. After 148 days of gestation, dolly (who was genetically identical from the ewe from which the nucleus was taken) was born.

In case you had difficulty understanding the above, the steps below summarize this complex but straightforward method of cloning.

1. Differentiated (specialized) udder cells taken from a 6-year old ewe (female sheep).

2. Cultured in medium that deprived cells of essential nutrients, thereby causing genes to become quiescent (inactive).

3. Unfertilized egg cell obtained from different ewe.

4. Nucleus of unfertilized egg cell removed using a micropipette.

5. Unfertilized egg cell with no nucleus fused together with differentiated udder cell from other ewe, using an electric impulse.

6. Electric impulse used to trigger mitosis (cell division), resulting in an embryo (unborn organism).

7. Embryo implanted into uterus of surrogate (substitute) mother.

8. After 148 days of gestation, Dolly the sheep was born. Dolly was genetically identical to the ewe from which the nucleus was obtained.

Outline the ethical issues of therapeutic cloning.
Therapeutic cloning involves the production of embryonic stem cells that can be used for medical treatment.
Embryonic stem cells obtained can be transplanted into patients suffering from leaukemia and other degenerative diseases. In addition, embryonic stem cells can be obtained from embryos that have stopped developing, which would die in any case. The process of taking embryonic stem cells from an embryo is painless because the embryo has no nervous system. However, therapeutic cloning also involves the creation of excess embryos that are killed off, which some compare to the killing of a human life.
If embryos are not produced they can form a race of human clones which can result in a human underclass that are not treated like normal humans.
Lastly, therapeutic cloning can result in embryonic stem cells forming tumours, which is highly dangerous for patients already suffering from degenerative diseases.