# Genetics
## Chromosomes, genes, alleles, and mutations
### Define gene, allele, and genome.

* Gene: a heritable factor that controls a specific characteristic.
* Allele: a specific form of a gene.
* Genome: the complete set of an organism’s base sequences.

### Define gene mutation.

* Gene mutation: a random, rare change in genetic material.
* If DNA changes, RNA changes, which can change proteins, which affect structure and function.

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

* Base substitution: one base is replaced by another in the DNA sequence.
* Sickle-cell anaemia is caused by a mutation in the gene that codes for haemoglobin, a protein in red blood cells that is used for gas exchange.
* Normal GAG mutates to GTG; valine is added to the polypeptide chain instead of glutamic acid.
* Different peptide=altered structure=altered function.
* Different haemoglobin molecule shape changes structure of red blood cell so that it is sickle shaped.
* Symptoms: weakness, fatigue, and shortness of breath.
* Oxygen cannot be carried as efficiently by the sickle-shaped RBCs.
* Haemoglobin can crystallize within RBCs, making them inflexible; affected RBCs can clog capillaries.
* Mutated gene can be passed on to offspring.
* Those with sickle-cell anaemia are resistant to infection by malaria parasite.

## Meiosis
### State that meiosis is a reduction division of a diploid nucleus to form haploid nuclei.

* Haploid: n
* Diploid: 2n

### Define homologous chromosomes.

* Homologous chromosomes: chromosomes that carry the same genes, and therefore have similar shape and size.

### Outline the process of meiosis, including pairing of homologous chromosomes and crossing over, followed by two divisions, which results in four haploid cells.

‘‘’’Prophase I’’’’
* Chromosomes become visible as the DNA becomes more compact (supercoiling)
* Homologous chromosomes pair up
* Crossing over occurs
* Spindle fibres made from microtubules form
‘‘’’Metaphase I’’’’
* Bivalents (homologous chromosomes) line up across cell equator.
* Nuclear membrane disintegrates
‘’’’Anaphase I’’’’
* Spindle fibres attach to chromosomes and pull them to opposite poles of the cell.
‘‘’’Telophase I’’’’
* Spindles and spindle fibres disintegrate.
* Chromosomes uncoil and new nuclear membrane forms.
Cytokinesis now occurs. Cells are haploid, having only one chromosome of each pair. Each chromosome has its sister attached, so no S phase is necessary. Meiosis II takes place to separate sister chromatids. ‘’’’Prophase II’’’’
* DNA condenses into visible chromosomes again.
* New meiotic spindle fibres are produced.
‘’’’Metaphase II’’’’
* Nuclear membranes disintegrate.
* Individual chromosomes line up at the cell equator in random orientation.
* Spindle fibres from opposite poles attach to each sister chromatid at the centromere.
‘’’’Anaphase II’’’’
* Centromeres of each chromosome split, releasing each sister chromatid to become an individual chromosome.
* Spindle microtubules pull individual chromatids to opposite ends of the cell. Because of random orientation, chromatids can be pulled to either of new daughter cells.
‘’’’Telophase I’’’’
* Chromosomes uncoil into DNA strands.
Cytokinesis now occurs, yielding a total of four haploid cells.

### Explain that non-disjunction can lead to changes in chromosome number, illustrated by reference to Down syndrome (trisomy 21).

* Chromosomes do not always separate during first or second meiotic divisions, yielding an unequal distribution of chromosomes.
* In humans, this may give and egg or a sperm cell 24 chromosomes instead of 23.
* Caused by non-disjunction; chromosomes stick together instead of separating.
* Down syndrome is caused by non-disjunction in the 21st pair, and the child receives 3 instead of 2. This is a trisomy (tri-=3). Down syndrome is also called trisomy 21.
* Trisomy 21 brings malformations of the digestive system and differing degrees of learning difficulties.
* Down syndrome is most common chromosomal anomaly (1 in 800).
* Risk increases as age of mother increases, especially over age of 35.
* Non-disjunction can be severe enough to cause a miscarriage.

### Analyse a human karyotype to determine gender and whether non-disjunction has occurred.

* Large sex chromosome is X, small is Y.
* Three of one type means that non-disjunction has occurred.

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

* Genotype: symbolic representation of a pair of alleles possessed by an organism. Represented by two letters.
** Ex: Bb, GG, tt
* Phenotype: the characteristics or traits of an organism.
** Ex: five fingers on each hand, colour blindness
* Homozygous: having two identical alleles of a gene.
** Ex: AA is homozygous dominant
* Heterozygous:
* Dominant allele: allele that has the same effect on the phenotype regardless of what allele it is paired with.
** Ex: The genotype Aa gives the dominant A trait because the a allele is masked. The a allele is not transcribed and translated during protein synthesis. When labelling genotypes, capital letter indicates dominant, lower-case indicates recessive.
* Recessive allele: affects phenotype only when in the homozygous state.
** Ex: aa gives rise to the recessive trait because no dominant allele is there to mask it.
* Codominant alleles: pairs of alleles that both affect the phenotype when present in a heterozygote.
** Ex: parent with curly hair and a parent with straight hair have children with differing degrees of hair curliness; both alleles influence hair condition when both are present in the genotype.
* Locus: particular position on homologous chromosomes of a gene.
* Carrier: individual who has a recessive allele of a gene that does not have an effect on their phenotype.
** Ex: Aa carries the gene for albinism but has pigmented skin – an ancestor must have been albino and some offspring might be, too. If both parents are carriers, then some offspring may be affected (aa).
* Test cross: testing a suspected heterozygous organism by crossing it with a known homozygous recessive (aa). Since a recessive allele can be masked, it is often impossible to tell if an organism is AA or Aa until they produce offspring which have the recessive trait.

### Determine the genotypes and phenotypes of the offspring of a monohybrid cross using a Punnett grid.

Let:
* A = dominant allele, allows pigment to form
* a = recessive allele, albinism – few or no pigments
| Example | a | a |
| A | Aa | Aa |
| a | aa | aa |
Half the offspring are albinos, half are carriers of the albinism gene.

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

Let:
* I$^A$=allele for type A blood
* I$^B$=allele for type B blood
* i=recessive allele for type O blood
Therefore:
* I$^A$I$^A$ or I$^A$i gives a phenotype of type A blood
* I$^B$I$^B$ or I$^B$i gives a phenotype of type B blood
* I$^A$I$^B$ gives a phenotype of type AB blood
* ii gives a phenotype of type O blood
Genotype I$^A$I$^B$ shows codominance; neither allele is masked, both show expression in phenotype of blood type AB.

### Explain how the sex chromosomes control gender by referring to the inheritance of X and Y chromosomes.

* XX is female, XY is male
* This means that the chromosomes carried by the sperm will decide the gender of the offspring (egg always has XX)
* half of sperm contain one X and half have one Y
* 50% chance of being boy, 50% chance of being girl
| Example | X | X |
| X | Aa | Aa |
| Y | aa | aa |

### Define sex linkage.

* Any genetic trait whose allele has its locus on the X or the Y chromosome is sex linked.

### Describe the inheritance of colour blindness and haemophilia as examples of sex linkage.

* Colour blindness: inability to distinguish between certain colours.
** Allele for colour blindness found only on X chromosome
** X$^b$ = recessive allele for colour blindness
** X$^B$ = allele for the ability to distinguish colour
** X$^B$X$^B$ gives phenotype of non-affected female
** X$^B$X$^b$ gives phenotype of non-affected female that is a carrier
** X$^b$X$^b$ gives phenotype of an affected female
** X$^B$Y gives phenotype of non-affected male
** X$^b$Y give phenotype of affected male
* Haemophilia: disorder where the blood does not clot properly.
** Allele for haemophilia found only on X chromosome
** X$^h$ = recessive allele for haemophilia
** X$^H$ = allele for the ability to clot blood
** X$^H$X$^H$gives phenotype of non-affected female
** X$^H$X$^h$ gives phenotype of non-affected female that is a carrier
** X$^h$X$^h$ gives phenotype of an affected female
** X$^H$Y gives phenotype of non-affected male
** X$^h$Y gives phenotype of affected male
* Males are always affected if they have the recessive X allele.
* Females are more likely to be carriers than to have the condition.

### Explain that female carriers are heterozygous for X-linked recessive alleles.

* See 4.3.8.

### Deduce the genotypes and phenotypes of individuals in pedigree charts.
## Genetic engineering and biotechnology
### Outline the use of polymerase chain reaction (PCR) to copy and amplify minute quantities of DNA.

* In PCR, DNA is copied again and again to produce many (millions in a few hours) copies of the original molecules.
* Useful when very small amounts of DNA are found in a sample and larger amounts are needed for analysis.
* DNA from very small samples of semen, blood, or other tissue (even long-dead specimens) can be amplified using PCR.
* PCR is carried out at high temperatures using a DNA polymerase enzyme from ‘’Thermus aquaticus’’ (a bacteria that lives in hot springs).

### Describe the application of DNA profiling to determine paternity and also in forensic investigations.

* Many organisms (including humans) have short sequences of bases that are repeated many times (called satellite DNA).
** Satellite DNA varies greatly between different individuals.
* Samples containing satellite DNA can be copied using PCR, then cut into pieces using restriction enzymes; the lengths of fragments vary greatly between individuals.
* Gel electrophoresis can be used to separate fragmented pieces of DNA according to size and charge.
* This technique is called DNA profiling.
* Can be used in forensic investigations and obtaining paternity.

### Analyse DNA profiles to draw conclusions about paternity or forensic investigations.

* Profiles that match bands will most likely be from the same or related individuals.

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

* It will become easier to study how genes influence human development.
* It will allow easier identification of genetic diseases.
* It will allow the production of new drugs based on DNA base sequences or genes or the structure of proteins coded in these genes.
* It will give new insight into the origins of evolution and migrations of humans.

### Outline a basic technique used for gene transfer involving plasmids, a host cell (bacterium, yeast, or other cell), restriction enzymes (endonucleases), and DNA ligase.

* Prepare the gene for transfer.
** MRNA coding for insulin extracted from human pancreas cells that make insulin.
** DNA copies of the mRNA are made using reverse transcriptase.
** “Sticky” ends are made by adding extra G nucleotides to the ends of the gene.
* Prepare the plasmid (loop of bacterial DNA) to receive the gene.
** Plasmid is cut open using restriction enzymes (they cut open DNA at specific base sequences).
** “Sticky” ends are made by adding extra C nucleotides to the ends of the cut plasmid.
* Combine the prepared gene with the prepared plasmid.
** Ligase seals the nicks in the DNA by making sugar-phosphate bonds.
** Plasmid with insulin gene is called a recombinant plasmid.
* The recombinant plasmids are combined with suitable host cells, in this case E. coli.
* The GM E. coli are cultured in a fermenter.
* The bacteria start to synthesize insulin, which is extracted, purified, and used.

### State two examples of the current uses of genetically modified crops or animals.

* Bt maize that produces botulin toxin naturally, killing pests that would normally destroy the crop.
* GM salmon that have more muscle mass, and can therefore provide more food per fish.
* Plants that glow in the dark.

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

Example: Bt maize
| Potential benefits of Bt maize | Potential risks of Bt maize |
| Less pest damage and therefore higher crop yields to reduce food shortages. Less land needed for crop production (because of higher yield), so more natural area could be conserved. Less use of insecticide sprays, which are expensive and can be harmful to workers and wildlife. | Humans or animals eating the GM corn might be harmed by the bacterial DNA or Bt toxin in it. Insects that are not pests could be killed. Maize pollen will be blown onto wild plants near the maize; animals feeding on these wild plants may be affected. Populations of wild plants may be changed. Cross-pollination will spread the Bt gene into some wild plants, which will gain an advantage. |

### Define clone.

* Clone: a group of genetically identical organisms or a group of genetically identical cells derived from a single parent cell.

### Outline a technique for cloning using differentiated animal cells.

* Take differentiated cells from a donor animal.
** For example, udder cells from a sheep.
** These cells should be dormant (can be cultured in a low-nutrient medium to switch off genes).
* Take unfertilized egg cells from another animal.
** These egg cells should have their nuclei removed.
* Fuse the differentiated cells with the egg cells without nuclei using a pulse of electricity.
* These fused cells will develop like zygotes and become embryos.
* The embryos may be implanted into another sheep, which will become the surrogate mother.
* The offspring will be genetically identical to the animal that gave the differentiated cells.

### Discuss the ethical issues of therapeutic cloning in humans.

| Arguments for therapeutic cloning | Arguments against therapeutic cloning |
| Embryonic stem cells can be used for therapies that save lives and reduce suffering. Cells can be removed from embryos that have stopped developing, so would have died anyway. Cells are removed at a stage when embryos have no nerve cells and can feel no pain. | Every human embryo is a potential human being, which should be given a chance to develop. More embryos may be produced than are needed, so some may have to be killed. There is a danger of embryonic stem cells developing into tumour cells. |