Inherited Change

Learning Outcomes Candidates should be able to:

(a) [PA] describe, with the aid of diagrams, the behaviour of chromosomes during meiosis, and the associated behaviour of the nuclear envelope, cell membrane and centrioles (names of the main stages are expected, but not the sub-divisions of prophase); (b) explain how meiosis and fertilisation can lead to variation; (c) explain the terms locus, allele, dominant, recessive, codominant, homozygous, heterozygous, phenotype and genotype (see pages 3537 and 3941); (d) use genetic diagrams to solve problems involving monohybrid and dihybrid crosses, including those involving sex linkage, codominance and multiple alleles (but not involving autosomal linkage or epistasis);

Learning Outcomes Candidates should be able to:

(e) use genetic diagrams to solve problems involving test crosses; (f) [PA] use the chi-squared test to test the significance of differences between observed and expected results (the formula for the chi-squared test will be provided); (g) explain, with examples, how mutation may affect the phenotype; (h) explain, with examples, how the environment may affect the phenotype; (i) explain how a change in the nucleotide sequence in DNA may affect the amino acid sequence in a protein and hence the phenotype of the organism; (j) use the knowledge gained in this section in new situations or to solve related problems.

Sexual reproduction

Meiosis (Middle prophase I)

Meiosis (late prophase I)

Meiosis (Metaphase I)

Meiosis (Anaphase I)

Meiosis (Telophase I)

Meiosis (Meiosis II-Prophase II and Metaphase II)

Meiosis (Anaphase II)

Meiosis (Telophase II)

Meiosis

Meiosis

Meiosis

Meiosis I
During Interphase I double Chromosomes _________ 4n ie. 2n _____

During Prophase I thicken Chromosomes _________ ie. see _______________ sister chromatids homologous chromosomes _________ pair up ____________ bivalent / _________ synapsis ie. form _________ ie. may have __________ crossover at _________ chiasma
* crossovers only occur between NON-SISTER chromatids

breakdown Nuclear membrane _______________

Meiosis I
During Metaphase I Spindle fibers attach centromere to ___________ kinetochore (at ____________) homologous ____________chromosomes align at _________ equator ______

During Anaphase I shorten Spindle fibers _________ ____________ homologous chromosomes _________ separate move to opposite poles

Meiosis I
During Telophase I Each separated homologous chromosome reaches pole disappear Spindle fibers _________ reform Nuclear membrane _________ At this time, ~ cells may rest ~ cells may continue immediately into Meiosis II _________

meiosis and fertilisation can lead to variation

In sexually reproducing organisms, three processes lead to most genetic variation: 1. independent orientation (independent assortment )of chromosomes in meiosis (metaphase I) 2. crossing over of chromosomes in meiosis (late prophase I) 3. random fertilization

Independent orientation of chromosomes in meiosis and random fertilization lead to varied offspring

Homologous chromosomes can carry different versions of genes

Separation of homologous chromosomes during meiosis can lead to genetic differences between gametes
Homologous chromosomes may have different versions of a gene at the same locus One version was inherited from the maternal parent, and the other came from the paternal parent Since homologues move to opposite poles during anaphase I, gametes will receive either the maternal or paternal version of the gene

Differing genetic information on homologous chromosomes

Simplified example in mice: Coat color and eye color C (brown) c (white)
E (black) e (pink) Two possible outcomes for The genes

Crossing over (during late prophase I) further increases genetic variability

Genetic rearrangement between homologues Chiasma
Sister chromatid exchange
Site of crossing over Happens between chromatids within tetrads Genetic recombination

Produces new gene combinations

Can occur several times in various location within one tetrad

Zygote combination possibilities are much greater than 64 trillion Two individuals cannot produce identical offspring from separate fertilizations

Everyone is a unique genetic entity never seen before and never to be seen again

Figure: How crossing over leads to genetic recombination

Random fertilization
The combination of each unique sperm with each unique
egg increases genetic variability:
Combination 1 + Combination 2 is different from Combination 3 + Combination 4, etc.

Paper 4 JO5
Figure is a diagram of pair of homologous (c) Explain how this can lead to variation. [2] chromosomes during meiosis.
- breakage of linkage groups / ref. new linkage groups ; - may have different alleles ; - creates new combinations of alleles ; - when sister chromatids separate ;

(d) Describe two other sources of variation that (a) State the stage of meiosis shown. [1] are possible as a result of meiosis. [4] metaphase 1 / (late) prophase 1 - idea of random orientation at metaphase I and II / random alignment of homologous chromosomes on spindle equator ; (b) Describe what has occurred between the - subsequently leads to independent two homologous chromosomes. [3] assortment ; - homologous chromosomes) pairing / - 2n possible combinations when n is synapsis number of chromosome pairs ; - to chiasma / crossing over - ref. to chromosome mutation qualified ; - exchange of genetic material - ref. gametes haploid (so can fuse) ; - between non-sister chromatids - random fusion of gametes ;

Important terms
Locus- a locus (plural loci) is the specific location of a gene or DNA sequence on a chromosome. Allele- a different form of gene (e.g. represented with letters for the different types of alleles PP, Pp, pp) Dominant- allele that always expresses itself in the phenotype when present/ allele which influences the phenotype even in the presence of a alternative allele. Recessive- allele which does not have its effect in heterozygote/ allele which only effect in homozygotes/ affects phenotype if dominant allele is absent.

Important terms
Codominant- both alleles, influence phenotype/ are expressed; more than 2 phenotypes possible; phenotype of heterozygote different from either homozygote Homozygous- having two identical alleles of gene (PP, pp) Heterozygous- having two different alleles of gene (Pp) Phenotype- the observable characteristics of an organism,

Genotype- the alleles possessed by an organism

Gene loci
P a B

Dominant allele

P Genotype: PP Homozygous for the dominant allele

a aa Homozygous for the recessive allele

Recessive allele

Bb Heterozygous

Figure: Matching gene loci on homologous chromosomes.

Test cross
Test cross always involves crossing an organism showing the dominant phenotype with one which is homozygous recessive.

Paper 4 (J09)
The inheritance of coat color in horses is complex but all horses have one of two base colors, red (chestnut) or black. The base color is controlled in a simple monohybrid way.

Draw a genetic diagram to show how two parents with black coat color can produce a chestnut foal and the probability of such an event occurring. Choose a letter symbol to represent coat color. [4]

Paper 4 (N04)
Figure shows four generations of a family in which some members of the family suffer from sickle cell anaemia.
Using the symbols HN for the allele for normal haemoglobin and HS for the allele for sickle cell haemoglobin, state the genotypes of the following individuals. [1] A: ______________________________ C: ______________________________ Draw a genetic diagram to show the probability of the parents A and B producing another child with sickle cell anaemia. [4]

Multiple alleles
Most genes have more than two alleles, e.g. human blood groups. The four groups A, B, AB, O are all determined by a single gene. Three alleles of this exist IA, IB, and IO. IA, IB are codominant, while IO is recessive to both IA, IB . A diploid cell can carry only two alleles, the possible genotypes and phenotype are shown in table 17.2.

Sex inheritance
The X chromosome contains many different genes. One of them is a gene that codes for the production of a protein needed for blood clotting, called factor VIII. There are two alleles of this gene, the dominant one H producing normal factor VIII, and the recessive one h resulting in lack of it. People who are homozygous for the recessive allele suffer from the disease haemophilia, in which the blood fail to clot properly. This gene is on the X chromosome, and not on an autosome, affects the way that it is inherited. Females, who have two X chromosomes, have two copies of the gene. Males, have one copy of the gene. Therefore, the possible genotypes for men and women are different. Sex linked- is found on a part of the X chromosome not matched by the Y, and therefore not found on Y chromosome.

Paper 4 (J08)
Color blindness is a condition characterized by the inability of the brain to perceive certain colors accurately.
(a) Explain the meaning of the terms allele and recessive. [2] Allele: Recessive: (b) Explain why females are less likely than males to have RGC. [2] (c) With reference to the figure, and using the symbols R for dominant allele and r for the recessive allele, state the genotypes of the individuals 1, 4, 6 and 7. [4]

Dihydrid crosses (ratio 1:1:1:1)

Dihybrid crosses look at the inheritance of two genes at once. In tomato plants, there is gene which codes for stem colour. This gene has two alleles:

A different gene, at a different locus on a different chromosomw, codes for leaf shape. There are two alleles:

Dihydrid crosses (ratio 1:1:1:1)

What will happen if a plant which is heterozygous for both of these genes is crossed with a plant with green stem and potato leaves?

At fetilisation, any of four type of gamete from the heterozygous parent may fuse with the gametes from the homozygous parent. The genotypes of the offspring will be:

Dihydrid crosses (ratio 1:1:1:1)

From this cross, we would expect approximately equal numbers of the four possible phenotypes. This 1: 1: 1: 1 ratio is typical of a dihybrid cross between a heterozygous organism and a homozygous recessive organism, where the alleles show complete dominance.

Dihydrid crosses (ratio 9:3:3:1)

If both parents are heterozygous. There are sixteen possibilities. 9 purple, cut: 3 purple, potato: 3 green, cut 1 green, potato 9:3:3:1 ratio This is typical dihydrid cross between two heterozygous organism.

Dihydrid crosses

Paper 4 (J06)
The summer squash plant produces fruits that are either white of yellow in color and are either shaped like a disc or a sphere. The dominant phenotypes are white and discshaped fruit. Using the symbols A for white and a for yellow and B for disc and b for sphere, draw a genetic diagram to show what proportion of offspring will have yellow and sphere-shaped fruit if a white and disc-shaped fruit plant, heterozygous for both genes, is self fertilized. [6]

Paper 4 (J07)
Another gene may cause strips A gene for feather color in on feathers (barred feathers). chickens is carried on an This gene is carried on the X autosome. This gene has two chromosome. The allele for alleles, black (CB) and splashedbarred feather (XA) is dominant white (CW). When a male to the allele for non-barred chicken with black feathers is feathers (Xa). In chickens the mated with a female chicken male is homogametic and has with splashed-white feathers, two chromosomes while the all the offspring have blue female is heterogametic and feathers. This also occurs when has one X chromosome and one a male chicken with splashedY chromosome. white feathers is crossed with a female with black feathers.

Paper 4 (J07)
A male chicken with black, non-barred feathers was crossed with a female chicken with splashed-white, barred feathers. All the offspring had blue feathers, but the males were barred and the females were non-barred. Using the symbols given above, draw a genetic diagram to show this cross. [5] Explain how a farmer could use a breeding program to find out the genotype of a male chicken with blue, barred feathers. [3]

Paper 4 (J07)

The

2 X

(Chi-squared) test

Two plant produced a total of 144 offspring. If the parents really were both heterozygous, and if the purple stem and cut lead alleles really are dominant, and if the alleles really do assort independently, then we would expect the following numbers of each genotype to be present in the offspring:

But image that, amongst these 144 offspring, the results we actually observed were as follows: Purple, cut 86 green, cut 24 purple, potato 26 green, potato 8

The

2 X

(Chi-squared) test

We might ask, are these results sufficiently close to ones we expected that the differences between them have probably just arised by change, or are they so different that something unexpected must be going on? We can use a statistical test called the X2 (Chi-squared) test. This results allows us to compare our observed results with the expected results, and decide whether or not there is a significant difference between them. The first stage in carrying out this test is to work out the expected results, as were have already done. These, and the observed results, are then recorded in table like the one overleaf. We then calculate the difference between each set of results, and square each different. (squaring it get rid of any minus signs- it is irrelevant whether the differences are negative or postive)

The X2 (Chi-squared) test

Then we divide each squared difference by the expected value, and add up all of these answer:

The

2 X

(Chi-squared) test

Now we have X2 value. We look in a table that relates X2 values to probabilities. The probability given in the table are

E.g. a probability of 0.05 means that we would expect these differences to occur in 5 out of every hundred experiments, or 1 in 20 just by chance. In biological experiments, we usually take a probability of 0.05 as being the critical one. If X2 value represents a probabilities of 0.05 or larger, then we can be fairly certain that the differences between our observed and expected results are due to chance- the differences between them are not significance.

The

2 X

(Chi-squared) test

There is one more aspect of our result to consider, before we look up our value of X2 in the table- degree of freedom. This takes into account the number of comparisons made. (Remember that to get our value of X2 , we added up all our calculated values, so obviously the larger the number of observed and expected values we have, the larger X2 is likely to be, we need to compensate for this) To work out the number of degrees of freedom, simply calculate the (number of classes of data-1). (4-1)= 3 We can look a the table to determine whether our results show a significant deviation from what we expected.

The X2 (Chi-squared) test

Our calculated value is 0.79, the value is a much smaller value than the one we have read from the table. It would be way off the left hand side, representing a probability of much more than 0.1 (1 in 10) that the difference in our results is just due to chance. So we can say that the difference between our observed and expected results is almost certainly due to chance, and there is no significant difference between what we expect, and what actually got.

Paper 4 N09
Complete the missing values in the table. [3]

Table below relates chi-square values to probability values. As four classes of data were counted, the number of degrees of freedom was 4-1=3. Table gives values of chi-square where there are three degrees of freedom.

Calculate the value for chisquare. [1]

Explain whether or not the observed results were significantly different from the expected results. [2]

Mutation
Mutation- an unpredictable change in the genetic material
of an organism. 2 type of mutation 1. Gene mutation- a change in the structure of a DNA molecule, producing a different allele of a gene. 2. Chromosome mutations- mutation changes in the structure of or number of whole chromosomes in a cell. Mutations may occur completely randomly with no obvious cause, but there are several environment factors that significantly increase the chances of a mutation occurring (mutagen) 1. ionising radiation- (, , ) 2. Ultraviolet radiation Note: Mutagen- a substance that can cause mutation.

Mutation (gene mutation)

Addition

Mutation (gene mutation)

Base additions or deletions usually have a very significant effect on the structure, because they alter every set of three bases that follow them in the DNA molecule. Therefore the function, of the polypeptide that the allele codes for. They are said to cause frame shifts in the code. It may introduce a stop triplet part way through a gene, so that a complete protein is never made at all. Base substitution may have no effect at all. A mutation that has no apparent effect on an organism is said to be a silent mutation. E.g. CCT to CCA or CCG makes still make Gly. However, base substitution can be very large effect. E.g. base sequence ATG (coding for Tyr) mutated to ATT, this has produced a stop triplet, so the synthesis of protein would sop at this point.

Sickle cell anaemia

Mutation due to base substitution at the gene that codes for polypeptide chains of haemoglobin CTT which codes for glutamic acid mutates to CAT which codes for valine Mutant polypeptide chains are less soluble and forms fibres in RBCs Sickle-shape Inefficient in O2 transportation and get stuck in blood capillaries

Sickle cell anaemia

Recessive allele HS codes for the production of mutant polypeptide chains that causes sickle RBCs HSHS Sickle cell anaemia HNHS Carrier HNHN Normal Common in Africa

Sickle cell anaemia and malaria

In malarial region, carriers of sickle cell allele (HNHS) can survive better, so HS allele is frequent HSHS Die from sickle cell anaemia HNHN Die from malaria HNHS Not suffer from sickle cell anaemia and less likely to suffer from malaria Able to reproduce and pass on the HS allele Selective advantage

Phenylketonuria (PKU)
Phenylketonuria (PKU) a genetic disease resulting from a mutation from in gene that codes for an enzyme involved in the metabolism of Phenylketonuria. Mutation happens on gene that codes for production of enzyme phenylalanine hydroxylase Complications of PKU: Less melanin Lighter skin and hair colour Phenylalanine accumulates in blood and tissue fluid which cause mentally retarded and brain damage in children. Phenylalanine hydroxylase Phenylalanine tyrosine melanin

Converted into Malanin

Phenotype affected by both environmental and Gene

1. Diet and nutrients - Height and weight 2. Low temperature - Dark fur color on Himalayan rabbits 3. High temperature - Gender of reptiles 4. Ultraviolet rays - Production of melanin 5. Wavelength of light - Flowers and fruit color

Production of Insulin
Injection of insulin is needed for diabetes mellitus patients Insulin extracted from animal sources is expensive, has side-effects and ethical / religious issues Therefore, production of insulin through genetic engineering is encouraged

Production of Insulin
1. Isolating the insulin gene - mRNA for insulin extracted from cells (human pancreas) - Incubate mRNA with reverse transcriptase enzyme - Complementary DNA (cDNA) is formed - DNA polymerase is added to form complete doublehelix structure

Production of Insulin
2. Inserting the gene into a vector - Vector Small carrier in which fragments of DNA can be inserted, eg. Plasmid - Plasmids are centrifuged and isolated from bacteria - Enzyme restriction endonuclease is used to cut the plasmids with sticky ends - DNA ligase to join insulin gene into plasmids Recombinant DNA

Production of Insulin

3. Inserting the gene into the bacteria - Plasmids with recombinant DNA mix with bacteria - Bacteria that take up plasmids are isolated and cultured in large scale - Extraction and purification of recombinant insulin

Production of Insulin

Uses of gene technology

Medical: Synthesis of growth hormones, recombinant Factor VIII to treat haemophiliac and production of pharmaceutical drugs. The human gene for making factor VIII has been inserted into hamster kidney and ovary cells that are then cultured in fermenters. The cells constantly produce factor VIII, which is extracted and purified before being used to treat people with hemophilia. Before availability of the recombinant factor VIII, came from human and this carried risks of infection, such as HIV. Agriculture: Genetically modified crops against pests and insecticides, genetically modified organisms with desirable traits and better yields Industry: Biological washing powder and production of genetically modified food