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Unit 3:Genetics

core

Rana Al Liddawi

3.1 Genes, 3.2 chromosomes Define the following terms. Genome: Is all the genetic information of an organism. - In humans: it is the 46 chromosomes plus the mitochondrial DNA. - In plants: DNA in nucleus plus DNA in mitochondria and chloroplasts - In prokaryotes: DNA in circular chromosome plus DNA in plasmids. Gene: heritable factor that consists of a length of DNA and influences a specific characteristic. Gene locus: the specific location of a gene on a chromosome. Allele: one specific form of a gene, differing from other alleles by one or a few bases only and occupying the same gene locus as other alleles of the gene, new alleles can be formed by mutations. -

The different alleles of a gene have slight variations in the base sequence. Usually only one or a very small number of bases are different. For example, adenine might be present at a particular position in the sequence in one allele and cytosine at that position in another allele. Positions in a gene where more than one base may be present are called single nucleotide polymorphisms, abbreviated to SNPs and pronounced snips. Several snips can be present in a gene, but even then the alleles of the gene differ by only a few bases.

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Unit 3:Genetics

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Rana Al Liddawi

Compare and contrast the number of genes found in humans with other organisms.

Genome sequencing has allowed the number of genes from a number of species to be estimated. Comparisons:  Prokaryotes have less genes than eukaryotes.  Some other animals have fewer genes than humans but some have more.  Animals have more genes than fungi.  A fruit fly only has slightly less genes than a human.  Flowering plants, though less complex, have more genes than humans.  The trend that more complex organisms have more genes is weak.

What is a gene mutation? Gene mutation: a change to the base sequence of a gene. - Mutation rate can be increased by exposure to mutagens. - Mutations lead to the creation of new alleles. - Thus mutations create genetic variation. - Mutations can be neutral(most), harmful (some) and beneficial (very few).

Explain the consequence of a base substitution mutation in relation to the processes of transcription and translation, using the example of sickle-cell anemia.(describe the cause of sickle cell anemia). Sickle cell anaemia is a genetic disease that affects red blood cells in the body. Cause:  

Caused by a mutation (base mutation) on the Hb gene which codes for the beta polypeptide which is part of haemoglobin. Hemoglobin consists of 4 polypeptide chains:2 alpha and 2 Beta chains.

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Unit 3:Genetics

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Rana Al Liddawi



This changes the code on the DNA as follows: GAG (on sense strand) found in the normal Hb gene is mutated to GTG. This is called a base substitution mutation as adenine (A) is replaced by thymine (T).

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This leads to a change in transcription and mRNA produced: instead of the normal codon GAG, the mRNA will contain the codon GUG.

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This in turn will result in a mistake during translation: In a healthy individual the codon GAG on the mRNA matches with the anticodon CUC on the tRNA carrying the amino acid glutamic acid. However, if the mutated gene is present then GUG on the mRNA matches with the anticodon CAC on the tRNA which carries the amino acid valine. So the base substitution mutation has caused glutamic acid to be replaced by valine on the 6th position on the polypeptide.

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This results in the formation of the abnormal haemoglobin (S) in red blood cells instead of the normal haemoglobin A.

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This has an effect on the phenotype as instead of normal donut shaped red blood cells being produced some of the red blood cells will be sickle shaped which causes anemia.

Consequences:    

Sickle shaped red blood cells cannot carry oxygen as efficiently as normal red blood cells would. Symptoms may include fatigue and shortness of breath. The sickle hemoglobin causes the red blood cells to become less flexible and may get stuck in the small blood capillaries causing pain. Homozygote (HBSHBS) has lethal sickle cell anemia whereas heterozygote (HBSHBA) carry the trait and half of the red blood cells would be sickled. Heterozygotes are more resistant to malaria.

Malaria and sickle cell anemia: The sickle cell red blood cells give resistance to malaria and so the allele Hbs on the Hb gene which causes sickle cell anemia is quite common in parts of the world where malaria is found as it provides an advantage over the disease. There has clearly been natural selection in favor of the sickle-cell allele in malarial areas, despite it causing severe anemia in the homozygous condition. Natural selection has led to particular frequencies of the sickle-cell and the normal hemoglobin alleles, to balance the twin risks of anemia and malaria.

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Unit 3:Genetics

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Rana Al Liddawi

Summary of important steps: Normal Hb Gene

Mutated Hb gene

DNA triplet (sense strand)

GAG

GTG

DNA triplet(antisense strand)

CTC

CAC

mRNA codon

GAG

GUC

Anticodon CUC and amino acid glutamic acid on tRNA.

Anticodon CAC and amino acid valine on tRNA.

HbA

HbS

Phenotype

Normal donut shaped red blood cells.

Sickle cell shaped red blood cells.

Effects

Carry oxygen efficiently but are affected by malaria.

Do not carry oxygen efficiently but give resistance to malaria.

Translation (sixth amino acid in polypeptide) Haemoglobin

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Unit 3:Genetics

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Rana Al Liddawi

Outline the Human Genome Project       

The order of base pairs in DNA fragments can be determine by a technique called DNA sequencing. Improvements in sequencing technology allowed more DNA sequence to be determined faster and cheaper. Bioinformatics software was also developed to join Overlapping fragments of DNA sequence together. An ambitious project to sequence the entire human genome was started in the 1990's. The project included collaboration between scientists from several countries and it was completed in 2003. The human genome comprises about 3.2 billion base pairs(23000 genes). Further improvements in sequencing speed and reduced costs, have enabled the genomes of thousands of other organisms to be sequenced.

Outline some of the outcomes of the sequencing of the human genome. 1. knowledge of location of human genes / position of human genes on chromosomes; 2. knowledge of number of genes/interaction of genes / understanding the mechanism of mutations; 3. evolutionary relationships between humans and other animals; 4. discovery of proteins / understanding protein function / detection of genetic disease; 5. leads to the development of medical treatment/enhanced research techniques; 6. knowledge of the base sequence of genes/study of variation within genome; 7. Most of the genome is not transcribed. Originally called "junk DNA,” it is being increasingly recognized that within these "junk" regions, there are elements that affect gene expression as well as highly repetitive sequences, called satellite DNA.

How can the base sequence of the same gene in two species be compared?   

Changes in the base sequence of genes occur over time. If a species splits to form two separate species, differences between the base sequences of the genes of those two species will gradually accumulate. The number of differences can give an indication of how long ago species diverged from the common ancestral species.

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Unit 3:Genetics  

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Rana Al Liddawi

It is therefore useful to be able to compare the base sequences of genes and find out how many differences there are. This can be done using base sequence data from the GenBank database and downloadable software.

How? 1. The GenBank database is used to obtain the base sequence of a gene from any organism that has been sequenced. 2. BLAST (Basic Local Alignment Search Tool) analysis is used to compare the gene to all other known sequences. 3. This allows the comparison of the same gene between two (or more) species to observe genetic variation. 4. One suitable gene for comparison is cytochrome C. It is present in all eukaryotes and codes for a key protein involved in aerobic respiration. Similar sequences are found in the other domains of life (bacteria and archaea). 5. Sequence variations can be used to determine evolutionary relationships between two species (this is called cladistics). 6. Regions of a sequence that do not vary (conserved sequences), may indicate amino acids essential for protein function.

3.2 Chromosomes Distinguish chromosomes in prokaryotes and eukaryotes. Prokaryotes chromosomes Naked DNA circular One chromosome Free in the cytoplasm Plasmids may be present No introns Does not Contain highly repetitive DNA sequences

Eukaryotes chromosomes DNA associated with histone proteins Linear At least one chromosome Contained in nucleus No plasmids Introns present Contain highly repetitive DNA sequences

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Unit 3:Genetics

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Rana Al Liddawi

Outline Cairn’s technique for measuring the length of DNA molecules and what has been discovered from its use.

1. Cairns' technique uses autoradiography and electron microscopy to allow visualization of chromosomes. 2. Autoradiography involves radioactively labeling a substance, which can then be visualized using photographic film. 3. E. coli were grown in a medium containing radioactively labeled thymine ( tritiated thymidine (H3-TdR) , H3 is heavy isotope of hydrogen and it replaces normal hydrogen in thymidine to give rise to tritiated thymidine. 4. This ensures only DNA will become radioactive. 5. E. coli cells were ruptured on a membrane. 6. Photographic film was placed over the membrane (for 2-3 months) 7. After the film was developed, the chromosomes could be Seen. 8. Cairns discovered that bacterial chromosomes were circular and approximately 1 mm long (even though an E. coli cell is only about 2 Mm long). 9. Other scientists using the same technique found eukaryotes had very long, linear chromosomes (up to 12 mm long in Drosophila).

pearson

Describe the function of histones in eukaryotic chromosomes.

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Histones help organize the DNA and enable chromosomes to coil This enables very long, linear chromosome to fit inside the nucleus. In their most relaxed form, chromosomes resemble beads on a string. 7

Unit 3:Genetics    

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Rana Al Liddawi

DNA (string) is wrapped around histones (beads) During mitosis, the chromosomes supercoil. They are at their most condensed at metaphase. chromosomes can be seen with a light microscope and are made up of two sister chromatids joined at the centromere.

What are plasmids and which organisms contain them?  

Plasmids are present in most prokaryotes. They are small loops of naked DNA.

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Plasmids can be passed from one bacteria to another via pili. This is how antibiotic resistance genes spread in bacterial populations. Eukaryotes do not have plasmids.

Compare genome size in the following organisms. Organism T2 phage

Genome size(billions of base pairs) 0.18

Escherichia coli

4.6

Drosophila melanogaster (fruit fly)

130

Homo sapiens (human)

3,200

Paris japonica (Japanese canopy plant)

150,000

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Genomes of different species vary greatly in size. Species with larger genomes typically have more chromosomes. Generally, there is an increase in genome size with organism complexity. Many plants have very large genomes due to chromosome doubling events (polyploidy).

Fact: Paris japonica has the largest genome of all organisms studied.

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Unit 3:Genetics

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Rana Al Liddawi

Distinguish between haploid and diploid nuclei. Cells with a diploid nucleus:  The majority of eukaryotic organisms are mostly comprised of cells with a diploid nucleus.  These are also known as body or somatic cells.  In humans, a diploid nucleus contains 46 chromosomes.  Thus, there are 23 pairs of different chromosomes.  The chromosomes in each pair contain the same genes in the same order but they may have different alleles of each gene.  They are called homologous chromosomes.  A diploid nucleus has pairs of homologous chromosomes. Cells with a haploid nucleus:  An example of a cell with a haploid nucleus is a gamete, such as a sperm cell.  A haploid nucleus only contains one chromosome of each homologous pair.  human sperm contains 23 different chromosomes.

Define terms karyotype and karyogram. How are chromosomes arranged in karyogram? Karyotype: the number of different chromosomes present in cell. Karyogram: is a photograph of the karyotype.

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Karyograms show the different chromosomes arranged in homologous pairs according to their: a. size b. banding pattern c. centromere position Metaphase chromosomes are used. Chromosome 1 is the longest and 22 is the shortest. X and Y are the sex chromosomes. 9

Unit 3:Genetics

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Rana Al Liddawi

Outline the uses of karyograms. Karyograms are used to determine sex or to diagnose conditions caused by chromosomes abnormalities. 1. Sex:  The sex chromosome determines the gender of the individual.  There is normally one pair of sex chromosomes.  XY is male.  XX is female.  The other 22 chromosomes are called autosomes.  They do not determine sex. 2. Chromosome abnormalities:  Chromosomes should be present in pairs.  For example, an extra chromosome 21 indicated Down’s syndrome.

Use the karyograms to detrmine the sex and diagnose any chromosomal abnormalities in the two individuals.

Normal male

Female with Down’s syndrom

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Unit 3:Genetics

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Rana Al Liddawi

Compare the number of diploid chromosomes in the following species.

Number of diploid chromosomes Species Homo sapiens (human) Pan troglodytes (chimpanzee) Canis familiaris (dog) Oryza sativa (rice) Paracaris equorum (horse threadworm)

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Number of diploid chromosomes 46 48 78 24 4

Karyograms can be used to study the number of chromosomes from different species. There is great variation in the chromosome number between species. Each different species has a characteristic number of chromosomes. Within a species, all individuals have the same number of chromosomes.

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Unit 3:Genetics

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Rana Al Liddawi

Nature of Science: Different methods of DNA sequencing are used to work out either the sequence of individual genes, groups of genes or even entire chromosomes and genomes.  Some processes involve: 1. Cutting DNA into short segments using restriction enzymes. 2. Each one is sequenced separately. 3. To find the base sequence of a DNA fragment, single stranded copies are made by using DNA polymerase(PCR) but the process will be stopped before the whole sequence has been copied by using (di-deoxyribonucleotides, 4 types) 4. Four samples of DNA strands will be produced, each has a different length and a has one of the four bases at the end of the strand. 5. The four samples will be separated by gel electrophoresis according to length. 6. For each number of nucleotides in the copy there is a band in just one of the four tracks in the gel, from which the sequence of bases in the DNA can be deduced.

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The major advance in technology that speeded up base sequencing by automating it is this:     

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Colored fluorescent markers are used to mark the DNA copies. A different color of fluorescent marker is used for the copies ending in each of the four bases. The samples are mixed together and all the DNA copies are separated in one lane of a gel according to the number of nucleotides. A laser scans along the lane to make the fluorescent markers fluoresce. An optical detector is used to detect the colors of fluorescence along the lane. There is a series of peaks of fluorescence, corresponding to each number of nucleotides A computer deduces the base sequence from the sequence of colors of fluorescence detected.

Databases have also been invaluable in genome research and are used for storing long sequences about proteins. Examples of online databases:

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Unit 3:Genetics

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Rana Al Liddawi

Essential idea: Every living organism inherits a blueprint for life from its parents. 3.1 Genes Nature of science: Developments in scientific research follow improvements in technology – gene sequencers are used for the sequencing of genes. Understandings:

International-mindedness:

A gene is a heritable factor that consists of a length of DNA and influences a specific characteristic.

Sequencing of the human genome shows that all humans share the vast majority of their base sequences but also that there are many single nucleotide polymorphisms that contribute to human diversity. (pp. 136-137)

A gene occupies a specific position on a chromosome. The various specific forms of a gene are alleles. Alleles differ from each other by one or only a few bases. New alleles are formed by mutation. The genome is the whole of the genetic information of an organism. The entire base sequence of human genes was sequenced in the Human Genome Project. Applications and skills: Application: The causes of sickle cell anaemia, including a base substitution mutation, a change to the base sequence of mRNA transcribed from it and a change to the sequence of a polypeptide in haemoglobin. (pp.)

Theory of knowledge: There is a link between sickle cell anaemia and the prevalence of malaria. How can we know whether there is a causal link in such cases or simply a correlation? Aims: Aim 7: The use of a database to compare DNA base sequences. Aim 8: Ethics of patenting human genes.

Application: Comparison of the number of genes in humans with other species. (pp.) Skill: Use of a database to determine differences in the base sequence of a gene in two species. (pp.) Guidance: Students should be able to recall one specific base substitution that causes glutamic acid to be substituted by valine as the sixth amino acid in the haemoglobin polypeptide. (pp.) The number of genes in a species should not be referred to as genome size as this term is used for the total amount of DNA. At least one plant and one bacterium should be included in the comparison and at least one species with more genes and one with fewer genes than a human. ((pp. 137-138) The Genbank® database can be used to search for DNA base sequences. The cytochrome C gene sequence is available for many different organisms and is of particular interest because of its use in reclassifying organisms into three domains. (pp.) Deletions, insertions and frame shift mutations do not need to be included. (p.)

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Unit 3:Genetics

core

Rana Al Liddawi

Essential idea: Chromosomes carry genes in a linear sequence that is shared by members of a species. 3.2 Chromosome...