PowerPoint Presentation

Gene Expression, DNA Mutations, and Cancer

Chromosome TheoryChromosomal theory of inheritanceStates genes are located on chromosomes and that the behavior of chromosomes during meiosis accounts for inheritance patterns, which closely parallels predicted Mendelian patterns.Principles of Mendelian genetics (segregation, independent assortment, and dominance) support chromosomal theory of inheritance2Chromosome TheoryChromosomal theory of inheritancedeveloped in 1902 by Walter Suttonproposed that genes are present on chromosomesbased on observations that homologous chromosomes pair with each other during meiosissupporting evidence was provided by work with fruit flies3New Developments Since Mendels principles of genetics41. Gene LinkageGene Linkage genes that are located on the same chromosome will be inherited togetherThis is the exception to the Mendelian principle of independent assortment because linked genes do not separate independentlyLets look at the following example of fruit flies Drosophila Melanogaster 5On the left is the expected phenotypic ratio of the offspring from a BbVv bbvv cross (1:1:1:1). However, because the alleles BV and bv are linked, the observed phenotypic ratio is much different (5:1:1:5) than the expected ratio.6

ReasoningWhat are the genotypes of BbVv parents?BBVV X bbvv p generationSo what do the parents always donate to their offspring on each chromosomeOne parent donates chromosome with BVOne parent donates chromosome with bvTherefore the offspring BbVv is going to produce many more BV or bv since the genes are linked72. Crossing OverCrossing over alleles in close proximity on homologous chromosomes are exchanged new combinations of allelesIn meiosis I segments of chromosomes entwine and exchange infoCrossing over allows for greater genetic diversity8

3. Incomplete Dominance and Codominance9

4. Multiple Alleles andPolygenic TraitsMultiple alleles can exist for a particular trait even though only 2 alleles are inherited. Ex 3 alleles exist for blood type (A,B, and O) which results in 4 different blood groups10

4. Multiple Alleles andPolygenic TraitsPolygenic traits traits that are controlled by 2 or more genes. These traits show a great variety of phenotypes. ie skin color, hair color, eye color, height11

5. Sex-Linked TraitsSex-Linked traits are the result of genes that are carried on either the X or the Y chromosome.It is another exception to the Law of Independent Assortment125. Sex-Linked TraitsT.H. Morgan isolated a mutant white-eyed Drosophilared-eyed female X white-eyed male gave a F1 generation of all red eyesMorgan concluded that red eyes are dominant135. Sex-Linked TraitsMorgan crossed F1 females X F1 males (so all had red eyes)F2 generation contained red and white- eyed flies but all white-eyed flies were maletestcross of a F1 female with a white-eyed male showed the viability of white-eyed femalesMorgan concluded that the eye color gene is linked to the X chromosome14Chromosomal basis of sex linkage

White-eyed male flies X red-eyed femalesF1 flies all have red eyesF2 flies, all of the white-eyed flies are males because the Y chromosome lacks the white gene15

Sex ChromosomesSex determination in Drosophila is based on the number of X chromosomes2 X chromosomes = female1 X and 1 Y chromosome = male

Sex determination in humans is based on the presence of a Y chromosome2 X chromosomes = femalehaving a Y chromosome (XY) = male16Sex ChromosomesIn many organisms, the Y chromosome is greatly reduced or inactive.genes on the X chromosome are present in only 1 copy in malessex-linked traits: controlled by genes present on the X chromosomeHuman X-linked disordersColor blindness, Muscular dystrophy, Hemophilia, Fragile X syndromeSex-linked traits show inheritance patterns different than those of genes on autosomes.17Royal Hemophilia Pedigree18

Chromosome Theory ExceptionsMitochondria and chloroplasts contain genes.traits controlled by these genes do not follow the chromosomal theory of inheritancegenes from mitochondria and chloroplasts are often passed to the offspring by only one parent19Chromosome Theory ExceptionsMaternal inheritance: uniparental (one-parent) inheritance from the motherthe mitochondria in a zygote are from the egg cell; no mitochondria come from the sperm during fertilizationin plants, the chloroplasts are often inherited from the mother, although this is species dependent20Human Genetic DisordersSome human genetic disorders are caused by altered proteins.the altered protein is encoded by a mutated DNA sequencethe altered protein does not function correctly, causing a change to the phenotypethe protein can be altered at only a single amino acid (e.g. sickle cell anemia)21Sickle-Cell Anemia22

Human Genetic DisordersSome genetic disorders are caused by a change in the number of chromosomes.nondisjunction during meiosis can create gametes having one too many or one too few chromosomesfertilization of these gametes creates trisomic or monosomic individualsDown syndrome is trisomy of chromosome 2123Down Syndrome24

Human Genetic DisordersNondisjunction of sex chromosomes can result in:

25SyndromeSexDisorderChromosome #Spontaneous abortionsLive births

TurnerFXO451/181/ 2,500KlinefelterMXXY OR XXXY47 or 481/3001/800Poly-XFXXX OR XXXX47 or 4801/ 1,500JacobsMXYY47?1/1,000DownM or FTrisomy 21471/401/800Abnormalities in the # of sex chromosomes26

Human Genetic DisordersGenetic counseling can use pedigree analysis to determine the probability of genetic disorders in the offspring.Some genetic disorders can be diagnosed during pregnancy.amniocentesis collects fetal cells from the amniotic fluid for examinationchorionic villi sampling collects cells from the placenta for examination27Amniocentesis28

Chorionic villi sampling29

DNA Mutations30MutationsA mutation is the alteration of an organisms DNA. Mutations can range from a change in one base pair to the insertion or deletion of large segments of DNA. Mutations can result from a malfunction during the process of meiosis or from exposure to a physical or a chemical agent, a mutagen.

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Mutation on the gene that produces myostatin, a protein that blocks skeletal muscle growthMutationsMost mutations are automatically repaired by the organisms enzymes and therefore have no effect. However, when the mutation is not repaired, the resulting altered chromosome or gene structure is then passed to all subsequent daughter cells of the mutant cell, which may have adverse or beneficial effects on the cell, the organism, and future generations.

32Mutationshappens randomly every few thousand cell divisionscan be increased by exposure tomutagenslike chemicals or radiationcan be in somatic cells or in germ cells (gametes)can be POSITIVE, NEGATIVE, or NEUTRAL(silent)are the "raw material" for evolution bynatural selection

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Video ClipMutations"Point mutation"can be caused by single nucleotide substitution.Affects only one of the amino acids in the protein.Video Clip

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MutationsInsertionsordeletionsof nucleotide bases can cause even more serious problems:called a "Frameshiftmutation" :insertion or deletion of a single base can throw off "reading frame" for amino acid coding. This most often renders the (coded) proteinnonfunctional.35

CancerCancer is one of the most common diseases in the developed world:1 in 4 deaths are due to cancer1 in 17 deaths are due to lung cancerLung cancer is the most common cancer in menBreast cancer is the most common cancer in womenThere are over 100 different forms of cancer36Normal CellsCells can respond to physical signals from their environmentCells sense when they are too closely packed and cell division is turned off Cells sense when they are not in contact with a surface and cell division is turned onThere are checkpoints along the cell life cycle where these decisions are made based on stimuli37CancerCancer cells are examples of cells that dont recognize normal off signals or there is no growth factor so they continue to divide Cancerous cells divide repeatedly out of control even though they are not needed, they crowd out other normal cells and function abnormally. They can also destroy the correct functioning of major organs.38CancerNormally the bodys immune system will recognize that the cell is damaged and destroy it

39What causes cancer?Cancer arises from the mutation of a normal gene.Mutated genes that cause cancer are called oncogenes.It is thought that several mutations need to occur to give rise to cancerCells that are old or not functioning properly normally self destruct and are replaced by new cells.However, cancerous cells do not self destruct and continue to divide rapidly producing millions of new cancerous cells.40A factor which brings about a mutation is called a mutagen.

A mutagen is mutagenic.

Any agent that causes cancer is called a carcinogen and is described as carcinogenic.

So some mutagens are carcinogenic.41CarcinogensIonising radiation X Rays, UV light

Chemicals tar from cigarettes

Virus infection papilloma virus can be responsible for cervical cancer.

Hereditary predisposition Some families are more susceptible to getting certain cancers. Remember you cant inherit cancer its just that you maybe more susceptible to getting it.42Benign or malignant?Benign tumours do not spread from their site of origin, but can crowd out (squash) surrounding cells eg brain tumour, warts.

Malignant tumours can spread from the original site and cause secondary tumours. This is called metastasis. They interfere with neighbouring cells and can block blood vessels, the gut, glands, lungs etc.

Why are secondary tumours so bad?

Both types of tumour can tire the body out as they both need a huge amount of nutrients to sustain the rapid growth and division of the cells.43Metastasis Video ClipWhat makes most tumours so lethal is their ability to metastasize -- that is, establish new tumour sites at other locations throughout the body.