3 Key ConceptsHow is sex determined?How do small changes in DNA cause genetic disorders?
4 How do biologists go about studying human DNA? They use something called a KARYOTYPEBiologists photograph cells in mitosis, when chromosomes are easier to see. They cut out the chromosomes from the photographs and group them together in pairs
5 Humans have a total of 46 chromosomes – half (23) from mom and half (23) from dad Out of those 46, two are called SEX CHROMOSOMESDetermine an individual’s sexFemales have two copies ofa larger X chromosomeMales have one large Xand a smaller Y chromosome
6 AUTOSOMESThe other 44 chromosomesFemales – 46XXMales - 46XY
7 How is the X chromosome different from the Y chromosome? Look at the karyotype in your notes, is this individual male or female?MaleHow is the X chromosome different from the Y chromosome?The X chromosome is longer
8 All egg cells carry a single X chromosome. How is sex determined?All egg cells carry a single X chromosome.However, half of all sperm cells carry an X chromosome.This ensures that about half of the zygotes will be 46XX and half will be 46XY
9 Finish this Punnett Square to see how sex is determined Y
11 How do biologists identify an inherited trait that is controlled by a single gene? They must establish that the trait is actually inherited and not a result of environmental influences-They have to study how the trait is passed from one generation to the next
12 Shows the relationship within a family; helps to study genetic traits PEDIGREEShows the relationship within a family; helps to study genetic traitsCan help parents understand the probability of having a child with a genetic disorder
13 Figure 14-3 A Pedigree Go to Section: A circle represents a female. A square represents a male.A horizontal line connecting a male and female represents a marriage.A vertical line and a bracket connect the parents to their children.A half-shaded circle or square indicates that a person is a carrier of the trait.A circle or square that is not shaded indicates that a person neither expresses the trait nor is a carrier of the trait.A completely shaded circle or square indicates that a person expresses the trait.Go to Section:
14 What do circles represent? -FemalesWhat do squares represent?-MalesWhat does a horizontal line represent?Between a male and female represents a marriageWhat does a vertical line represent?Connects parent to their children
15 What does a circle or square that is not shaded represent? -That person does not express a trait nor are they a carrierWhat does a fully shaded circle or square represent?-The person expresses a trait
16 What does a half shaded circle or square represent? The person is a carrier of the traitWhat is the sex of the last person in the second row? Does that person have the trait?Female; no
17 Pedigree analysis reveals Mendelian patterns in human inheritance data mapped on a family tree= male= female= male w/ trait= female w/ trait
18 POLYGENICA trait controlled by many genesHow can you find out where you get your good looks from?This is actually rather difficultMany traits are polygenic like the shape of your eyes or earsMany of your traits are only partly governed by genetics – environmental influences (nutrition, exercise) can affect how a trait is expressed
19 What is your blood type?Why is it important for a doctor to know your blood type before they give you a blood transfusion?Using the wrong blood type during a transfusion can be fatal
20 The best known blood groups are ABO and Rh -Rh blood group is determined by a single gene with two alleles –positive and negative-Rh stands for rhesus monkey – this was the first animal where they discovered this factor
21 The positive allele is dominant –If you are Rh+/Rh+ or Rh+/Rh- you are considered Rh positiveThe negative allele is recessiveIf you have two Rh- alleles you areRh negative
22 ABO a little more complicated There are three alleles IA, IB, and I Alleles IA and IB are codominantThese alleles produce molecules known as antigens that your immune system can recognize on the surface of red blood cellsIf you have IAIA you only produce A antigens etc. – see fig 14-4 p. 344
23 Figure 14-4 Blood Groups Go to Section: Safe Transfusions Phenotype (Blood TypeAntigen onRed Blood CellGenotypeToFromGo to Section:
24 If you are homozygous ii you have no antigen on your red blood cells this is blood type O Typically nurses and doctors will use both blood types like AB negative or O positive
25 What happens if you give type A blood to a type O patient? The immune system will recognize the blood cells as foreign (they don’t belong) because of the A antigens on the cell’s surfaces. The immune system will produce antibodies against these blood cells and destroy them
26 Why are type AB people called universal acceptors? They can accept any blood typeWhy are type O called universal donors?They can donate to any blood typeWhat blood type do you think most blood banks want to have on hand?Type O because is has no antigens and can be given to any blood type without causing an antibody reaction
27 If a woman with type O blood and a man with type AB blood have children, what are the children’s possible phenotypes?Use a Punnett Square to answer
29 Genotypes: IAi and IBi Phenotypes: Type A and Type B
30 Genetic Disorders-they are disorders that are inherited in our genes AutosomolDisorderscaused byRecessive allelesDominant allelesCodominant allelesincludeincludeincludeAlbinismGalactosemiaTay-Sachs diseaseHuntington’s diseaseSickle cell diseaseCystic fibrosisPhenylketonuriaAchondroplasiaHypercholes-terolemiaGo to Section:
31 If there is a known genetic condition a doctor may suggest a couple go through genetic counseling to determine their risk of having a child with an inherited genetic condition.A pedigree can help us understand the past & predict the futureThousands of genetic disorders are inherited as simple recessive traitsbenign conditions to deadly diseasesalbinismcystic fibrosisTay sachssickle cell anemiaPKU
32 Genetic testing - may be done to determine if an unborn child has a genetic disorder. Example: Amniocentesis
33 Recessive diseasesThe diseases are recessive because the allele codes for either a malfunctioning protein or no protein at allHeterozygotes (Aa)carriershave a normal phenotype because one “normal” allele produces enough of the required protein
34 Aa A a A a AA Aa A a AA Aa Aa A a Aa aa Aa aa Heterozygote crossesHeterozygotes as carriers of recessive allelesAa x AaAaAaAamale / spermAAAaAafemale / eggsAAAaAaAaAaaaAaaa
36 Phenylketonuria – PKUPeople lack an enzyme to break down phenylalaninePhenylalanine is an amino acid found in milk and many other foodsIf a child with PKU eats phenylalanine and it builds up in their tissues – mental retardation occursThere is a testTreatment – the person must be on a low-phenylalanine diet their entire lifeCaused by a recessive allele on chromosome 12
37 Tay-Sachs strikes 1 in 3600 births Primarily Jews of eastern European (Ashkenazi) descent & Cajunsstrikes 1 in 3600 births100 times greater than incidence among non-Jews or Mediterranean (Sephardic) Jewsnon-functional enzyme fails to breakdown lipids in brain cellssymptoms begin few months after birthseizures, blindness & degeneration of motor & mental performancechild dies before 5yo
38 Tay-Sachs disease (continued) Caused by an allele found in Jewish families with central and eastern European ancestryResults in nervous system breakdown and death in the first few years of lifeThere is no treatmentParents can be tested ahead of time to see if they are carriers
39 Dominant allele disorders AchondroplasiaOne type of dwarfismThe person never reaches a height greater than 4 feet 4 inches tallArms and legs form disproportionately short1 in about 10,000 people are affected
40 Huntington’s diseaseCauses progressive loss of muscle control and mental function until death occursSymptoms don’t show until people are in their thirties and forties
41 Codominant allele disorders Sickle cell anemiaPrimarily Africansstrikes 1 out of 400 African Americanscaused by substitution of a single amino acid in hemoglobinwhen oxygen levels are low, sickle-cell hemoglobin crystallizes into long rodsDue to this shape the cells are more rigid and they tend to get stuck in capillaries causing blockagesCauses physical weakness, brain damage, damage to the heart and spleendeforms red blood cells into sickle shapesickling creates pleiotropic effects = cascade of other symptoms
42 Doctors can use regular blood transfusions to prevent brain damage and new drugs to prevent or treat other problems.
43 2 alleles are codominant Sickle cell phenotype2 alleles are codominantboth normal & abnormal hemoglobins are synthesized in heterozygote (Aa)carriers usually healthy, although some suffer some symptoms of sickle-cell disease under blood oxygen stressexercise
44 Heterozygous people still have sickle shaped red blood cells but not as many When the body destroys sickled cells, it gets rid of the Malaria parasite at the same timeIn regions where Malaria is a problem, it is beneficial for people to be heterozygous for sickle cell disease
45 Heterozygote advantage Malariasingle-celled eukaryote parasite spends part of its life cycle in red blood cellsHeterozygous people still have sickle shaped red blood cells but not as manyWhen the body destroys sickled cells, it gets rid of the Malaria parasite at the same timeIn regions where Malaria is a problem, it is beneficial for people to be heterozygous for sickle cell diseaseIn tropical Africa, where malaria is common:homozygous normal individuals die of malariahomozygous recessive individuals die of sickle cell anemiaheterozygote carriers are relatively free of both
46 Malaria, a serious parasitic disease that infects red blood cells, is common in certain regions of Africa. People who are heterozygous for sickle cell disease are generally healthy and they are resistant to Malaria
47 Prevalence of MalariaHigh frequency of sickle cell allele in African Americans is vestige of African rootsPrevalence of Sickle Cell Anemia
48 Cystic FibrosisCommon in people whose ancestors come from Northern Europestrikes 1 in 2500 births1 in 25 whites is a carrier (Aa)Recessive allele on chromosome number 7 the normal allele codes for a membrane protein that transports Cl- across cell membranedefective or absent protein channels cause high extracellular levels of Cl-thicker & stickier mucus coats around cellsmucus build-up in the pancreas, lungs, digestive tract & causes bacterial infectionsChildren with CF have serious digestive problemsThey produce thick, heavy mucous that clogs their lungs and breathing passagesWithout treatment children die before 5; with treatment can live past their late 20s
49 mucus secreting glands Normal LungsChloride channelTransports chloride through protein channel out of cell.Osmotic effects: H2O follows Cl-Cl-airwayNa+cells lining lungsIn people without cystic fibrosis, working cystic fibrosis proteins allow salt (chloride) to enter the air space and water follows by osmosis. The mucus layer is dilute and not very sticky.mucus secreting glands
50 bacteria & mucus build up thickened mucus hard to secrete Cystic fibrosisdamaged lung tissueCl-airwayNa+bacteria & mucus build upcells lining lungsIn people with cystic fibrosis, non-working cystic fibrosis proteins mean no salt (chloride) enters the air space and water doesn't either. The mucus layer is concentrated and very sticky.People with cystic fibrosis have lung problems because:Proteins for diffusion of salt into the airways don't work. (less diffusion)Less salt in the airways means less water in the airways. (less osmosis)Less water in the airways means mucus layer is very sticky (viscous).Sticky mucus cannot be easily moved to clear particles from the lungs.Sticky mucus traps bacteria and causes more lung infections.Therefore, because of less diffusion of salt and less osmosis of water, people with cystic fibrosis have too much sticky mucus in the airways of their lungs and get lots of lung infections. Thus, they are sick a lot.thickened mucus hard to secrete
54 Key ConceptsWhy are sex linked disorders more common in males, than in females?What is nondisjunction, and what problems does it cause?
55 Look at page 341. Which chromosomes are the largest? 1 and 2 Which chromosomes are the smallest?18-22Considering the chromosome sizes, how many bases might chromosome 1 have if chromosome 22 has about 43 million bases?About three times as many – 129 million
56 Chromosome 21 and 22 are the smallest human autosomes These were the first two chromosomes whose sequences were discoveredChromosome 22 has 545 genesProblems with this chromosomegenetic disorders are: an allele associated with a form of leukemia and another associated with neurofibromatosis (a tumor-causing disease of the nervous system)
57 Chromosome 21 has 225 genesGenetic disorders are: amyotrophic lateral sclerosis (ALS) also known as Lou Gehrigs diseasethis disease causes a progressive loss of muscle control due to the destruction of nerves in the brain and spinal cord
58 Recall:Genes located on the same chromosome are linked, meaning they tend to be inherited togetherGenes may be separated by recombination (during crossing-over) in meiosis
59 Look at p. 350 fig 14-12Which chromosome carries more genes?The X chromosomeSEX-LINKED GENESA gene located on the X or Y chromosome
60 More than 100 sex-linked genetic disorders have been mapped to the X chromosome The Y chromosome is much smaller and appears to only carry a few genes
61 Why are sex-linked disorders more common in males than in females? Males have just one X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive.
62 Colorblindness the person cannot see certain colors the human genes associated with colorblindness are located on the X chromosomein males, a defective version of any one of these genes produces colorblindnessred-green colorblindness (cannot see green) found in 1 out of 10 males in US but only 1 in 100 females
67 She is heterozygous and is a carrier Why is the circle for the mother shaded only halfway?She is heterozygous and is a carrierWould you expect the colorblind son to have sons who are colorblind?No, the son can only pass the Y chromosome to his sonsWhat is the probability that the daughter who is a carrier will have a colorblind child if she marries a man with normal vision?25%
68 Hemophilia A protein necessary for normal blood clotting is missing Two important genes carried on the X chromosome help control blood clotting – a recessive allele in either of these two genes may produce the disorder1 in 10,000 males are born with itPeople with hemophilia can bleed to death from a minor cut or could suffer internal bleeding from bumps or bruisesThese people are treated with injections of clotting proteins
69 Duchenne Muscular Dystrophy Results in the progressive weakening and loss of skeletal musclePeople rarely live past adulthood1 in 3000 males is born with it
70 Calico cats Females have two X chromosomes, but males only have one If just one X chromosome is enough for cells in males, how does the cell adjust to the extra X chromosome in female cells?Scientists have found that in female cells, one X chromosome is randomly switched off
71 A gene that controls coat color is located on the X chromosome One X chromosome may have an allele for orange spots and the other may have an allele for black spots.In some cells on the cat’s body one X chromosome (orange spots) is switched on while the other X chromosome in those cells is switched off
72 Then in other areas the opposite occurs – the black spots X chromosome switches on and the other switches offMale cats have only one X chromosome so they can only have spots of one color
73 The turned off chromosome forms a dense region in the nucleus known as a Barr Body Barr bodies are not found in males because their X is always turned onWhat is the sex of the cat in fig ?Female
74 Chromosomal abnormalities Incorrect number of chromosomesnondisjunctionchromosomes don’t separate properly during meiosisbreakage of chromosomesdeletionduplicationinversiontranslocation
75 NondisjunctionProblems with meiotic spindle cause errors in daughter cellstetrad chromosomes do not separate properly during Meiosis 1sister chromatids fail to separate during Meiosis 2too many or too few chromosomes2nn-1n+1n
77 Baby has wrong chromosome number trisomy monosomy NondisjunctionBaby has wrong chromosome numbertrisomycells have 3 copies of a chromosomemonosomycells have only 1 copy of a chromosomemonosomy2n-1trisomy2n+1
78 Human chromosome disorders High frequency in humansmost embryos are spontaneously abortedalterations are too disastrousdevelopmental problems result from biochemical imbalanceCertain conditions are toleratedupset the balance less = survivecharacteristic set of symptoms = syndrome
79 Down syndrome Trisomy 21 3 copies of chromosome 21 1 in 700 children born in U.S.Chromosome 21 is the smallest human chromosomebut still severe effectsFrequency of Down syndrome correlates with the age of the mother
81 Down syndrome & age of mother Mother’s ageIncidence of Down SyndromeUnder 30<1 in 1000301 in 900351 in 400361 in 300371 in 230381 in 180391 in 135401 in 105421 in 60441 in 35461 in 20481 in 16491 in 12
82 Genetic testing Amniocentesis in 2nd trimester sample of embryo cells stain & photograph chromosomesAnalysis of karyotype
83 Sex chromosomesHuman development more tolerant of wrong numbers in sex chromosomeBut produces a variety of distinct conditions in humansXXY = Klinefelter’s syndrome maleXXX = Trisomy X femaleXYY = Jacob’s syndrome maleXO = Turner syndrome female
84 Klinefelter’s syndrome XXY maleone in every 2000 live birthshave male sex organs, but are sterilefeminine characteristicstallnormal intelligence
85 Klinefelter’s syndrome How many Barr bodies would you expect?
86 Klinefelter’s syndrome How many Barr bodies would you expect?
87 Jacob’s syndrome male XYY Males 1 in 1000 live male births extra Y chromosomesomewhat taller than averagemore activeslight learning disabilitiesdelayed emotional immaturitynormal intelligence, normal sexual development
88 XYY MalesHow many Barr bodies would you expect?
89 Trisomy X XXX 1 in every 2000 live births produces healthy females Why?How many Barr bodies would you expect?
90 Turner syndrome Monosomy X or X0 1 in every 5000 births varied degree of effectswebbed neckshort statureimmature sterile femalesHow many Barr bodies would you expect?
93 Key ConceptsWhat is the goal of the human genome project?What is gene therapy?
94 Bioethics and YouAs you become more aware of scientific advances in genetics, you might realize that with the ability to manipulate genes, there comes responsibility.This ability provides an opportunity to improve the lives of many people.But there is also a potential for errors or intentional misuse of the technology.Go to Section:
95 If two prospective parents suspect they might be carrying recessive alleles for a genetic disorder such as cystic fibrosis or Tay-Sachs disease, how could they find out for sure?Genetic tests have been developed that can spot abnormalities in DNA. Scientists can compare normal sequences with these parents’ DNA to see if they are carriers
96 DNA FINGERPRINTINGAnalyzes sections of DNA that have little or no known function but vary widely from one person to the next – this tool can identify individuals
97 How to do DNA Fingerprinting A sample of DNA with genes and repeats (“junk DNA”) is takenRestriction enzymes cut the DNA into fragments containing genes and repeatsThe DNA fragments are separated according to size using gel electrophoresisRadioactive “probes” showing where the repeats are – this produces a series of bandsThis has been used since the 1980’sIt not only helps to convict criminals but has also freed those who were wrongly accused
98 Our complete set of genetic information HUMAN GENOMEOur complete set of genetic information
99 What is the Human Genome Project? 1990 the US and other countries began trying to sequence all human DNAThis project was completed in 2003They have mapped 20,000 – 50,000 human genesThey know the sequence of 3 billion base pairsNow that scientist know the entire human genome they are trying to figure out how to prevent certain genetic disorders
100 GENE THERAPYThe process of changing the gene that causes a genetic disorder – it is replaced by a normal working geneNormal hemoglobin geneBone marrow cellChromosomesGenetically engineered virusNucleusBone marrowGo to Section:
101 Food for thoughtDo you think it should be legal for people to affect their children’s characteristics?What will happen to the human population if we gain the opportunity to design our bodies?
102 Key Concepts Answered: How is sex determined?All egg cells carry a single X chromosome (23X). However, half of all sperm cells carry an X chromosome (23X) and half carry a Y chromosome (23Y). This ensures that just about half of the zygotes will be 46XX and half will be 46XY. Egg cells contain a single X chromosome. Sperm cells contain either one X chromosome or one Y chromosome.How do small changes in DNA cause genetic disorders?a small change in the DNA of a single gene affects the structure of a protein, causing a serious genetic disorder
103 Key Concepts Answered: Why are sex linked disorders more common in males, than in females?Males have just one X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive.What is nondisjunction, and what problems does it cause?Nondisjunction causes gametes to have abnormal numbers of chromosomes. If nondisjunction occurs, abnormal numbers of chromosomes may find their way into gametes, and a disorder of chromosome numbers may result.
104 Key Concepts Answered: What is the goal of the human genome project? The Human Genome Project is an attempt to sequence all human DNA.What is gene therapy?In gene therapy, an absent or faulty gene is replaced by a normal, working gene.