Week 12 Genetics I Chapter 11 pages 189-201 Genetics II Chapter 11 pages 202-209 EXAM III RESULTS Total Students = 39 Total Pass= 15 (38.5%) Total Fail= 24 (61.5%) Class Average = 63 Top Score = 94 Low Score = 32 EXAM III GRADE DISTRIBUTION 9 8 8 8 7 7 6 6 5 5 Number of Students 4 3 3 2 2 1 0 90-100 80-89 A B 70-79 C 60-69 D 50-59 F 40-49 F 30-39 F TROUBLE SPOTS Questions answered incorrectly: #2 (61.5% (24/39)) #3 (41% (16/39)) #9 (46% (18/39)) #19 (67% (26/39)) #26 (47% (23/39)) #49 (69% (27/39)) #s 10 and 50 were well answered in general #49 A. MEIOSIS B. Pairing of homologous chromosomes only occurs in meiosis crossing over Pairing of x-somes HOMEWORK Chapter 12 ALL including Self-tests EXAM III Extra Credit- DUE MAY 10th Aneuploidy Euploidy= Correct number of chromosomes in a species Aneuploidy= A change in the number of chromosomes due to nondisjuction CHANGES IN CHROMOSOME STRUCTURE Changes in chromosome structures are mutations X-somes can break due to radiation, organic chemicals and viruses End of chromosomes break and can go back together improperly which leads to chromosomal mutations: Deletions Duplications Translocations Inversions Deletions Inversions Duplications Translocations DNA exists as chromatin or as a chromosome DNA- Deoxyribonucleic Acid A POLYMER of NUCLEOTIDES How do we know that certain complications will arise if genes are added or deleted to portions of chromosomes? Through the Study of Genetics! Genetics is the study of biologically inherited traits Ex. How will the deletion of section ‘a’ affect disease? Genomics is the study of all of the genes in an organism Genetics and Genomics ‘Inherited traits are determined by the elements of heredity that are transmitted from parent to offspring in reproduction; these elements of heredity are called genes.’ DNA is the molecule of heredity Gregor Mendel, 1822-1884 Austrian Monk Developed ‘Particulate Theory of Inheretance’ By studying Pea Plants in the 1860s Combined Math and Biology! Used statistics and laws of probability to study biology The Father of Genetics Darwin 1809-1882 Mendel studied garden pea plants to understand the units of heredity WHY? At the time, the ‘Blending Concept of Inheritance’ was widely accepted Blending Concept of Inheritance= an offspring’s genetic makeup is intermediate to that of its parents Ex. A cross between red and white flowers will only generate PINK flowers Is this true? NO!! Because… Red, Pink and White flowers result in the 2nd Generation! Diverse forms could not evolve if the blending theory was correct. If we only had intermediate forms with little variation, how could all of the diversity we see have evolved? •Confused both Mendel and Darwin •Genes had not been discovered and would not be discovered until 1869 by Friedrich Miescher •The molecular makeup of genes was discovered, but the function of genes was still not well understood. •By 1900 it was understood that chromosome number is nearly constant in the cells of any species. •Seemed likely that chromosomes were carriers of genes. How did Mendel and others come to the conclusion that chromosomes were the carriers of genes? Through the study of phenotypes and crossings of pea plants with various traits PHENOTYPE GENOTYPE The set of an organism’s observable properties resulting from the interaction of the organisms genotype with its environment The genes present in a particular organism or cell ‘ATCCGCATTACG’ Mendel’s 7 Pea Plant Traits P = Parental Generation F1= First Generation F2= Second Generation 1. 2. 3. 4. Garden Pea Plant Pisum sativum 5. 6. 7. Mendel’s Particulate Theory of Inheritance • Mendel used the scientific method to understand inheritance in pea plants • He created ‘pure’ or ‘true-breeding’ lines of plants for specific traits (ex. Round or smooth seeds, purple or white flowers…) • He observed and tracked these phenotypes through multiple generations of pea plants • Based on his studies, he determined that hereditary information is passed from parents to offspring in the form of discrete “particles” (which we now refer to as GENES) Why study the Garden Pea Plant? • Easy to cultivate • Short generation time • Can self pollinate - Able to create ‘true-breeders’ • Can cross pollinate by hand • Traits easy to observe • Can observe dominant or recessive characteristics ‘True-Breeding’ - Anther contain Sperm - Ovules in ovary contain Eggs - Pea plants are able to ‘selfpollinate’ - Therefore, offspring are identical to the parents - Mendel bred plants ‘true’ to ensure the purity of each trait Why secure the purity of each trait? • Had to ensure that the trait he was observing was not confounded by other discrete particles • Ex. He had to make sure that a white colored flower was truly white before making any crosses • His experiments would have failed because he would have observed different outcomes each generation Cross-Pollination After self pollinating plants for several generations to obtain ‘true-breeding’ plants Mendel used the anther from one truebred plant to pollinate the Stigma of another true-bred plant= Cross Pollination From plant A onto the stigma of plant B Mendel’s Hypothesis Hypothesis Hereditary information is passed from parents to offspring in the form of discrete “particles” Mendel’s Observations (3:1, D:R) Mendel’s Laws Based on his observations of cross-pollination studies: 1 LAW OF SEGREGATION 2 LAW OF INDEPENDENT ASSORTMENT LAW OF SEGREGATION Based on the hypothesis that if the blending theory of inheritance were true, then a cross should yield an “intermediate” phenotype in comparison to the parents Ex. Tall plant x Short plant = Medium plant Mendel tested this by crossing plant varieties that differed by only 1 single trait… LAW OF SEGREGATION Mendel performed ‘reciprocal’ crosses: Dusted pollen of Tall plants onto Short plants Dusted pollen of short plants onto Tall plants All F1 resembled the TALL parent! NOT intermediate! Mendel allowed the F1s to self-pollinate ¾ of the F2 plants were Tall and ¼ of the F2 plants were short! ALL F1s were Tall No intermediates observed! ALL F1s would have had the same genetic makeup because the parents were bred true. ALL of the F1 generation plants would have had a Tt genotype One T from parent 1 (bred true for TALL) and one t from parent 2 (bred true for SHORT) What happens when you cross two F1 generation plants? X Gametes A true-bred TALL plant gametes will only be T A true-bred SHORT plant gametes will only be t Gametes THEREFORE, the ONLY resulting GENOTYPE for the F1 generation is T t F1 CROSS X The F1s are all Tt, therefore when Cross with each other It is a ‘mono’(one type) ‘hybrid’ (Tt) cross What will the GENOTYPES of the GAMETES look like for this MONOHYBRID CROSS? What will the GENOTYPES of the GAMETES look like for this F1 MONOHYBRID CROSS? F1 F1 T t T t F1 GAMETES F2 GENOTYPES and PHENOTYPES WHAT IS THE PHENOTYPIC RATIO OF TALL TO SHORT? WHAT IS THE GENOTYPIC RATIO OF TALL TO SHORT? 3:1 TALL: SHORT Dominant:Recessive Monohybrid crosses ALWAYS result in a 3:1 ratio The SHORT trait is masked by the TALL trait in the F1 generation and is observed in the F2 generation TALL is a dominant trait and SHORT is a recessive trait LAW OF SEGREGATION 1 Each individual has two factors for each trait 2 The factors ‘segregate’ during the formation of gametes 3 Each gamete contains only one factor from each pair of factors 4 Fertilization gives each new individual two factors for each trait (haploiddiploid) PAGE 192 Dominance ‘Tallness’ in pea plants is dominant to ‘shortness’ Tall = T Short= t If parent 1 = TT (tall plant) and parent 2 = tt (short plant) ALL F1 generation plants will be Tt Dominance Genes occur at a particular ‘locus’ on a chromosome Alternative versions of the same gene are called ‘alleles’ The dominant allele masks the expression of the recessive allele Alleles= Alternative versions of the same gene MOM A gene occurs at a particular locus DAD If purple is dominant to white, the purple phenotype is observed, but you are a carrier for white! Remember: only 1 allele of each trait is in a gamete (meiosis!) GENOTYPES TT = Homozygous dominant Tt = Heterozygous tt = Homozygous recessive Phenotypes (Tall Plant) (Tall Plant) (Short Plant) PUNNETT SQUARES • Used to predict breeding outcomes • Able to calculate probability of traits Example: Tt Tt tt tt MENDEL’S LAW OF INDEPENDENT ASSORTMENT Mendel experimented with plants that differed in 2 traits The plants are hybrid in 2 ways therefore the crosses between the F1 generation are ‘DIHYBRID CROSSES’ 2 traits Tall Green pods 2 traits short Yellow pods DiHybrid Cross Cont.’d X F1 GAMETES ? ? Sperm Eggs DiHybrid Cross Cont.’d X TG TG Tg Tg tG tG tg tg F1 GAMETES Sperm Eggs Mendel’s Dihybrid Cross Hypothesis I If the dominant factors always segregate together (=TG) and the recessive factors segregate together (=tg), then there would be two phenotypes among the F2 plants ONLY, tall plants (T) with green pods(G) and short plants (t) with yellow pods (g) Did Mendel observe this to be true? NO!!! Mendel’s Dihybrid Cross Hypothesis II If the four factors (T, G, t, g) segregate into the F1 gametes independently, then there would be four phenotypes among the F2 plants Tall and green pods Tall and yellow pods Short and green pods Short and yellow pods Did Mendel observe this to be true? YES!!!!! Mendel’s Dihybrid Cross Observations 9:3:3:1 9:3:3:1 Dihybrid crosses always have this phenotypic ratio!!! LAW OF INDEPENDENT ASSORTMENT 1 Each pair of ‘factors’ segregates (assorts) independently of the other pairs 2 All possible combinations of factors can occur in the gametes PAGE 194 Mendel and Meiosis Homologous pairs of chromosomes line up randomly at the metaphase plate This allows for independent segregation during gamete formation Probability Wouldn’t it be nice to know the outcome of a particular cross? - Punnett squares enable us to calculate the chance or probability of genotypes and phenotypes of offspring - How likely is it that an offspring will inherit a specific set of two alleles, one from each parent? The Product Rule of Probability What is the chance of offspring having: EE 1/2 x 1/2 = 1/4 Ee 1/2 x 1/2 = 1/4 eE 1/2 x 1/2 = 1/4 ee 1/2 x 1/2 = 1/4 The Product Rule of Probability In a monohybrid cross, we know that each Child has a 25% (1/4) chance of having attached Earlobes The SUM Rule tells us that we can add together all of the same phenotypic traits: Ex. ¾ or 75% of the children will have unattached Earlobes (¼ + ¼ + ¼ = 3/4) Ratios MONOHYBRID Crosses ALWAYS result in a: 3:1 ratio 3 Dominant: 1 Recessive trait (Rr x Rr) DIHYBRID Crosses ALWAYS result in a: 9:3:3:1 ratio 9 Dominant: 3 Dominant and Recessive: 3 Dominant and Recessive :1 Recessive (TtGg x TtGg) YOUR TURN! In Pea Plants, yellow seed color (Y) is dominant over green seed color (y). When two heterozygous plants are crossed, what percentage of plants would have yellow seeds? ¾ or 75% What percentage would have green seeds? ¼ or 25% YOUR TURN! In humans, pointed eyebrows (B) are dominant over smooth eyebrows (b). Mary’s father has pointed eyebrows, but she and her mother have smooth eyebrows. What is the genotype of the father? Mary’s father can’t have a BB genotype otherwise all of the offspring would have pointed eyebrows. He can’t be bb otherwise he would have smooth eyebrows. He MUST have a Bb genotype in order for Mary to have smooth eyebrows. Testcrosses Testcrosses are performed in order to figure out the genotype underlying a particular phenotype Mendel performed test crosses of F1 individuals with “true-bred” individuals to figure out the laws of segregation (that alleles segregate independently during gamete formation) Testcrosses One-trait test cross: Individual w/ Dominant phenotype is heterozygous Individual w/ Dominant phenotype is homozygous Testcrosses Two trait test-crosses: Individual w/ dominant phenotype is crossed with one having the recessive phenotype Is the fly on the left heterozygous or homozygous for wing and body color? WE HAVE NO IDEA SO WE MUST TESTCROSS TO DETERMINE THE GENOTYPE!! For fruit flies (Drosophila melanogaster) we know: L = long wings l = short (vestigial) wings G=gray bodies g =black bodies What are the genotypes for these flies? The black fly with short wings MUST be llgg If these are the offspring between the homozygous recessive (black/short wings) and the gray body with long wings, what was the gray/long fly’s genotype? llgg x ? = What is the genotype for the gray/long fly? For fruit flies (Drosophila melanogaster) we know: L = long wings l = short (vestigial) wings If Dominant for both traits= LLGG If Heterozygous for both traits = LlGg G=gray bodies g =black bodies llgg If Dominant Homozygous: LLGG x llgg Gametes Gametes LG LG LG LG lg lg lg lg Punnett Square X lg lg lg lg LG LlGg LlGg LlGg LlGg LG LlGg LlGg LlGg LlGg LG LlGg LlGg LlGg LlGg LG LlGg LlGg LlGg LlGg ALL of the flies would have the same phenotype if the gray/long fly had a LG genotype!! We know these are the offspring and they are not all gray with long wings!!! So….. If Dominant Homozygous: LlGg x llgg Gametes Gametes LG Lg lG lg lg lg lg lg Punnett Square lg lg lg lg LG LlGg LlGg LlGg LlGg Lg Llgg Llgg Llgg Llgg 25%=Long/Black lG llGg llGg llGg llGg 25%=Short/Gray lg llgg llgg llgg llgg 25%=Short/Black X 25%= LlGg, 25%= Llgg, 25%= llGg, 25%= llgg 25%=Long/Gray MUST be heterozygous for both traits!! This is the only way a homozygous recessive fly could have been produced! When crossing a heterozygous for two trait Individual w/ an individual recessive for both Traits the ratio is always: 1:1:1:1 Mendel’s Laws and Human Genetic Disorders Two types of human genetic disorders: 1 Autosomal (x-somes other than X or Y) – Recessive – Dominant 2 X-linked (x-somes that are X or Y) Autosomal Patterns of Inheritance Autosomal Dominant Individual with AA or Aa HAS the disorder a = recessive Autosomal Recessive Invididual with aa HAS the disorder A= dominant Pedigrees Pedigrees are used to track patterns of inheritance of a particular condition and to determine dominance or recessiveness For Example: = MALE = FEMALE = A UNION = A CHILD Pedigrees -The shaded/colored shapes do not indicate whether the person is dominant or recessive -Only indicates that the person is affected Pedigrees In these pedigrees, which is autosomal dominant and which is autosomal recessive? = MALE = FEMALE I Only the Child is affected II Only the Parents are affected Aa Aa aa Autosomal recessive HAS disorder Autosomal RECESSIVE Most affected children have unaffected parents Heterozygotes (Aa)have an unaffected phenotype Two affected parents will always have affected children Close relatives who reproduce are more likely to have affected children Both males and females are affected with equal frequency Aa Aa aa Autosomal DOMINANT Affected children will usually have an unaffected parent Heterozygotes (Aa) ARE affected Two affected parents can produce an unaffected child Two unaffected parents will not have affected children Both males and females are affected with equal frequency Carriers In Pattern I, the parents are Carriers for the condition, but they do not exhibit the condition themselves Is this pattern Autosomal Dominant or Recessive? *The double line indicates inbreeding/breeding Between closely related individuals (Inbreeding increased frequency of obtaining the disorder Is this pattern Autosomal Dominant or Recessive? Note that BOTH heterozygotes HAVE the condition Autosomal Recessive Disorders 1 Methemoglobinemia 2 Cystic Fibrosis 3 Nieman-Pick Disease Methemoglobinemia An accumulation of methemoglobin in the blood causing the blood to appear blue instead of red skin appears blue in color Hemoglobin Methemoglobin Those affected lack enzyme diaphorase that converts Methemoglobin back to hemoglobin (enzyme is coded for in gene on x-some 22) Autosomal RECESSIVE trait Cystic Fibrosis (CF) • Most common lethal genetic disease among Caucasians in the US (1/20=carrier, 1/2000 newborns has the disease) • Caused by a defective chloride ion channel (protein channel) located in the cell membrane • Cl- ions fail to pass through the channel which in turn does not allow Na+ or water to pass • Lack of water leads to thick mucus in the bronchial tubes and pancreatic ducts Cystic Fibrosis (CF) Life expectancy is usually into the teens and twenties, but some people can live as many as 35 years with the disease Gene therapy is currently being researched to correct the defective gene that produces the faulty protein CFTR= Cystic Fibrosis Transmembrane Conductance Regulator The CFTR gene is located on Chromosome 7 Summers of 1998 and 1999 Studied Cystic Fibrosis by researching the effect of various toxins on the regulation of Chloride secretion in dogfish shark rectal glands in Mount Desert Island Biological Laboratories in Mount Desert Island, Maine Performed dogfish shark rectal gland perfusions Squalus acanthias Nieman-Pick Disease Caused by defective versions of the same gene located on chromosome 11 Normally, Gene codes for enzyme, sphingomyelinase which breaks down sphingomyelin (a lipid) Without proper functioning enzyme, lipid droplets accumulate in the cells of the liver, lymph nodes and spleen Type A= lipid droplet buildup in brain neurological disorders Type B= milder form, protein has some function Children present with persistant jaundice, feeding difficulties, enlarged abdomen, pronounced mental retardation Autosomal Dominant Disorders 1 Osteogenesis Imperfecta 2 Hereditary Spherocytosis Osteogenesis Imperfecta • Autosomal dominant disorder • Caused by mutations in 2 genes needed to synthesize type I collagen • Defective collagen I is produced • Results in weak, brittle bones • Defective collagen can combine with normal collagen and can cause structural defects • Incidence=1/5,000 live births • Treated with drugs Hereditary Spherocytosis • Autosomal dominant genetic blood disorder • Caused by defective copy of ankyrin-1 gene found on x-some 8 • Leads to defective protein normally responsible for the structure and shape maintenance of red blood cells (RBCs) • RBCs become spherical and burst easily due to osmotic stress • Incidence = 1/5,000 • Some cases (25%) are spontaneous mutations and are not inherited by either parent Mendel’s Laws and Human Genetic Disorders Two types of human genetic disorders: 1 Autosomal (x-somes other than X or Y) – Recessive – Dominant 2 X-linked (x-somes that are X or Y) X-Linked Inheritance • Refers to genes that are carried on the X chromosome • Chromosome theory of inheritance (Thomas Hunt Morgan, 1900s)- specific alleles correspond specifically with the X chromosome • The Y chromosome lacks these alleles • Males always receive an X-linked recessive mutant allele from the female parent, therefore sex linked recessive traits appear more frequently in males • Males can not be carriers for X-linked traits • Males express whatever allele is present on the xchromosome and are therefore ‘hemizygous’ for X-linked traits Morgan’s Observations Used fruit flies (Drosophila melanogaster) b/c they have the same chromosome pattern as humans. White eyes only Observed in Males! Males can only Inherit the recessive Allele from the Female parent Note: the allele is now associated with the X chromosome The F1s will all have red eyes because the female is XR homozygous dominant! What will the F1 gametes look like? XR Y XR Xr The F1 Cross Result of F1 cross is that only 1 male has white eyes Females will only have white eyes when they receive a recessive allele from both parents Human X-linked Recessive Disorders 1 Color Blindness 2 Hemophilia 3 Muscular Dystrophy 4 Adrenoleukodystrophy 5 Menkes Syndrome Color Blindness • 3 classes of cone cells in the retina of the human eye and each contains either: 1. Blue-sensitive pigment proteins 2. Red-sensitive pigment proteins 3. Green-sensitive pigment proteins Red and green sensitive pigment proteins are on the X-chromosome Blue-sensitive pigment proteins are autosomal Usuallly passes from grandfather to grandson through a carrier daughter X-linked Recessive Pedigree 8% of Caucasian males have red-green colorblindness Bright Green= tan Olive green= brown Reds= reddish brown Some only see yellow, blue, black white and gray Hemophilia 1/10,000 males is a hemophiliac Two types: Hemophilia A- due to absence/minimal presence of clotting factor VIII Hemophilia B- due to absence of clotting factor IX Hemophiliacs lack the ability to clot blood or they clot blood very slowly Hemophilia: a Royal Pain Queen Victoria Queen of England (and Ireland) b.1819- d.1901 9 children Hemophilia “A Royal Disease” Other Types of Inheritance 1 Multiple Allelic Traits 2 Incomplete Dominance and Incomplete Penetrance 3 Pleiotropic Effects 4 Polygenic Inheritance Multiple Allelic Traits When traits are controlled by multiple alleles, the gene exists in several allelic forms Ex. Human blood types are A B O There are 3 possible alleles that determine the blood type BUT…. The A B O blood type is controlled by a single gene pair Alleles determine the presence or absence of antigens on red blood cells IA = A antigen on red blood cells IB = B antigen on red blood cells i = Neither A nor B antigen on red blood cells Possible phenotypes or genotypes: Phenotype Genotype A IAIA, IAi B IBIB, IBi AB IAIB O ii CODOMINANCE Inheritance of blood types in humans is an example of Codominance Both IA and IB are fully expressed in the presence of the other A person who is IAIB will have blood type AB IA is not dominant over IB IB is not dominant over IA IA and IB are dominant over ii AO AO AA AA BO BB AB Universal Recipient OO Universal Donor Incomplete Dominance and Incomplete Penetrance Incomplete Dominance: When the heterozygote (Aa) exhibits an intermediate phenotype Incomplete Penetrance: When the dominant allele in a heterozygote does not lead to the dominant phenotype The dominant allele may not always determine the phenotype Incomplete Dominance R1 = allele for red pigment R2 = allele for no pigment Incomplete Penetrance Ex. Polydactyly (extra digits on hands, feet or both) Is inherited as autosomal dominant BUT, not all individuals exhibit the trait who Inherit the dominant allele Other genes may influence the appearance of the trait Pleiotropic Effects Occurs when a single mutant gene affects two or more distinct, unrelated traits Ex. Sickle-cell disease Results from a mutation in gene coding for hemoglobin polypeptide Mutation causes change in 1 amino acid in the hemoglobin polypeptide Causes RBCs to be sickle-shaped -Slows blood flow -Decreased O2 carrying capacity -Clogs blood vessels -Resistant to Malaria! -Cells have shorter life span -Severe Anemia Polygenic Inheritance The expression of a trait is controlled by two or more sets of alleles at different loci on different chromosomes =polygenes (each allele contributes to the phenotype) Dominant alleles have a quantitative effect on the phenotype= they are additive This leads to ‘multifactorial traits’continuous variation in phenotypes and genotypes Ex. To what degree does a gene contribute to a trait? How much is due to Environment? The study of this kind of inheritance= Quantitative Genetics (estimates of heritability- I did this by breeding fish!!) Doiminant pairs of genes Multiple outcomes due to several pairs of genes controlling a trait Individual genes of a polygenic trait follow Mendel's laws, but together do not produce Mendelian ratios =bell shaped curve Orange shading represents environmental influence WHAT KIND OF HUMAN TRAITS EXHIBIT POLYGENIC/MULTIFACTORIAL INHERITANCE? WHAT KIND OF HUMAN TRAITS EXHIBIT POLYGENIC/MULTIFACTORIAL INHERITANCE? QUANTITATIVE TRAITS: • Skin color (allele frequencies are the best indicator of shared heritage in a population, therefore, skin color alone does not effectively indicate a person's ethnic and genetic background, sun exposure is an environmental factor) • Height (varies continuously in a bell shape distribution, Diet and health are environmental factors) • Hair color (little environmental influence) • Body Mass (Diet and health are environmental factors) • Finger print patterns (environmental influence possible during gestation) • Eye color (little environmental influence, five human eye colors, interact additively) HAIR COLOR – Hair color is controlled by alleles on chromosomes 3, 6, 10, and 18. – The more dominant alleles that appear in the genotype, the darker the hair. Pepper Color Gene 1: R= red r= yellow Gene 2: Y= absence of chlorophyll (no green) y= presence of chlorophyll (green) Pepper Color Genotypes: Phenotypes: R-/Y- : (red/no chlorophyll) R-/yy : (red/chlorophyll) rr/Y- : (yellow/no chlorophyll) rr/yy : (yellow/chlorophyll) Red Brown/orange Yellow Green “-” Indicates that genotype could be hetero or homozygous Pepper Color • Try crossing a brown pepper (RRyy) with a yellow pepper (rrYY). • Which trait will your offspring (F1 generation) produce? • What traits are produced when you cross two of the peppers found in the F1 generation? THIS WEEK IN YOUR LAB DNA Fingerprinting: Individual 1 2 3 4 5 6 7 8 9 10 Restriction Fragment Length Polymorphisms (RFLPs)