Biol 135A Mendelian Genetics PDF

Biol 135A Mendelian Genetics (Ch. 14) Rajab  Chapter 14 Lecture Outline Mendel Monohybrid cross-Law of Segregation Dihybrid cross-Law of Independent Assortment Rules of probability Pedigrees Beyond Mendel Human genetic disorders ...

Biol 135A Mendelian Genetics (Ch. 14) Rajab  Chapter 14 Lecture Outline Mendel Monohybrid cross-Law of Segregation Dihybrid cross-Law of Independent Assortment Rules of probability Pedigrees Beyond Mendel Human genetic disorders  Gregor Mendel and his garden peas Why did Mendel Choose the garden pea? Not enough elephants walking around what is the basis for inheritance those areas when mated with themselves 1.Large number of true-breeding varieties. 2.Hybrid peas available. 3.Reproduce fast. 4.Can self-fertilize or cross- fertilize Blending vs particulate hypotheses character - eye color trait - black or brown  Mendel’s First Question: How are EXPERIMENT Characters Inherited? P Generation examining inheritance of one character in hybrids (self fertilization has the potential to have differing offspring) (true-breeding The Monohybrid Cross parents) Purple flowers White flowers Experimental Design P (parental) F1 F1 Generation (hybrids) F2 from F1 monohybrid cross All plants had purple flowers Self- or cross-pollination F3-from selfing F2s What did these results tell true breeding (1p) Mendel?? F2 Generation (w) inheritance of characters is as particles hybrids (2p) 705 purple- 224 white flowered flowered plants plants Mendel’s Model For Explaining These Results–Law of Segregation 1. Genetic variation comes from “heritable factors” (genes) 2. We inherit two “heritable factors” for each character→ alleles – homozygous – hetrozygous 3. In heterozygotes there’s a dominant and recessive allele – genotype – phenotype 4. Alleles segregate randomly into gametes when an individual matures. (They are physically separated on homologous chromosomes.) Each gamete randomly gets one or the other allele → Law of Segregation separation = meiosis phenotype: what you see (color) genotype: homo or hetero (dom/rec.)  How did Mendel know if an unknown plant with a dominant phenotype was homozygous dominant or heterozygous? – Ans: Testcross use truebreeding recessive Modern Explanation for These Results–Law of Segregation Enzyme C T A A A T C G G T G A T T T A G C C A Allele for purple flowers CTAAATCGGT Enzyme that helps synthesize purple pigment Locus for Pair of flower-color gene homologous chromosomes One allele results in Allele for sufficient white flowers Absence of enzyme pigment A T A A A T C G G T T A T T T A G C C A ATAAATCGGT Figure 14.4 2nd Q: if a plant has purple flowers and yellow seeds, does the purple allele always go with the yellow allele? Mendel’s Second Question: Are different characters inherited independently of one another or are they mendel got this one inherited dependently? Dihybrid Cross – Results?? Independent Assortment 2 gametes when Y and R are on same chromosomes (2 chrom) 4 gametes when they are on separate ones (4 chrom) —> this is the correct one because they are inherited independently // y is independent of r) This is what Mendel concluded: different characters assort independently from one another A modern way to say this: genes that are located on different chromosomes, assort independently during meiosis. Another way to say this is as follows: If alleles A and B are on different non homologous chromosomes, which gamete A lands in does not have any influence on which gamete B lands in. Probability Prob. Scale: 0-1: 0 never occurs, 1 certain to occur The probabilities of all possible outcomes for an event must add up to 1 Independent events: events whose outcome is unaffected by other previous or simultaneous events Product Rule: The probability of two (or more) independent events occurring together can be calculated by multiplying the individual probabilities of the events. Sum Rule: If a particular outcome can happen through more than one independent event, then the probability of the outcome is the sum of the probabilities of all possible independent events that can produce the outcome. Using the rules of probability to predict 9:3:3:1 Phenotype Ratio Figure 14.UN01 (1) What is prob of YYRR offspring from a dihybrid cross? What about YyRR? (2) In the following cross, PpYyRr x Ppyyrr, what fraction of offspring are expected to exhibit the recessive phenotype for at least two of the three characters?  (3) In the following cross, PpYyRr x Ppyyrr, what fraction of offspring are expected to exhibit the recessive phenotype for at least one of the three characters? First, list all possible offspring genotypes that would give the opposite of this outcome PpYyRr and PPYyRr Second, calculate each genotype probability PpYyRr: ½ X ½ X ½ = 1/8 PPYyRr: ¼ X ½ X ½ = 1/16 Third, add the individual probabilities and subtract from 1. 1/8 + 1/16 = 3/16 1-3/16 =13/16 = fraction recessive for at least one  What is the prob of more than one being recessive????  (4) What is the probability that 2 out of five offspring plants will have purple flowers when the parents are both heterozygous? This problem requires the binomial expansion. How do you recognize it? two possible outcomes no specific order of outcomes is given Pedigree analysis  (5) Homer and Marge each have a sibling with cystic fibrosis. Neither Homer nor Marge nor any of their parents have the disorder (nor have they been tested to show whether they have the recessive allele). What is the probability that if they have a child, the child will have cystic fibrosis? Answer: First draw pedigree – Homer and Marge’s parents were carriers of the recessive (mutated) allele for CF (how do we know?). – For Homer and Marge to have a CF child, four events MUST happen: 1. Homer is a carrier (P = 2/3) 2. And Marge is a carrier (P = 2/3) 3. And Homer must donate the recessive allele (P = ½) 4. And Marge must donate the recessive allele (P = ½) 2 2 1 1 1 So multiply these probabilities: 𝑥 𝑥 𝑥 = 3 3 2 2 9  (6) What is the probability Homer and Marge will have an unaffected child (without CF)? Answer: there are 4 possible ways this can happen: – Homer carrier and Marge carrier and child hetero or HD: 2/3 X 2/3 X ¾ = 1/3 – Or Homer carrier and Marge HD and child hetero or Q 6 alternative HD: 2/3 X 1/3 X 1 = 2/9 method: 1-1/9 – Or Homer HD and Marge carrier and child hetero or = 8/9 HD: 1/3 X 2/3 X 1 = 2/9 – Or Homer HD and Marge HD and child HD: 1/3X1/3X1 = 1/9 1 2 2 1 8 – So add up these probabilities: + + + = 3 9 9 9 9  (7) What is prob that it is impossible for Homer and Marge to Q 7 alternative method: have a child with CF? (i.e. they will never ever ever ever have Answer to #7 is prob at children with CF?) least one of parents is Answer: to get this result, three genotype combos of Homer homozygous dominant. and Marge are possible: So, 1-(prob neither is – Homer is heterozygous AND Marge is homozygous homozygous dominant) dominant (2/3 x 1/3) = 2/9 = answer – Or Homer is homozygous dominant AND Marge is 2 2 1-( 𝑥 ) = 5 heterozygous (1/3 x 2/3) = 2/9 3 3 9 – Or Homer AND Marge are both homozygous dominant (1/3 x 1/3) = 1/9 2 2 1 5 – So add up the three: + + = 9 9 9 9 Going Beyond Mendel: six big ideas I. Dominance Relationships: – Complete dominance – Incomplete dominance – Codominance II. Multiple Alleles III. Pleiotropy IV. Epistasis V. Polygenic VI. Environment effect VII. Human genetic conditions I. Dominance Relationships: (1) Complete dominance – Dom allele makes enough functional protein even when it occurs alone (i.e. in heterozygous individuals) – Heterozygous genotype→ dominant phenotype NOT making white pigment; just the absence of any other – Recessive allele does not express the pigment protein or expresses a non functional version I. Dominance Relationships: (2) Incomplete dominance: – One copy of dom. allele not enough → intermediate phenotype (e.g. snapdragons) – Hets don’t make enough functional protein – dominance relationships differ btwn organismal and biochemical levels → e.g. Tay-Sachs autosomal + recessive complete dominance, in use this symboling when working w/ heterozygous incomplete dominance parents thats incomplete dominance because they have a higher level than homo dominance but less than homo recessive I. Dominance Relationships (3) Codominance: – 2 alleles show 2 diff functional proteins and phenotypes e.g. people with blood type AB are IAIB show both the A and B carbohydrate antigen on RBC II. Multiple Alleles: – most genes in a population with more than two alleles – e.g. ABO blood groups III. Pleiotropy: when a single gene has multiple phenotypic effects Pleiotropy of the beta globin gene mutation ability of a gene to affect individuals in multiple ways e.g. sickle cell anemia and cystic fibrosis in example affected shape and symptoms *ALL genes are pleotropic!!! IV. Epistasis: Epi= on top // e genes = boss/on top of b a gene at one locus can have an effect on the expression of a gene at another locus dihybrid cross: e.g. coat color in mammals - both hetero - mendel- 9:3:3:1 B genes:code for pigment (products) - BB —> black pigment epistasis: - Bb -> black - 9:3:4 - bb —> brown - the b doesnt matter because if the e doesnt e genes: code for transport protien that use it it isnt going to moves pigment into hair (trucks) affect anything - EE -> yes - Ee -> yes - ee -> no V. Polygenic inheritance gradient / not just black or white or yes or no some characters vary in a population along a continuum common for quantitative characters that are determined by the interaction of several loci e.g. height, skin color (378 genes thought to contribute to skin color!!!!!!!!) character phenotype show a normal bell- shaped distribution Polygenic Inheritance of Eye Color  VI. Environmental Effect: Environmental conditions can interact with genotype to produce a final phenotype Figure 14.14 The effect of environment on phenotype in hydrangea Neutral to low acidity Highly acidic soil rich in soil poor in aluminum aluminum  Human Mendelian Genetics: Recessive Disorders & Carriers Albinism Cystic Fibrosis Sickle-cell anemia Tay Sachs Alkaptonuria – Dominant disorders: Achondroplasia Huntingtons recessive “wildtype” phenotype - the norm for the population aa x aa —> Aa bc of spontaneous mutations in the germ line cells - so it wont affect the parents Progeria – Multifactorial disorders: these have genetic and environmental components e.g. heart disease. Diabetes, cancer, alcoholism Cleft palate and cleft lip purely envionmental - stress