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Test Class Before Last Class Mendel Dihybrid Crosses Epistasis Gene interaction Pedigrees Probabilities Mendel revisited How do we know if our experimental data is good? Goodness of Fit How well do our observed match our expectations - "Goodness of Fit" How well to our observed "fit" our expectations Geneticists use statistical tests to measure "Goodness of fit" X2 (Chi-squared) test/method Compares the expected to the observed Based on a specific hypothesis X2 test State the Hypothesis In a test cross of heterozygous round seeds we would expect a phenotypic ratio of 1:1 Parental F1 Ww X ww 1:Ww; 1:ww Make predictions (Expectations) Always real numbers Given 40 seeds total Expect 20 round 20 wrinkled X2 test Calculate each class (observed-expected)2 expected Sum each class X2 = 0.2 + 0.2 = 0.4 Interpret x2 value 0.05 (5%) = statistically significant Genetic hypothesis is doubtful 0.01 (1%) = highly significant Reject the genetic hypothesis X2 test Interpret x2 value 0.05 (5%) = statistically significant Genetic hypothesis is doubtful 0.01 (1%) = highly significant Reject the genetic hypothesis Based on degrees of freedom 2 classes of data = 1 degree of freedom (df) 4 classes of data = 3 df Once one event has occurred there are 3 possible combinations left 3 degrees of freedom 7324 seeds (5474 round)
(5474-5493)2 X2 = 5493 X2 = 0.26 + 1831 (1850-1831)2 X2 values for different degrees of freedom and the probabilities associated with the X2 values X2 X2 = 0.4 with 1 df Probability of 0.60 Probability that chance alone (chance that lead to the difference from expected), producing a X2 value equal to or greater than 0.4 would occur in ~60% of the experiments data/experiment is satisfactory (X2 < 0.05 chance alone does not account for the deviation from expected Extensions of Mendel's Laws Dominance What is dominance Co-Dominance Phenotype is not an intermediate between phenotypes Phenotype expressed represents both alleles Restriction Fragment Length Polymorphism (RFLP) Variation in restriction nuclease cutting sequence at a particular site creates DNA fragments of different sizes. In a homozygous organism the fragments are of the same size. In a heterozygous organism, the fragments are of different sizes. What Mendel did not know
The wrinkled seed coat is a mutation in the the SBE1 gene. The mutant is due to the insertion of a transposable element in the wild type smooth seed coat gene. As a consequence, the mutant gene is longer and therefore runs slower in an agarose gel. Co-dominance at a molecular level MN blood antigen (cell surface protein that
presents/elicits an immune response) Two alleles, LM and LN Three phenotypes, M antigen, N antigen and both M and N antigens CFTR gene expression Cystic fibrosis transmembrane conductance regulator Dominance summary Dominance is allelic interaction Interactions of genes at the same locus Does not affect inheritance only expression (phenotype) (the gene product) "eye of the beholder" Dominance depends on the context Penetrance and Expressivity (Muddying the waters) You have the gene but not the phenotype associated with the gene product genotype does not produce the expected phenotype or produces it only a partial phenotype Penetrance The percentage of individuals that have a genotype who are actually expressing the expected phenotype Penetrance The percentage of individuals that have a genotype who are actually expressing the expected phenotype Polydactyly dominant allele but not always expressed 315 people have the genotype but only 250 have extra fingers and toes ~79% penetrant Expressivity The actual extent that a trait is expressed Polydactyly Have a range of phenotypes from complete extra fingers and toes to just a flap of extra skin (skin tag) Different from incomplete dominance Range of phenotypes can occur for homozygote Genotype means what? Things affect how/when/why a gene is expressed Because you have it does not mean you express it Lethality 1905, Lucien Cuenot Crossing yellow mice Could not produce a true breeding mouse 2/3 yellow and 1/3 brown Lethality 1905, Lucien Cuenot Crossing yellow mice Could not produce a true breeding mouse 2/3 yellow and 1/3 brown The color allele for yellow was lethal Lethality 1905, Lucien Cuenot Crossing yellow mice Could not produce a true breeding mouse 2/3 yellow and 1/3 brown The color allele for yellow was lethal 1907, Erwin Baur Snap Dragons (aurea stain yellow leaves) Yellow produced 2/3 yellow 1/3 green leaves Test cross produced 1:1 yellow to green Lethal allele is dominant When present as heterozygote dominant for color When present as homozygote dies If truly dominant both homozygotes and heterozygotes would die (lose the allele) Only can exist as a late/adult onset lethality (Huntington disease) Multiple Alleles More than one allele exists for a gene Type of polymorphism Allelic series Have many alleles but an individual can only have 2 (2 chromosomes carrying 1 copy each) Multiple alleles in Ducks Feather pattern M mallard MR restricted md dusky Genotype MRMR MRM MRmd MM Mmd mdmd Phenotype Restricted Restricted Restricted Mallard Mallard dusky MR > M > md Universal donor Gene Interaction Dihybrid affecting a single specific trait Fruit color (Capsicum annuum pepper) R_P_ Walnut R_pp Rose rrP_ pea rrpp single Epistasis Gene interaction Effect of one gene masks the effect of a different gene Masking gene (epistatic gene) Masked gene (hypostatic gene) Coat color in labradors B_E_ - black, bbE_ - chocolate, __ee, yellow Recessive epistatsis Phenylalanine degradation pathway This pathway shows the steps blocked in various diseases including Alkaptonuria emphasizing both the "One Gene, One Enzyme" but also "Inborn Errors in Metabolism" Each Arrow represents one step in the pathway Epistasis
When genes interact disturbing the expected Mendelian Ratios The expression of the normal (wild type) trait requires the presence of at least one dominant allele from each of two separate genes Epistatic interaction between 2 genes resulting in a F2 phenotypic ratio of 9:7
Epistatic gene/Hypostatic gene One gene is masking another Recessive Epistasis (9:3:4) From the test: Assume that in addition to feather color the two genes above were involved in the same pathway which determines feet color as follows:
a X W Albino (co . x a . xs Dominant Epistasis (12:3:1) Duplicate recessive epistasis (9:7) Interpreting Epistasis 1 Epistasis and Mendelian Ratios Taking everything together Multiple alleles Multiple loci (Gene) polygenic trait Gene interactions Coat color in dogs Some of the loci Black (B) B and b Dilution (D) D and d Ticking (T) T and t Extension (E) Em, E, ebr, e
P Spotting (S) S, si ; s , sW (S_ > T) Albino (C) C, Cch, Cd, cb, c (>>>>)
S Y W S t AsAsCCDDSStt (B_E_) asasBBCCDDsPsPtt as saddle, BCD black, sP spotting, ee all tan AsAsCCDDEEsWsWTT (B_) Solid coat, epistasis with sW Sex Influenced Autosomal trait (follows Mendel's law) that is expressed differently in males versus females Higher penetrance in one of the sexes Goat Beards Bb is dominant in males and recessive in females BbBb and BbB+ Male beard, female beardless Sex-limited characteristic Autosomal trait whose expression is limited to just one sex Zero penetrance in the other sex Chicken plumage (Cock feathering sex limited) Genotype Male Phenotype Female Phenotype HH Hh hh Hen feathering Hen feathering Cock feathering Hen feathering Hen feathering Hen feathering Precocous puberty early onset puberty (< 4 years old), normal, short Male-limited type (P) only expressed in males Male-limited type (P) only expressed in males Defective LH receptor stuck in the on position (stimulates testosterone) Genomic Imprinting Epigenesis
- Altered gene expression not due to genome - Methylated DNA - Birth weight - Prader-Willi and Angelman Syndromes
- Genes sex-influenced expression due to methylation pattern inherited from parent - Dad Angelman, Mom Prader-Wille Anticipation Disease symptoms from generation to generation Earlier onset More progressive disease Myotonic /dystrophy Disease worsened from generation to generation Huntington Earlier onset SSR trinucleotide The environment and genes Environment effects gene expression Temperature-sensitive allele Restrictive temperature The temperature that a variant genotype is expressed Permissive temperature The temperature that the "normal" phenotype is expressed Himalayan allele ...
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This note was uploaded on 04/02/2008 for the course ZOL 341 taught by Professor Dworkin during the Summer '08 term at Michigan State University.
- Summer '08