Lecture 4: "Deviations From Mendelian Ratios"

Genetics Lecture No. 4: Deviations From Mendelian Ratios Monday January 21 , 2013 Lucien Cuénot’s Odd Yellow Mice & Pleiotropy: -Lucien Cuénot, one of the first individuals to test Mendelian principles using animals, was studying coat colour in mice when he discovered strange anomalies regarding the expected 3:1 Mendelian ratios of the F1 offspring. Matings of inbred agouti mice (recessive allele) to yellow mice (dominant allele) always resulted in a 1:1 ratio of yellow to agouti, where the yellow mice are always heterozygous. Matings of yellow to yellow mice always resulted in a 2:1 ratio of yellow (all heterozygous) to agouti. It was later y y determined that two copies of the dominant yellow coat allele (A A ) was lethal to the bearing mouse. This is a clear-cut example of pleiotropy, a phenomenon in which a single gene determines a number of y distinct and seemingly unrelated characteristics. In the mice, A was shown to be dominant to A with respect to coat colour, while A was shown to be recessive to A with respect to viability. Types Of Lethal Alleles: -Early onset alleles are cases where the gene is necessary for cellular function as well as death at embryogenesis or early on in life (e.g. Cuénot`s mice). Late onset alleles are cases where the gene is essential for survival, but not until the individual has matured. Semi lethal alleles are cases where the gene kills some mutant individuals in the population, but not all. Conditional alleles are where the mutation is only lethal under certain environmental conditions (e.g. fruit fly mutants and temperature). Fruit fly Mutants & The Chi Square Test: -In observing eye colour in fruit flies, red is the wild type and is dominant to white. In a hypothetical cross between two heterozygotes, the observed ratio of 3470:782 (red:white) deviates from the expected Mendelian ratio of 3:1. The chi square test is a calculation that can be used to tell whether a deviation from Mendelian ratios is a genetic phenomenon or due to random chance (sampling error). The greater the difference between the observed and expected values, the less likely the deviation is going to be due to sampling error (a genetic phenomenon). By using the conventional critical value of p < 0.005 and determining the degrees of freedom to be 1 (number of classes – 1), it was concluded that the observed differences in eye colour were a genetic phenomenon (white flies carried a conditional lethal allele). Single-Gene Inheritance (Incomplete Dominance & Codominance): -Incomplete dominance is where the heterozygote expresses a phenotype that is different than either of the parents; a blending of traits is observed in the heterozygous phenotype. In snapdragon flowers, red colour denotes a functional gene (and white colour a non-functional one), so incomplete dominance will produce a pink colour in heterozygotes for that gene. Codominance is where the heterozygote expresses a phenotype in which both traits are observed equally; both alleles are observed in the heterozygous phenotype. E.g. Human glycolipid blood types. Single Gene Inheritance (Dominance Series): -Another extension to Mendelian genetics is number of possible alleles for a given gene. Where Mendel was focusing on genes with only two alleles, some cases (such as in lentils) you can observe as many as five different phenotypes having to do with colouring. Since dominance relationships are only meaningful when considering two specific alleles, it is necessary to set up a series of controlled crosses that result in a dominance series. The formula for determining the kinds of genotypes given the number of alleles (n) is n (n+1) / 2, while the formula for determining the kinds of heterozygotes given the number of homozygotes (n) is n (n-1) / 2. Penetrance & Expressivity: -Variable penetrance is where all individuals in a population have the same genotype at a given locus, but some show the expected phenoty