Gregor Mendel Versuche über PflanzenhybridenThe starting material“Pure-breeding line”“An SCN9A channelopathy causes congenital inability to experience pain” Nature Dec. 14, 2006William Ernest Castle – founder of mouse genetics (UCB 1936-1962)Mendel picked the pea as the system. What traits to pick?Slide 7The reaffirmation of a known phenomenonQualitative (“simple”) traitQuantitative (“complex”) traitNot Mendel’s faultThe genesis of the famous termSlide 13Inverting the direction of the cross does not alter the phenotype of the hybridWhat to do with the hybrid (i.e., the F1 plants)?The dataA bit of metaanalysisBrilliant in BrünnAnalysis of the grandchildrenSlide 20Mendel, humble son of a peasant family, pollinating textbooks all over the world for the rest of time with his nomenclatureAnd now (drum roll) – the first lawSlide 23Slide 24Slide 25Slide 26Brilliant in Brünn, part II“Brilliant” isn’t strong enough This is “swish central” Nothing but net.A useful termAn awful, awful term: “monogenic trait”Slide 31Slide 32Slide 33Slide 34Slide 35In what sense is blood clotting a “monogenic” trait?Manhood – a monogenic trait Note: SRY directly causes the conversion of a female embryo to a male oneMotherhood – a monogenic trait?!Slide 39Slide 40In other wordsOne more thingSlide 43Next timeMCB140, 29-08-07 1Gregor MendelVersuche über PflanzenhybridenThe First LawMCB140, 29-08-07 2The starting material“In all, 34 more or less distinct varieties of Peas were obtained from several seedsmen and subjected to a two year's trial. All the … varieties yielded perfectly constant and similar offspring; at any rate, no essential difference was observed during two trial years. For fertilization 22 of these were selected and cultivated during the whole period of the experiments. They remained constant without any exception.”http://www.mendelweb.org/CollText/homepage.htmlMCB140, 29-08-07 3“Pure-breeding line”An awkward phrase that is best retired, but never will be.It refers to an organism that exhibits a particular trait (e.g., seed color), and all progeny of that organism (whether it is selfed, or outcrossed to another such organism) also exhibit that trait.Pure-breeding lines are best made by selfing, or brother-sister crosses (like Nefertiti).MCB140, 29-08-07 4“An SCN9A channelopathy causes congenital inability to experience pain” Nature Dec. 14, 2006“The index case for the present study was a ten-year-old child, well known to the medical service after regularly performing 'street theatre'. He placed knives through his arms and walked on burning coals, but experienced no pain. He died before being seen on his fourteenth birthday, after jumping off a house roof.”MCB140, 29-08-07 5William Ernest Castle – founder of mouse genetics (UCB 1936-1962)1. Inbreeding as a tool for making genetically uniform strains of mice that are homozygous for every allele in the genome.2. Brother-sister matings – makes 12.5% of all loci in the genome homozygous (Clarence Little).Why? – homework!!After 40 generations of brother-sister mating, >99.98% of genome is homozygous. By F60, mice are considered genetically identical to one another.MCB140, 29-08-07 6Mendel picked the pea as the system.What traits to pick?“Experiments which in previous years were made with ornamental plants have already provided evidence that the hybrids, as a rule, are not exactly intermediate between the parental species. With some of the more striking characters, those, for instance, which relate to the form and size of the leaves, the pubescence of the several parts, etc., the intermediate, indeed, is nearly always to be seen; in other cases, however, one of the two parental characters is so preponderant that it is difficult, or quite impossible, to detect the other in the hybrid.”http://www.mendelweb.org/CollText/homepage.htmlMCB140, 29-08-07 7MCB140, 29-08-07 8The reaffirmation of a known phenomenonMendel is pointing out the distinction between two “types” of traits.1. The hybrid plant is “intermediate” in phenotype between two parents. For instance, the offspring of a tall and a short plant would be intermediate in height.2. The hybrid plant has the phenotype like one of the parents. For instance a green x yellow cross yields only yellow-seeded plants.Mendel chose to study “type 2 traits” – a judicious decision. We now know that the laws he discovered in doing so also apply to “type 1” traits, but that fact is considerably more difficult to observe.MCB140, 29-08-07 9yellow greenQualitative (“simple”) traitaaAAMCB140, 29-08-07 10short tallQuantitative (“complex”) traitAAaaMCB140, 29-08-07 11Not Mendel’s faultIn retrospect, we see that the overwhelming majority of traits in humans, other animals, and plants – traits that are of most interest and importance from a public health, and other societally relevant perspectives (height, weight, body plan, facial appearance, skin color) – are quantitative. Mendel – wisely – chose to study a set of “qualitative” traits because he was a skilled reductionist. As a consequence, he discovered two fundamental facts about the functioning of the genetic material. The teaching of genetics, however, always begins with Mendel’s work, and this creates two erroneous impressions:1. … that the traits he studied are “controlled by a single gene.” That, of course, is not true (all traits are controlled by multiple genes) – he simply worked with plants that were genetically different from each at only one locus out of the many required for the development of the trait. We shall return to that point shortly.2. … that simple Mendelian relationships of recessivity and dominance between alleles, and “one gene-one trait” correlations he – supposedly – observed are ubiquitous in Nature. “She has her mother’s eyes.” “He gets his brains from his Dad.” Neither trait – eye color nor “intelligence” – exhibit simple Mendelian inheritance, yet most people assume otherwise.MCB140, 29-08-07 12The genesis of the famous term“… in other cases, however, one of the two parental characters is so preponderant that it is difficult, or quite impossible, to detect the other in the hybrid.This is precisely the case with the Pea hybrids. In the case of each of the 7 crosses the hybrid-character resembles that of one of the parental forms so closely that the other either escapes observation
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