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Berkeley MCELLBI 140 - Lecture Notes

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1MCB140 01-31-07 1BridgesMullerMorganSturtevantThe Fly Room, Columbia University ca. 1919MCB140 01-31-07 2MCB140 01-31-07 3Correlation between cytological and genetic phenomena as a discovery tool1. Boveri (1880) – nuclear transplantation in sea urchins; early development in triploid sea urchins.2. Sutton (1900) – chromosome dynamics in grasshoppers and Mendel’s laws (note: strictly speaking, Sutton should have looked at chromosome dynamics in the pea, Pisum sativum, but whatEVERRR).3. Morgan (1910) – correlation between the inheritance of white and the sex chromosomes.4. Bridges (1915) – “the exceptional female,” nondisjunction, and firm evidence for the chromosome “theory” of inheritance.5. McClintock, Stern (1930) – creation of novel genotypes by meiosis via homologous recombination correlates with creation of novel karyotypes via crossingover between nonsister homologs.MCB140 01-31-07 4Criss-cross inheritance: white-eyed sons and red-eyed daughters of white-eyed mothers and red-eyed fathers2MCB140 01-31-07 5Calvin Bridges… “raised by his grandparents in upstate New York, both of his parents dying young. He was a talented student buit his grandparents were poor and Bridges had to make do with clothing that was constantly mended. He was too ashamed to go to social activities in high school because of his ragged appearance. He received a scholarship to attend Columbia University, but he had to support himself with part-time work. Bridges took the same introductory biology course as Sturtevant, and Morgan, who learned of Bridges’ circumstances, asked him to be a part-time bottle-washer and food preparator for the fly work that was gaining momentum in Morgan’s laboratory.” Carlson Mendel’s LegacyMCB140 01-31-07 6vermilion“… Bridges’ circumstances changed approximately a year after he began working for Morgan. He showed Morgan a bottle that contained a fly whose eye color seemed to be brighter than usual. Morgan isolated the fly, showed that it carried another X-linked trait, and called that trait vermilion. He also assigned Bridges to a desk and told him to look for more mutations.”MCB140 01-31-07 7(A) Bridges (left) and Sturtevant in 1920. (B) Morgan in 1917. The photo of Morgan, who was camera shy, was taken by Sturtevant using a camera hidden in an incubator and operated remotely by means of a string. The books and microscope in the background were at Sturtevant's desk G. Rubin and E. Lewis Science 287: 2216.MCB140 01-31-07 8Required readingEverything to do with Fig. 5.21.Pp. 149-154 of Ch. VI in Morgan et al The Mechanism of Mendelian HeredityProblems 4.32 and 4.34Everything to do with Fig. 14.32.3MCB140 01-31-07 9The “exceptional female” appearsMCB140 01-31-07 10MCB140 01-31-07 11Fig. 13.28MCB140 01-31-07 12Fig. 4.21How could a white-eyed mother have a white-eyed daughter?Note:An XXY Drosophila is female.An XXY human is male.Y?Stay tuned for Prof. Cline’s lecture.4MCB140 01-31-07 13 MCB140 01-31-07 14MCB140 01-31-07 15 MCB140 01-31-07 165MCB140 01-31-07 17 MCB140 01-31-07 18MCB140 01-31-07 19Normal femaleWhite-eyed daughtersof an “exceptional” motherMCB140 01-31-07 206MCB140 01-31-07 21Bridges, C. B. 1935. Salivary chromosome maps with a key to the banding of the chromosomes of Drosophila melanogaster. J. Hered. 26: 60–64MCB140 01-31-07 22MCB140 01-31-07 23 MCB140 01-31-07 24Fine, fine, genes are on chromosomes. Now what?The next two major advances in genetics both came from the study of apparent exceptions to Mendel’s laws.#1. Strong deviations from a 1:1:1:1 phenotyping ratio in a AaBb x aabb cross Æ “coupling and repulsion” Ælinkage Æ genetic map#2. Highly aberrant phenotypic ratios (e.g., 9:3:4) when – for example – brother-sister mating black Labrador retrievers fathered by a black Dad and yellow Mom Æ epistasis7MCB140 01-31-07 25Hmmmmm“It was not long from the time that Mendel's work was rediscovered that new anomalous ratio began appearing. One such experiment was performed by Bateson and Punnett with sweet peas. They performed a typical dihybrid cross between one pure line with purple flowers and long pollen grains and a second pure line with red flowers and round pollen grains. Because they knew that purple flowers and long pollen grains were both dominant, they expected a typical 9:3:3:1 ratio when the F1 plants were crossed. The table shows the ratios that they observed. Specifically, the two parental classes, purple, long and red, round, were overrepresented in the progeny.”http://www.ndsu.edu/instruct/mcclean/plsc431/linkage/linkage1.htmMCB140 01-31-07 26381 381 Total 24 55 Red, round (ppll) 71 21 Red, long (ppL_) 71 21 Purple, round (P_ll) 215 284 Purple, long (P_L_) Expected Observed http://www.ndsu.edu/instruct/mcclean/plsc431/linkage/linkage1.htm“Coupling” and “repulsion”MCB140 01-31-07 27 MCB140 01-31-07 28Two separate issues1. How do we know there’s a problem? Is this really a deviation from 9:3:3:1, or should they look at more seeds?2. If there really is a deviation, how can one explain it?8MCB140 01-31-07 29GINA, aGAINNature Genetics - 39, 133 (2007) Legislation to prevent genetic discrimination in employment and insurance decisions is essential so that individuals can make use of existing genetic tests to manage their own health decisions. This legislation is also imperative to protect those who volunteer for genetic research that will benefit others affected by common diseases.MCB140 01-31-07 30The Genetic Information Nondiscrimination Act (GINA), legislation to prevent the use of genetic information in employment and insurance decisions, has been introduced six times in various forms to the US Congress over the last 12 years and has been unanimously passed twice by the US Senate, but not by the House of Representatives.Proponents of the Act have a fresh opportunity with the newly elected 110th Congress. GINA. The legislation is essential if human genetic research is to continue with full public support and deliver the anticipated health benefits that underpin much of its funding. Most crucially, the human genome belongs to the whole human race, leading to the essential "principle of genetic solidarity and altruism" so aptly described by the UKHuman Genetics Commission in their 2002 report on the use of personal genetic data, entitled "Inside Information" (http://www.hgc.gov.uk). In essence, 'I get myself tested so that my results may help another affected by my disease or


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Berkeley MCELLBI 140 - Lecture Notes

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