Sem Hist Gen
Sem Hist Gen GGG 291
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This 34 page Class Notes was uploaded by Kaylah Wiegand on Wednesday September 9, 2015. The Class Notes belongs to GGG 291 at University of California - Davis taught by Staff in Fall. Since its upload, it has received 24 views. For similar materials see /class/191966/ggg-291-university-of-california-davis in Genetics (Graduate Group) at University of California - Davis.
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Date Created: 09/09/15
Mendelian interpretation of Continuous Variation 0 n A 1 mam a H 5 mamqu unz 4quot n 1 r r n murrx L a miim 39 wralm Continuous vs Discontinuous Variation 39 CONTINUOUS Quantitative traits combined effect of l several genes bell curve distribution of phenotypic values ex height seed color variation milk yield in cows East 1916 Height category cm UCD dairy cows Continuous vs Discontinuous Variation DSCONTNUOUS Qualitative traits discreet l unitscategories Round or wrinkled ripe sands min or groan sud Inlanors l I l 1 Greeneryeuawuminepws ex drosophlla eye color rrf 39 quot I Purple or whlia punk Mendel s pea traits blood types lnnared nr punched ripe nods Ami or letminal nowars TWO SCHOOL OF THOUGHT Biometrics Mendellsm Darwin VS Pearson Bateson Galton Weldon Galton s Law of Regression In a population mating at random the progeny of a parent with an extreme value for a measurable phenotype will tend on average to have values nearer to the population mean than in the extreme parent this principle declares that the crossbreeding of parents need not diminish the purity oftheir germ cells or consequently the purity of their offspring Bateson The Biometricians Argument Mendelism continuous traits discontinuous traits one trait many genes environment one trait one gene complete dominance can t explain intermediate progeny given complete dominance factorial constancy gametic purity objected the idea of cumulative effect of genes a econ s contributions to Mendelism Carlson 1966 Genetic Nomenclature Allelomor phs later shortened To allele Haterzygote Homozygote 1 F1 F2 F3 CTC Single Comb Recognized that unusual cases could be explained by Mendelism if one granted that the fact that in the cross breds one character in appearance dominated to the exclusion ofthe other is not ofthe essence of Mendel39s discovery Blue Andalusian Bateson s Contributions to Mendelism Carlson 1966 o Recognized that height in humans must be controlled by several genes and also environmental influences o Inheritance of lethal aIIeIes as recessive traits o Attempted to explain permanent hybrids heterozygotes by sexlinked traits r A 1 r 7 w 1 7 7 IHVJg 7 H452 r viva L I S Lilli lhgf ct begins Use Lib Ltlgtiadl EL E LJ Darbishire Davenport Recognized the value of Johanssen gt statistical methods Emphasized difference N39Isson39Ehle between inherited and LOCK environmentally produced Casue variations EaSt genotype RA Emerson phenotype Fisher 1 Both reported cases in different plant systems where F2 was more variable than F1 interpreted this to be due to segregation of several genes Sturtevant 1965 A Mendelian Interpretation of Variation that is Apparenty Continuous 1910 Studied maize Found 2 independent yellow colors of endosperm 34 independent red colors of pericarp 2 colors in aleurone cells when both alleles are present the 2 colors gradually blend quot39 V Data showed the expected Mendelian ratios fortotal yellows to white 151 However ratio of light yellow to dark yellow is v v unclear as a gradation of 5 I shades is present Also found traits such as number of rows of kernels on a corn cab to display a continuous pattern Edward M East Studies on Size Inheritance in Nicotiana 1916 An Argument for applying Mendelian concepts To continuous Traits Mendelizing characters are probably due to the interactions of several genes and presumably every gene may exhibit several somatic effects yet no one doubts that the Mendelian notation describes the inheritance of such things as color accurately and concisely Yet many geneticists still wouldn t use Mendelian concepts to describe continuous traits East provides arguments in favor of applying Mendelian thought to quantitative traits Presents 8 conditions for applying a Mendelian approach to continuous traits 1 Crosses between individuals belonging to races which from long continued selffertilization or other close inbreeding approach a homozygous condition should give F1 populations comparable to the parental races in uniformity 2 In all cases where the parent individuals may reasonably be presumed to approach complete homozygosis F2 frequency distributions arising from extreme variants of the F1 population should be practically identical since in this case all F1 variation should be due to external conditions 3 The variability of the F2 population from such crosses should be much greater than that of the F1 population 4 When a sufficient number of F2 individuals are available the grandparental types should be recovered East s 8 conditions continues 5 In certain cases individuals should be produced in F2 that show a more extreme deviation than is found in the frequency distribution of either grandparent 6 Individuals from various points on the frequency curve of an F2 population should give F3 populations differing markedly in their modes and means 7 Individuals either from the same or from different points on the frequency curve of an F2 population should give F3 populations of diverse variabilities extending from that of the original parents to that of the F2 generation 8 In generations succeeding the F2 the variability of any family may be less but never greater than the variability ofthe population from which it came Ronald A Fisher s Contributions towards acceptance of Mendelian inheritance Created foundations of population genetics Made the assumption that continuous traits were determined by a large number of Mendelian factors which leads to a distribution of traits normal then calculated the correlations between elatives to be expected under Mendelian itance and found them to be in ith the Biometricians R A Fisher CONCLUSIONS Mendel s laws on heredity can be applied to continuous traits as shown by several researchers presented here Using statistical methods to analyze such traits can also be helpful in an applied manner ex breeding decisions etc Modern Knowledge on the Analysis of Continuous Variation Sophisticated software increase pop Size Vl despread DNA polymorphisms analysis Genetic linkage to DNA polymorphisms not actual ID of genes exception Mendelian factors involved in breast cancer QTL mapping quantitative trait locus stretches of DNA closely linked to quantitative traits D QTL by PCR AFLP QTL map comparing DNA SNP array human pig mouse cow a new and well developed branch of Physiology has been created To this study we may give the title Generics Bateson References AH Sturtevant 1965 A history of Genetics Chap 9 Carlson 1966 The gene a critical history Chap 2 The Fight to Legitimize Genetics East 1910 A Mendelian interQretation of variation that is apparentlv continuous American Naturalist 44 6582 East 1916 Studies on size inheritance in Nicotiana Genetics 1164 Sphtgenes By Andrew Webb GGG291 December 3 2008 GENE sou ENCE TGT Trc PHE ARG 7 N01 TRANSLATED Background 0 By 1970 s physical structure ofthe gene was firmly established 0 Based on bacterial experimentation The sequences of DNA RNA and protein were linearly analogous 0 Evidence suggested that eukaryotes behaved similarly 0 Bacterial gene structure believed to be universal Richard Roberts Phillip Sharp Worked with adenovirus 1 Philip Leder Worked on mice Eukaryote Background 0 Some evidence suggested that bacterial gene expression may not be universal 0 Physical separation of transcription and translation in eukaryotes 0 DNA content between various eukaryotes 39 Genome size 0 Presence of hnRNAs 0 Modified mRNAs 39 5 G Cap 39 PolyA Tail Methods Background 0 Restriction Endonucleases 0 Bacterial defense mechanism 0 Many different enzymes Each recognizes unique sequence 39 Cleaves at unique sequence EcoRI Escherichia coli RY13 539GAATTC339 539G AATTC339 339CTTAAG539 339CTTAA G539 Methods Background 0 RLoops RNADNA duplex RNADNA higher melting temperature than DNADNA when in high concentration of formamide RNA displaces second DNA strand creating loop 0 Visualized Via electron microscopy Adenovirus Chosen as an ideal system for the study of eukaryotic gene expression 0 Established restriction sites 2 Structural proteins were identified 2 dsDNAgenome o o o 39 DNA was translated by host RNA polymerase Abundance of nuclear and cytoplasmic RNA 39 Both forms could be easily collected for study In late stages of infection Long RNAs were transcribed 39 Stable cytoplasmic mRNAs were shorter than the transcribed NAs Both Phillip Sharp and Richard Roberts organism in the discovery of split genes Split Genes 0 Sharp 1977 0 Spliced segments at the 5 terminus of adenovirus 2 late mRNA Mapping the hexon polypeptide Purified by gel electrophoresis frorn adenovirus 2 infected cells 39 32 hours after infection PBS 188 lOOK Split Genes A F JillilElCl EcoRl G C B IJ D A HLE FK QLIJlll llledlll 0 Sharp 1977 0 Created duplex o lo 20 so 40 50 60 70 so 90 gt00 Puri ed hexon mRNA DNA fragments EcoRI Viral genome 39 Two Rloops found Expected Bound to two fragments 0 Tested again with HindIII One Rloop observed Expected Hexon is one fragment with HindIII Also observed singlestranded tails at both ends of the R loops Cap amp Tail of mRNA Tails were expected at 3 PolyA tail but not at the 5 Cap Hexon lOOK H Split Genes u A L I E J FJ D I LI 550m 6 C 5 id D A HLE FK 1 I J I L l I LIHmdm 39 Shan 1977 0 Intrigued by the singlestranded 539tail 39 Tested theory DNADNA duplexes were displacing the RNA Hexon mRNA was hybridized to HindIII ssDNA Tails still present 39 Theorized that tails might be due to palindromic sequences quot uranium x If true hairpins would form But no hairpins were formed 5 cu 3 Theorized that 539tails were from sequences transcribed further upstream If true RLoops would be observed near the 539tail in presence of EcoRI ssDNA 39 The RNADNA duplexes showed three loops at the 539tail Split Genes 0 Sharp 1977 o Concluded that the 5 tail was likely three sequences spliced together Creation of the smaller mRNA from longer precursors 3th Genes Roberts 1977 o An amazing sequence arrangement at the 5 ends of adenovirus 2 mRNA 39 Similar experiment to Sharp Tested RNADNA duplexes Polysomal mRNA Studied numerous mRNAs 39 Found 539 tails Split Genes o Roberts 1977 0 Tested 5 Tails of hexon mRNA 39 With fragmented ssD NA probes 39 5 tails demonstrated a looped pattern Found three duplex regions were formed by the 5 tail Rloop sequences were found between these regions 39 Ran controls to con rm results Checked for repeated segments None found 0 Theorized that the three regions were juxtaposed for the creation of mRNA Split Genes 0 Sharp and Roberts 0 Found evidence of intervening sequences Introns in cells infected by adenovirus Roberts was unsure if RNA splicing was in all eukaryotes or unique to adenovirus There would need to be evidence in another organisms Split Genes 0 Le de r 1 9 7 7 Intervening sequences of DNA identified in the structural portion ofa mouse Bglobin gene 0 Similar experiment to Sharp and Roberts but using mouse model Restriction site abnormalities of Bglobin gene Hindlll 39 Cleaved genomic Bglobin gene Unable to cleave Bglobin mRNA Abnormal distance between sites in cloned gene 39 Pstl 232kb and Hincll 126kb 11kb apart larger than the Bglobin mRNA Split Genes o Leder 1977 0 Rloops structure of Bglobin gene 39 Expected that one large Rloop would be present 39 Found two Rloops adjacent to one another With double stranded loop inbetween 39 mRNA hybridized with two discontinuous regions of the genomic DNA Supported by testing RNA with ssDNA Tested with another nonallelic Bglobin gene Found similar Rloop structure 39 The unhybridized DNA loops were believed to be intervening sequences Split Genes o Leder s Research 0 Evidence of intervening sequences in mouse Bglobin genes 39 Provided evidence that split genes were present outside of adenovirus infected cells known a 1 z 1 s 5 s 1 GENE squNCE TGT Trc CYS PHE ARG 7 N01 39mANSLA rED Introns Post Discovery Research 0 Splice Sites Nucleotide sequences which specify the exonintron border GU For 539ExonIntron border AG For 339ExonIntron border If mutated can change exonintron structure 0 Spliceosome v Complex which directs RNA splicing Complex similar to ribosomes Protein and RNA components Small nuclear RNA snRNA U1 U2 U4 U5 U6 Creation of lariatRNA o SelfSplicing r The ability for RNA to catalyze its own splicing Two types Group 1 and Group 2 Groups identified by differences in splicing mechanism Alternative Splicing 0 Observation that genes can be spliced into many different intronexon combinations Re search suggests that one in every twenty genes may be alternatively spliced Fibronectin o o TransSplicing Exons from different loci even chromo some 5
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