Reading pp152 154 Mitotic recombination can produce genetic mosaics and cause cancer I ve asked to reserve a lecture room from 7 9pm Thursday April 5 for a review session in connection with the midterm on Monday April 9 I ll announce where the session will be held as soon as I know myself Last Friday 1 genetically sensitize the system turn lof recessives into dominants but only with respect to one non essential aspect of their function Poising the activity level of your favorite gene on a phenotypic threshold to make other genes haploinsufficient but only with respect to the functioning of your favorite gene So that 1 we can identify new mutations of interest in the F1 generation first generation after mutagenizing the parents AND 2 can overcome some complications of pleiotropy so that we can more easily study the non vital aspects of the functioning of genes that ALSO have vital functions 1 genetically sensitize the system turn lof recessives into dominants but only with respect to one non essential aspect of their function Based on the rationale that Wildtype fly must normally have an excess of most genes activity as insurance against fluctuations in the levels of activity of various genes in a pathway during development if take away that cushion for any one gene in a pathway now make the normal operation of the pathway with respect to that one gene more vulnerable to reductions in other gene levels Another way around the limitations of pleiotropy in genetic screens 2 use targetted genetic mosaics to screen for recessives in the F1 homozygous clones in heterozygotes in non essential tissues only recover new recessives in the F1 without making them dominant genetic mosaics according to your text an organism containing tissues of different genotypes cells all derived from a single initial cell zygote genetic mosaic vs organism genetic chimera an embryo or animal composed of cells from two or more different organisms individuals and that s what they say in the text genetic mosaics are extremely useful for determining where a particular gene s function is needed Your text short changes the key concept of cell autonomy in gene function Fig 20 4 genetic genetic mosaics mosaics are extremely useful for determining where a particular gene s function is needed nonmosaic wildtype L2 L1 L2 L1 differentiation non mosaic ag mutant L2 L1 L2 phenotypic effect of ag vs ag L1 In what cell type L2 vs L1 is ag function needed to elicit normal differentiation of L1 Where is ag needed mosaic white marks ag nonmosaic wildtype ag ag mosaic L2 L1 L2 L1 L2 L1 L2 L1 L2 L1 L2 L1 L2 L1 ag non mosaic ag mutant L2 L1 ag L1 differentiates abnormally despite being ag L1 differentiates normally despite being ag ag seems to work in L2 to signal L1 like boss For ag the cell whose phenotype is mutant is not the cell whose genotype is mutant Hence ag is not cell autonomous with respect to the L1 phenotype The genetic marker is cell autonomous that s why it was chosen since the cell whose marker phenotype is mutant is the cell whose marker genotype is mutant if a cell s genotype in the mosaic dictates that cell s phenotype nonmosaic wildtype L2 L1 L2 L1 L2 L1 L2 L1 L2 L1 L2 L1 L2 L1 L2 L1 ag non mosaic ag mutant ag is nonautonomous ag ag ag ag ag ag seems to work in L2 to signal L1 When discussing autonomy nonautonomy need to specify the phenotype in question ag is non autonomous with respect to the L1 differentiation phenotype perhaps ag is autonomous with respect to generating the signal in L2 if we had an assay for the signal we might see that phenotype directly T H Morgan published on genetic mosaics in 1914 do males normally have white eyes first nuclear division of a zygote Hence 50 w vs w too large for our purposes w w XX w XO XO XX otherwise diploid AA Fig 14 33 Another way around the limitations of pleiotropy in genetic screens 2 use genetic mosaics to screen for recessives in the F1 look for homozygous mutant clones in otherwise heterozygous animals identify and recover new recessives in the F1 even works for new mutants that are recessive lethal or sterile provided one generates clones in only a small fraction of all cells or one generates clones only in non essential tissues Another way around the limitations of pleiotropy in genetic screens 2 use genetic mosaics to screen for recessives in the F1 look for homozygous mutant clones in otherwise heterozygous animals Based on a phenominon discovered 30s by former chair of U C Zoology Dept mitotic recombination but improved upon enormously in modern times only possible because of a very strange aspect of fly chromosome behavior homologous chromosomes pair during mitotic interphase Stern s observation for fly heterozygous for recessive cell autonomous l o f alleles of two genes yellow body singed bristles yellow body singed bristles If irradiated ionizing during development occasionally saw odd ADULT fly deduced mistake in mitosis not new mutant alleles most flies wildtype patch of y y patch of sn sn twin spot Fig 5 23 p152 Consider what it is about mitosis that insures daughter cells will have the same genotype as their mother cell XmXp y sn y sn y sn y sn m y sny sn p then if instead y sn y sny sn y sn yy m m y sny sn p p m p m p sn sn m m p p y sn y sn m y sn y sn m p p What if DNA breaks and improper repair after S phase change relationship between genes and centromeres y sn y sn m p y sn y sn y sny sn m m mistake y sn y sn m m m m p p y sn y sn yellow y sn y sn m y sny sn m NO CHANGE if instead twin spot singed p p p p DNA breaks and improper repair after S phase generate the twin spot of cells homozygous for y and sn y sn m y sn p y sn y sn y sny sn twin spot because progeny of the y y sn sn original cells tend to stay together ADULT EXTERIOR size of patches depends on when abberrant mitosis occurs m m mistake p p y sn y sny sn y snGrowth m m m m p p m y y yellow y sn y sn patch clone of sn sn singed y sny sn m patch clone of p p Fig 5 24 p152 What if we had induced a NEW recessive MUTATION on a mutagenized y sn chromosome in the father s sperm that affected cell growth parameters appearance of an ABNORMAL homozygous yellow patch next to homozygous singed patch would SIGNAL that the female carried a new mutant allele y m sn m y m sn y m sn y m sn y m sny m sn p m m mistake p p y m sn …
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