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University of Toronto St. George
Human Biology
Stephen Wright

LECTURE 22 Final Exam: April 12 from 2-4pm Both sections 20-25% based on first semester Rest based on second semester Tutorial Quiz – epigenetics and genetics o Look over calculations for odds ratios and lod ratios o Quantitative genetics calculations Regulated gene expression All start with same types of cells, stem cells, containing same amount of genes, DNA Genes regulated by other factors and proteins within genome Model organisms used to study development o Zebrafish o Nematode c elegans o Arabidopsis o Mouse o Fruit flies o Used to Small size so easily manipulated Look at flies and mice to drive development in humans • Pathways and genetic mechanisms conserved • What occurs in flies, occur in humans • Genomes sequenced so can find genes with mutant phenotypes All living forms are related Fly Loss of function of eyeless gene in drosophila = > no eye or small eye forming Pax-6 gene is homolog of eyeless Analog in humans called Aniridia MUTATIONS o No functional copies of aniridia eyes – embryos have no eye formation, lethality in utero Homozygous loss of function leads to embryonic lethality o Heterozygote – lack one or two irises One wildtype only Knockout – reverse genetics To see what genes are important in what pathways? What defects result? Genes important for what? Forward genetics…mutagenize model organisms o Cross mutant mice with wildtype mice to perform phenotypic analysis Drosophila so important o Best genetic model organism THUS best model to study function of genes in development o Embryo to adult = 10-11 days at 23 degrees C o Genes positioning relationship btw axis conserved among species Correct formation of axises in embryo lead to normal adult fly 1995 – Nobel prize for discoveries concerning early development of drosophila embryos Found the genes controlling axis and that they were conserved Different classes of drosohpila genes important for patterning of embryo Anterior posterior pattern development focused today o First class is maternal effect genes Maternal effect mRNAs deposited in early embryo by mother These genes direct formation of anterior, posterior axis in fly Genotype of mother important • If mother has at least one wildtype copy of maternal effect gene, then will have functional maternal affect protein • If lack protein, then embryo will lack functional maternal affect protein, resulting in mutant embryo • Father does not matter – true for many species, including humans • Mother’s genes that set up axis o Must have at least one wildtype copy in order to have normal maternal affect proteins Present in concentration gradient • Bicoid = maternal effect gene, deposited and localized to anterior portion of drosophila embryo • Gradient o Embryo synsinitia Nuclear division without cytoplasmic division One embryo has many nuclei, but not cellular division So easy for RNAs deposited to diffuse from one end to other If bicoid at anterior end, see gradient of expression from antieror to posterior Very little expression when get past embryo Embryos lacking bicoid protein because mother had no functional copies of gene • If responsible for antieror position then embryos lack antieor portion Second, third, and fourth types are zygotic genes • Encode zygotically active proteins responsible for segmentation seen within embryo • Second class are gap genes o Affect formation of continous segment in embryo o Lack expression – see broad regions of embryo or larva being deleted o Kruppel Expressed in yellow, without it then result in short lethal embryo Third class called pair rule class • Act at double segment • Present at specific position in each pair of segments • The final embryo and la
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