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Lecture 6

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University of Toronto St. George
Human Biology
William Ju

TRENDS IN HEALTH AND DISEASElec6Genetic sequencing is used to understand how genes control health and disease by reading nts to sequence different organismal genomesCan now sequence whole genomes and exomes not include introns to see relatedness between sequence of different organisms ie homologues of gene sequences model organismsModel organisms are cheap convenient and easy to find and can be used to compare to other organisms Include C elegans zebra fish drosophila and mice C elegans nematode worm has 959 cells after apoptosis of 131 cells very small transparent so easily transported and cell lineage dendrogram created to follow apoptosis eventsExists as both male and hermaphrodite sensitive to UV light that can be frozen and thawed to resume functionLife cycle of 50 hours Dauer bypass of 1 developmental stage where it skips L3 to go to L4 with a life span of 3days after adulthood Contains 6 chromosomes with a 100Mb genome of 19000 genes 5000 essential for survival reproduction etc 14 types of chemosensory neurons which are similar to human GPCRs to detect chemicals4050 of genes have human homologues ie mutant diseased phenotype can be rescued using human genes since human and worm genes may be swappedCell death is programmed into cell lineage which allowed identification of regulatory proteins of apoptosis in vertebratesC elegansCed9 regulator inhibits PCD by blocking Ced4 adaptoroverexpression Ced3 effectorcell deathHumansBcl2 regulator inhibits PCD by blocking Apaf1 adaptorCasp9 effectoroverexpression Casp3 effectordeathRas pathway is abnormally activated in C elegans to cause vulvaless mutationhuman cancersLIN3signal similar to EGF is normally secreted for anchor cell to form vulva binds to Let23 receptor EGF receptor then to Sem5 then Let60 Ras then Lin45 RafNormally causes differentiation and proliferation of these cells
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