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Lecture #7 Notes taken on the voice recording of the lecture. includes figures from slides with accompanying text for clarity.

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York University
BIOL 4285
Michael Scheid

Lecture 7 Genetic MappingAlzheimers March 4 2011Last ClassMapping the genome producing physical maps sequence of genome How the sequence was derived by the consortiums Provided an architecture for finding new genesIf we have a gene we found on the map through homology we can now log into the database and do homology searches We can find the intronsexons based on the boundaries and clone that gene as a genomic sequence introns and exons or clone the mRNA and make cDNA from it to have just the ORFSometimes you dont have an enzyme or a protein just a diseaseSomeone has a disease and we want to know what the causative agent isIf it is multifactorial there are a lot of genes that contribute to the epidemiologyIf we have a disease the is segregating in a Mendelian segregation pattern either autosomal dominant autosomal recessive Xlinked mitochondrial then it is a single gene disorder mutation leading to disease phenotype ie Huntingtons Genetic Mapping of Mendelian CharactersDo this through linkage analysisLink the disease to a locus which is a region of the genome that is segregating with the disease through aMendelian genetic pattern usually autosomal recessivedominant or XlinkedClone the gene without knowing anything about it or what it is We are going to use recombination to find a disease causing gene when we only have a diseaseEvent that occurs during meiosis from one generation to the next that separates loci on chromosomesIf chromosomes never undergo recombination then we cannot do linkage analysis because everyones chromosomes would stay the same from generation to generationAs long as the frame is maintained there is no lossgain of genetic material and therefore no problemLoci on separate chromosomes segregate independentlyA and B on separate chromosomes will have independent assortmentLoci on the same chromosome segregate as a function of recombinationfrequencyOccurs more often when loci are far apart less often when loci are close togetherPedigree 131Out of 7 meiosis there are two recombinantsThis can give us some insights into the distance between A and BPretty far apart since there are 27 recombinantsIf there were no recombinants the distance would be smallWe have to know at least 3 generations called a phase in order to be able to use recombination as adistance tool Lecture 7 Genetic MappingAlzheimers March 4 2011RecombinationSingle crossover can have NR and RDouble crossovers all are NR because alleles are restored to original chromosomesSo the chance of recombination approaches 50 but cannot go overCannot say that two loci are so far apart that there will be 100 recombinationAs they get farther apart double recombination is more likely to occurThe closer the loci get the closer the RF gets to zeroFraction never goes over 05 fraction ratio of RNRRecombination fraction isDNA PolymorphismInvolves 2 loci A and BCan be genesCan be those STS sequence tag sites not genes but are unique sequences on the chromosomeAny polymorphismmarker that can be located on a chromosomeCan also be a disease phenotypeiethe phenotype and gene ACan have two phenotypes ie person with white hair gets this disease how often do they segregatePolymorphism trinucleotide repeats tandem repeats FLRP SNP VLTRAnything that can be mappedlocated on a chromosomeSingle nucleotide polymorphism SNP are the most useful for mapping genetic markers because there aremillions of them spread out in the human genomeWe need heterozygosity for mappingIf one is trying to link a disease and everyone in the population has the marker but there is only A1 or A2 that meansthe population has A1has A2In a family there may not be an informative meiosis because even if there is a crossover the same allele is crossing over and thus there is no visible change in phenotype or genotypeThe more heterozygozity the better the chance of knowing whether recombination has occurredGives potential for informative meiosisWhat type of markers are not useful for polymorphisms because there are not variables in the populationHistonesrRNAAny gene that is conserved in a populationWhat types of markers are great for polymorphisms heterozygositySingle nucleotide polymorphisms only one variable in the population not necessarily 5050Repeats VLTR TNR ie IT5Huntingtons gene heterozygozity in the number of repeatsDifficult to genotype and not nearly as frequent as SNPGives useful heterozygosity We lose the usefulness because there are not many of them Have to use micro array or PCR based assay
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