Two loci long chrom long chrom short chrom Parent A short chrom AA AA x BB BB A A Parent B A A Two loci incomplete dominance new and improved B B B B locus 2 locus 1 locus 2 AB AB F1 locus 1 Locus1 Locus 2 AB AB x AB AB 16 possibilities F2 NO progeny as extreme as diploid hybrid 2 locus interaction For example locus 2 is polymorphism in a transcription factor gene that affects protein binding affinity locus 1 is in a binding site Effect of J at locus 2 Effect of variation at locus 2 depends on genotype at locus 1 non additive Different in sequence Lab parent Pathogenic parent Lab Pathogenic Tested in hybrid diploids Lab Pathogenic NO progeny as extreme as diploid hybrid Diploid hybrid 1 One mutant gene From pathogenic strain One mutant gene From pathogenic strain From lab strain Two mutant genes Two mutant genes From pathogenic strain From pathogenic strain From lab strain From lab strain Two mutant genes Three mutant genes From lab strain From pathogenic strain From lab strain Again diploid with this gene from the pathogenic strain grows BETTER at high T From pathogenic strain Diploid with this gene from the pathogenic strain grows WORSE at high T 2 Three mutant genes From pathogenic strain From pathogenic strain Three mutant genes From pathogenic strain From pathogenic strain Three mutant genes From pathogenic strain From pathogenic strain Three mutant genes in same locus From pathogenic strain From pathogenic strain From pathogenic strain Alleles from the same strain at different genes loci can have different effects Three mutant genes in same locus Three mutant genes So why did 0 900 haploid progeny have a phenotype as extreme as the diploid hybrid 3 NO progeny as extreme as diploid hybrid Lab parent Pathogenic parent Diploid hybrid NO progeny as extreme as diploid hybrid Lab parent Linked mutations of opposite effect Pathogenic parent Diploid hybrid Linked mutations of opposite effect Path Path Lab Linked mutations of opposite effect Path Lab Very unlikely Multiple linked loci 4 Model organism to human Why pigmentation Golden mutation Camouflage Sexual selection Protection from UV Controlling light scatter Sunlight for vitamin D Accident something else selected for nearby Golden mutation Melanosomes melanin producing organelles Golden mutation Golden mutation 1981 original mutant arose spontaneously in the lab 1981 original mutant arose spontaneously in the lab Showed mendelian segregation 1 locus and is recessive Showed mendelian segregation 1 locus and is recessive Dramatic single locus differences not common in the wild Why not 5 Linkage analysis with sparse markers mapped golden to markers on chromosome 18 but highresolution position of markers unknown Linkage analysis with sparse markers mapped golden to markers on chromosome 18 but highresolution position of markers unknown Genome sequence not completed Library screen Linkage analysis with sparse markers mapped golden to markers on chromosome 18 but highresolution position of markers unknown Shear ligate Genome sequence not completed Hybrid cell lines not available Native WT chromosomes Library screen Shear ligate Native WT chromosomes Library screen Shear ligate Genomic library Native WT chromosomes Genomic library Hybridize to marker oligo 85 kb DNA containing chr 18 marker 6 Fine mapping 85 kb Fine mapping 85 kb Inject into golden larvae Inject into golden larvae Fine mapping Fine mapping WT uninjected Golden uninjected Golden uninjected 85 kb 85 kb Inject into golden larvae Inject into golden larvae Fine mapping Fine mapping 85 kb WT uninjected Golden uninjected 85 kb Inject into golden larvae mosaic rescue 7 Fine mapping Fine mapping 85 kb 85 kb slc24a5 mRNA slc24a5 mRNA Inject into golden larvae Fine mapping Gene is strongly conserved WT uninjected Looks like a Na Ca exchange pump Golden uninjected Inject into golden larvae Gene is strongly conserved Looks like a Na Ca exchange pump Gene is strongly conserved Looks like a Na Ca exchange pump premature stop codon in DNA of golden embryos 8 Gene is strongly conserved Looks like a Na Ca exchange pump Human can rescue fish Human mRNA injected premature stop codon in DNA of golden embryos Don t usually see such dramatic mutations in the wild Human can rescue fish What is this gene slc24a5 melanophore cell marker Golden uninjected WT Human mRNA injected gol Fish mRNA injected What is this gene What is this gene melanophore cell marker cell line slc24a5 QPCR WT in mouse Cells themselves are present gol 9 What is this gene melanosome organelle What is this gene melanosome organelle slc24a5 Importance in humans No truncation in humans but No truncation in humans but No truncation in humans but Which is the ancestral and which the derived allele No other species have the Thr allele what does this mean 10 No truncation in humans but No truncation in humans but No other species have the Thr allele what does this mean Could be deleterious just an accidental mutation No other species have the Thr allele what does this mean Could be deleterious just an accidental mutation Could be advantageous for some humans no other species Population genetics Survey multiple European Americans in Utah 99 Thr Population genetics Survey multiple European Americans in Utah 99 Thr Survey multiple Han Chinese in Beijing 93 Ala Survey multiple Japanese in Tokyo 93 Ala Survey multiple Yoruba in Ibadan Nigeria 93 Ala Population genetics Population genetics Survey multiple European Americans in Utah 99 Thr Survey multiple European Americans in Utah 99 Thr Survey multiple Han Chinese in Beijing 93 Ala Survey multiple Han Chinese in Beijing 93 Ala Survey multiple Japanese in Tokyo 93 Ala Survey multiple Japanese in Tokyo 93 Ala Survey multiple Yoruba in Ibadan Nigeria 93 Ala Survey multiple Yoruba in Ibadan Nigeria 93 Ala So this allele is NOT definining race So this allele is NOT definining race Does it explain differences in skin color in humans 11 Correlates with human differences Correlates with human differences AA 105 African Carribeans and 203 AfricanAmericans agreed to be genotyped and have melanin content measured 105 African Carribeans and 203 AfricanAmericans agreed to be genotyped and have melanin content measured Thr AG Thr Ala GG Ala Correlates with human differences Allele is rare 105 African Carribeans and 203 AfricanAmericans agreed to be genotyped and have melanin content measured Allele is rare AA AA Thr AG Thr AG Thr Ala GG Ala Correlates with human differences Allele is rare
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