Gene Evolution and Genetic Variation!Objectives!1) Definition and structure of a gene!2) Forces of gene evolution!3) Genetic variation!4) Human genetic variation!5) Medical relevance!!1)!Gene= unit of hereditary!•Promoter+ regions that influence promoter + stop codon!•!2)!New genes= generated from existing genes!•Intragenic mutation!◦Gene duplication, can mutate away from each other (divergence) -> paralogs!◦Multiple can generate families of related genes (ex. globin family)!‣DNA segment/exon shuffling!◦can generate new genes or many domains in the same gene!‣Ex. Alu!‣Two genes exchanges exons thru chrom. crossover-> 2 completely new genes!‣Above 2- during meosis: chromosomal crossover or non-disjunction of whole chromosomes!◦Horizontal transfer!◦Transposition!•When mobile genetic elements move from one chrom. site to another. Can jump w/o homolog. ◦recomb. !About 8% of our genome is actually mobile!◦Leads to genetic diversity!!◦DNA transposons (Class 2)!◦Cut and paste, donor doesn't stay!‣Retrotransposition (Class 1)!◦Copy and paste, donor stays, req. transcriptase to move via RNA intermediate!‣!4)!Human genetic variation, 0.4% difference in bp between people-> we're all mutants!!•Most common variant= WILDTYPE!•Minor variant >1%: POLYMORPHISM!•Variation assoc. with disease= MUTATION!•DNA level- diffs in nucleotide seq.!•Chromatin level- epigenetic changes!•!3)!Genetic variation!•Small- single bp changes!◦Pt. mutation- single bp change!‣Silent- no affect on aa seq.!•Missense- change in 1 aa!•Nonsense- change in aa to stop codon!•SNP= single nucleotide polymorphism!‣High frequency, 1/800, most are 1 of 2 alleles, linked with common complex conditions !•Medium!◦insertions and deletions!‣Often lead to frameshift mutations (unless insertion or deletion is a multiple of 3)!•Ex. Cystic Fibrosis: single codon deletion (even though in frame), autosomal recessive, •doesn't get to plasma membrane to perform function of Cl channel protein!variable number tandem repeats (VNTRs)!‣DIFF. from CNVs. Very short piece of DNA repeated over and over in a single stretch due •to replication error, meiotic recomb. events.!Unstable, prone to variation, mostly in "junk" DNA, some in genes -> diseases!•Tri-Nucleotide Repeat diseases (non-functional protein as the repeat got bigger and ◦bigger)!DNA fingerprinting, paternity determinationn!•copy number variations (CNVs)- DNA segment with copy # diffs in comparison between 2 or ‣more genomes!Piece of DNA with a unique sequence, you should have it twice in your autosomes. Very •frequent. Determine genetic relations between people. !Varies due to deletions, duplications, inversions, translocations!•Large- structural rearrangements by genetic recombination!◦HR= Homologous recombination!‣Recomb. between homolog. chroms!•NHEJ= Non-homologous end joining!‣Recomb. between non-homolog. chroms!•Both of these are used by the cell for DNA repair!‣Good-> genetic diversity and variation, recombinant gametes!‣Bad-> translocations between nonhomolog. chroms can lead to cancer, disease, cell death!‣Homologous recombination
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