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2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
2008 PGSAS G-nomes
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2008 PGSAS G-nomes

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    • 1. The Human Genome Project <ul><li>June 26, 2000: Successful completion of the first ‘draft’ of the entire human genome!!! </li></ul><ul><li>The race between Celera and NIH is finished. The private company appears to have won. </li></ul>
    • 2. The Chicken Genome Project <ul><li>An initiative begun by NIH in 2002 </li></ul><ul><li>Completed in 2004 </li></ul><ul><li>Other species considered: </li></ul><ul><ul><li>Cats, cows, sheep, horses, dogs </li></ul></ul><ul><ul><ul><li>Cow begun in 2004 </li></ul></ul></ul><ul><ul><ul><li>Pig begun in 2005 </li></ul></ul></ul><ul><ul><ul><li>Who's next? </li></ul></ul></ul><ul><ul><li>Look here: Ensembl </li></ul></ul><ul><li>But, What the heck is a ‘genome’? What did they/we win? </li></ul>
    • 3. The Genome (?) <ul><li>G-nomes; Grumpy and Sleepy? </li></ul><ul><ul><li>With apologies to Dr. Dean Snow </li></ul></ul><ul><li>Not really. </li></ul><ul><li>A genome is a complete sequence of all the known genes of an organism; including their structure and function </li></ul>
    • 4. Maps and markers <ul><li>What’s a genetic map? </li></ul><ul><li>With apologies to Dr. David Bottstein. </li></ul>
    • 5. One kind of map of Penn State
    • 6. Here’s a better view
    • 7. Now I know this will be helpful
    • 8. Perhaps we need a different kind of map?
    • 9. How about this?
    • 10. Or, this?
    • 11. Or, even this?
    • 12. The Genome (among friends) <ul><li>Chromosomes </li></ul><ul><ul><li>Each chromosome is one molecule of DNA. </li></ul></ul><ul><ul><li>10 7 to 10 8 base pairs </li></ul></ul><ul><ul><li>A structural gene, coding for a polypeptide/protein, is between 10 3 to 10 4 bp. </li></ul></ul><ul><ul><li>Approximately 10% of the genome is coding. </li></ul></ul><ul><li>DO THE MATH!! </li></ul><ul><ul><li>A chromosome contains 1,000 to 10,000 genes. </li></ul></ul><ul><ul><li>Vertebrate genomes contain approximately 50,000 to 100,000 genes. </li></ul></ul><ul><li>These are generalizations and are highly species specific. </li></ul><ul><li>Indeed, calculations from the human genome project suggest that there are approx. 35,000 genes </li></ul>
    • 13. Genes and Markers and Maps <ul><li>Gene Mapping </li></ul><ul><ul><li>The location of genes to specific positions (e.g., loci) on specific chromosomes. </li></ul></ul>
    • 14. Structural Genes <ul><li>Consider Hemoglobin! </li></ul><ul><li>Normal adult hemoglobin consists of 2 molecules each of 2 different polypeptides. </li></ul><ul><ul><li>α (141 aa) and β (146 aa) </li></ul></ul><ul><ul><li>On chromosomes 16 and 11 </li></ul></ul><ul><li>Given 3 bp per aa </li></ul><ul><ul><li>the β chain has 4 438 possible single bp variants </li></ul></ul><ul><ul><li>This number exceeds the total number of fundamental particles in the universe. </li></ul></ul>
    • 15. Hemoglobin- β mutations <ul><li>Non-sense </li></ul><ul><li>Nil-STOP </li></ul><ul><li>UAG </li></ul><ul><li>ATC </li></ul><ul><li>Mutant </li></ul><ul><li>Mis-sense </li></ul><ul><li>Valine </li></ul><ul><li>GUG </li></ul><ul><li>CAC </li></ul><ul><li>Mutant </li></ul><ul><li>Same-sense </li></ul><ul><li>Glutamate </li></ul><ul><li>GAA </li></ul><ul><li>CTT </li></ul><ul><li>Mutant </li></ul><ul><li>Wild-type </li></ul><ul><li>Glutamate </li></ul><ul><li>GAG </li></ul><ul><li>CTC </li></ul><ul><li>Normal </li></ul><ul><li>Type </li></ul><ul><li>Amino Acid </li></ul><ul><li>mRNA codon </li></ul><ul><li>DNA codon </li></ul><ul><li>Allele </li></ul>
    • 16. Mapping <ul><li>Prior to the 1980’s all mapping was accomplished using major genes of obvious phenotypic effect. </li></ul><ul><li>The advent of RFLP’s, AFLP’s, microsatellites and other molecular markers, we can identify large numbers of segregating loci, simultaneously in the same cross. </li></ul><ul><li>Remember that these markers are not true genes and are really ‘framework maps’, since they provide the ‘road map’ to locate genes of interest. </li></ul><ul><ul><li>Useful for locating and studying QTL / MAS. </li></ul></ul><ul><ul><li>Invaluable to investigating genomic organization across related species/genera. </li></ul></ul>
    • 17.  
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    • 24. Gene Order and Arrangements <ul><li>Now that we’ve talked about structure and function … </li></ul><ul><li>How do we figure out their placement on the map? </li></ul><ul><li>We take advantage of a violation of the law. </li></ul><ul><li>Specifically, Mendel’s law of independent assortment . </li></ul>
    • 25. Consequences of crossing over (1) Chiasma A B A B A B a b a b a b
    • 26. Linkage between a mutant gene and a marker Meiosis Mutant gene DNA marker Wild-type gene Variant DNA marker
    • 27. Consequences of crossing over (2a)
    • 28. Consequences of crossing over (2b)
    • 29. Chiasma frequency and distance between loci
    • 30. Using the test-cross <ul><li>135 </li></ul><ul><li>Total </li></ul><ul><li>3 </li></ul><ul><li>aB </li></ul><ul><li>aaBb </li></ul><ul><li>aB </li></ul><ul><li>4 </li></ul><ul><li>Ab </li></ul><ul><li>Aabb </li></ul><ul><li>Ab </li></ul><ul><li>Recombinants </li></ul><ul><li>60 </li></ul><ul><li>ab </li></ul><ul><li>Aabb </li></ul><ul><li>ab </li></ul><ul><li>68 </li></ul><ul><li>AB </li></ul><ul><li>AaBb </li></ul><ul><li>AB </li></ul><ul><li>Parentals </li></ul><ul><li>Number </li></ul><ul><li>Progeny Phenotype </li></ul><ul><li>Progeny Genotype </li></ul>
    • 31. Calculating Recombination Frequency <ul><ul><li>Number of ‘A’ individuals: </li></ul></ul><ul><ul><ul><li>68 + 4 = 72 </li></ul></ul></ul><ul><ul><li>Number of ‘a’ individuals: </li></ul></ul><ul><ul><ul><li>60 + 3 = 63 </li></ul></ul></ul><ul><ul><ul><ul><ul><li>χ 2 =0.6; ns </li></ul></ul></ul></ul></ul><ul><ul><li>Number of ‘B’ individuals: </li></ul></ul><ul><ul><ul><li>68 + 3 = 71 </li></ul></ul></ul><ul><ul><li>Number of ‘b’ individuals: </li></ul></ul><ul><ul><ul><li>60 + 4 = 64 </li></ul></ul></ul><ul><ul><ul><ul><ul><li>χ 2=0.37; ns. </li></ul></ul></ul></ul></ul><ul><li>RF = (4+3)/135 = 0.0518 or 5.18% </li></ul>
    • 32. What if you had 3 genes of interest? <ul><li>Start with an F 1 produced by 2 pureline parents (AABBCC x aabbcc). </li></ul><ul><li>Backcross the F 1 to the triple-recessive parent. </li></ul><ul><li>Check that all alleles are segregating in a 1:1 ratio in the backcross </li></ul><ul><ul><li>Altered segregation will give a poor estimate of RF%. </li></ul></ul><ul><ul><ul><li>differential survival </li></ul></ul></ul><ul><ul><ul><li>misclassification </li></ul></ul></ul>
    • 33. Here’s how to determine gene order <ul><li>400 </li></ul><ul><li>TOTAL </li></ul><ul><li>32 </li></ul><ul><li>aBc </li></ul><ul><li>24 </li></ul><ul><li>AbC </li></ul><ul><li>4 </li></ul><ul><li>7 </li></ul><ul><li>aBC </li></ul><ul><li>14 </li></ul><ul><li>Abc </li></ul><ul><li>3 </li></ul><ul><li>49 </li></ul><ul><li>abC </li></ul><ul><li>51 </li></ul><ul><li>ABc </li></ul><ul><li>2 </li></ul><ul><li>120 </li></ul><ul><li>abc </li></ul><ul><li>103 </li></ul><ul><li>ABC </li></ul><ul><li>1 </li></ul><ul><li>F 1 gametes </li></ul><ul><li>Number of progeny </li></ul><ul><li>Progeny phenotypes </li></ul><ul><li>Class </li></ul>
    • 34. Calculate RF% as before <ul><li>ALL χ 2 are non-significant. </li></ul><ul><li>A – B = (14+7+24+32)/400 = 0.1925 or 19.25% </li></ul><ul><li>A – C = (51+49+14+7)/400 = 0.3025 or 30.25% </li></ul><ul><li>B – C = (51+49+24+32)/400 = 0.3900 or 39.00% </li></ul>
    • 35. And the answer is: B A C Since B-C is the largest RF, genes B and C must be the furthest apart; while A is in between. 39.00% 19.25% 30.25%
    • 36. Genes and Markers and Maps <ul><li>Gene Mapping </li></ul><ul><ul><li>The location of genes to specific positions (e.g., loci) on specific chromosomes. </li></ul></ul><ul><li>Linkage </li></ul><ul><ul><li>Genes that are located on the same chromosome are ‘linked’. </li></ul></ul>
    • 37. The Human Map 1 263 Mb 17 92 Mb 21 50 Mb X 164 Mb

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