• Save
2008 PGSAS G-nomes
Upcoming SlideShare
Loading in...5
×
 

2008 PGSAS G-nomes

on

  • 944 views

 

Statistics

Views

Total Views
944
Views on SlideShare
944
Embed Views
0

Actions

Likes
0
Downloads
0
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as OpenOffice

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

2008 PGSAS G-nomes 2008 PGSAS G-nomes Presentation Transcript

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