文档介绍：Population Genomics
Gil McVean, Department of Statistics, Oxford
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Questions about ic variation
How different are our genomes?
How is the variation distributed within and between genomes?
What does variation tell us about human evolution?
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How different are our genomes?
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Serological techniques for detecting variation
Human
Rabbit
A
A
B
AB
O
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Blood group systems in humans
28 known systems
39 genes, 643 alleles
System
Genes
Alleles
ABO
ABO
102
Colton
C4A, C4B
7+
Chido-rodgers
AQP1
7
Colton
DAF
10
Diego
SLC4A1
78
Dombrock
DO
9
Duffy
FY
9
Gerbich
GYPC
9
GIL
AQP3
2
H/h
FUT1, FUT2
27/22
I
GCNT2
7
Indian
CD44
2
Kell
KEL, XK
33/30
Kidd
SLC14A1
8
Knops
CR1
24+
Landsteiner-Wiener
ICAM4
3
Lewis
FUT3, FUT6
14/20
Lutheran
LU
16
MNS
GYPA,GYPB,GYPE
43
OK
BSG
2
P-related
A4GALT, B3GALT3
14/5
RAPH-MER2
CD151
3
Rh
RHCE, RHD, RHAG
129
Scianna
ERMAP
4
Xg
XG, CD99
-
YT
ACHE
4
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Protein electroporesis
Changes in mass/charge ratio resulting from amino acid substitutions in proteins can be detected
In humans, about 30% of all loci show polymorphism with a 6% chance of a pair of randomly drawn alleles at a locus being different
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Starch or agar gel
Direction of travel
Lewontin and Hubby (1966)
Harris(1966)
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The rise of DNA sequence analysis
RFLPs
Cann et al 1987
Sequencing of small regions
Vigilant et al 1991
Whole genome sequencing
Ingman et al 2000
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The human genomes…
The draft human genome sequence was published in 2001
This is a mosaic from several individuals
Since then, several more genomes have been sequenced, at least partially
Shotgun sequencing variation discovery
Other methods have been developed to look for gross chromosomal differences
Nimblegen array CGH
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The International HapMap Project
Launched in 2002 with the goal of characterising single nucleotide variation betw