genomics, computing, economics & society
DESCRIPTION
Genomics, Computing, Economics & Society. 10 AM Tue 11-Oct 2005 Fairchild 177 week 4 of 14. MIT-OCW Health Sciences & Technology 508/510 Harvard Biophysics 101 Economics , Public Policy , Business , Health Policy - PowerPoint PPT PresentationTRANSCRIPT
MIT-OCW Health Sciences & Technology 508/510
Harvard Biophysics 101
Economics, Public Policy, Business, Health Policy
For more info see: http://karma.med.harvard.edu/wiki/Biophysics_101
10 AM Tue 11-Oct 2005 Fairchild 177 week 4 of 14
Genomics, Computing, Economics & Society
Class outline
(1) Topic priorities for homework since last class(2) Quantitative exercises: psycho-statistics, combinatorials, random/compression, exponential/logistic, bits, association & multi-hypotheses
(3) Project level presentation & discussion
(4) Sub-project reports & discussion:
Personalized Medicine & Energy Metabolism
(5) Discuss communication/presentation tools
(6) Topic priorities for homework for next class
Common Disease – Common Variant Theory. How common?
ApoE allele 4 : Alzheimer’s dementia, & hypercholesterolemia20% in humans, >97% in chimps
HbS 17% & G6PD 40% in a Saudi sample
CCR532 : resistance to HIV 9% in caucasians
SNPs & Covariance in proteins
e4 20% ApoE e3 80%
Ancestral = Arg 112 Thr 61
One form of HIV-1 Resistance
Association test for CCR-5 & HIV resistanceAlleles Obs Neg ObsSeroPos total ExpecNeg ExpecPosCCR-5+ 1278 1368 2646 1305 1341 ccr-5 130 78 208 103 105total 1408 1446 2854
Pdof=(r-1)(c-1)=1 ChiSq=sum[(o-e) 2̂/e]= 15.6 0.00008
Samson et al. Nature 1996 382:722-5
But what if we test more than one locus?
The future of genetic studies of complex human diseases. Ref (Note above graphs are active spreadsheets -- just click)
Y= Number of Sib Pairs (Association)X= Population frequency (p)
GRR=1.5, #alleles=1E6
1E+2
1E+3
1E+4
1E+5
1E+6
1E+7
1E+8
1E+9
1E+10
1E-091E-081E-071E-060.000010.00010.0010.010.11
[based on Risch & Merikangas (1996) Science 273: 1516]
| Y= Number of Sib Pairs (Association)X= Genotypic Relative Risk (GRR)
#alleles=1E6, p=0.5 (population frequency)
1E+1
1E+2
1E+3
1E+4
1E+5
1E+6
1E+7
1E+8
0.001 0.01 0.1 1 10 100 1000 10000
1.001 1.01 1.1 2 11 101 1,001 10,001
1-GRRGRR
[based on Risch & Merikangas (1996) Science 273: 1516]|
|
Y= Number of Sib Pairs (Assocation)X= Number of Alleles (Hypotheses) Tested
GRR=1.5, p= 0.5 (population frequency)
0
200
400
600
800
1,000
1,200
1,400
1,600
1E+4 1E+6 1E+8 1E+10 1E+12 1E+14 1E+16 1E+18 1E+20 1E+22
[based on Risch & Merikangas (1996) Science 273: 1516]|
GRR = Genotypic relative risk
How many "new" mutations?
G= generations of exponential population growth = 5000N'= population size = 6 x 109 now; N= 104 pre-Gm= mutation rate per bp per generation = 10-8 to 10-9 (ref)L= diploid genome = 6 x 109 bp ekG = N'/N; so k= 0.0028 Av # new mutations < Lektm = 4 x 103 to 4 x 104
per genome t=1 to 5000
Take home: "High genomic deleterious mutation rates in hominids"accumulate over 5000 generations & confound linkage methodsAnd common (causative) allele assumptions.
Class outline
(1) Topic priorities for homework since last class
(2) Quantitative exercise
(3) Project level presentation & discussion
(4) Sub-project reports & discussion
(5) Discuss communication/presentation tools
(6) Topic priorities, homework for next class