SlideShare une entreprise Scribd logo

Association mapping using local genealogies

•
•
M
mailund
Santé & Médecine
1  sur  37
Télécharger pour lire hors ligne
Association Mapping Through local genealogies Thomas Mailund Bioinformatics Research Center http://www.birc.au.dk/
Gunshot wounds Car accidents Smoking induced lung cancer “Genetic” Diseases Cardiovascular disease Obesity Diabetes 2 Alzheimer Schizophrenia BRCA1 breast cancer Cystic fibrosis Haemophilia
Disease Mapping... Locate disease-affecting polymorphism Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Disease Mapping... Markers are locally correlated Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Disease Mapping... Search for indirect signals Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Indirect Association “Tag” markers Unobserved marker Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
Indirect Multi-Marker Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
The Ancestral Recombination Graph Hudson 1990, Griffith and Marjoram 1996
Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
Clustering on a Tree Disease affecting mutation
Clustering on a Tree Complete penetrance Incomplete penetrance Spurious disease
Clustering on a Tree 25% Case/control clustering is not random on the tree... 75% 40% 60%
Using “Perfect Phylogenies” Use the four-gamete test to find regions that can be explained by a tree with no recurrent mutations Mailund, Besenbacher & Schierup 2006
Using “Perfect Phylogenies” Build trees for each such region Mailund, Besenbacher & Schierup 2006
Using “Perfect Phylogenies” Each marker splits a sub-tree in two Mailund, Besenbacher & Schierup 2006
Using “Perfect Phylogenies” Each marker splits a sub-tree in two Mailund, Besenbacher & Schierup 2006
Using “Perfect Phylogenies” Each marker splits a sub-tree in two Mailund, Besenbacher & Schierup 2006
Scoring the Clustering Red=cases Green=controls Are the case chromosomes significantly over-represented in some clusters?
Wild-types Mutation Mutants We can place “mutations” on the tree edges and partition chromosomes into “mutants” and “wild-types” and test for different distributions of cases and controls
Wild-types Mutation Mutants Use average or maximum to score the tree Average is kosher Bayesian stats; maximum needs to be corrected for over-fitting.
Whole genome breast cancer
Localisation Accuracy A single causal mutation Max BF / min p-value used as point estimate
Localisation Accuracy Two causal mutations Max BF / min p-value used as point estimate
Power to detect association power 100 80 Percentage 60 40 20 QBlossoc Student's t−test 0 0.05 0.10 0.15 Susceptibility allelle frequency
Blossoc (BLOck aSSOCiation) Homepage: www.birc.au.dk/~mailund/Blossoc Command line and graphical user interface (with limited functionality)
Blossoc (BLOck aSSOCiation) Homepage: www.birc.au.dk/~mailund/Blossoc Fast enough to analyse tens of thousands of individuals in hundred of thousands of markers in a few days on a desktop computer...
Thank you! More information at http://www.birc.au.dk/~mailund/association-mapping/

Recommandé

Epidemiologisk FredagsmøDe 15 2 2008
Epidemiologisk FredagsmøDe 15 2 2008Epidemiologisk FredagsmøDe 15 2 2008
Epidemiologisk FredagsmøDe 15 2 2008mailund
 
Time table
Time tableTime table
Time tableDebarun Sengupta
 
Measures of Linkage Disequilibrium
Measures of Linkage DisequilibriumMeasures of Linkage Disequilibrium
Measures of Linkage DisequilibriumAwais Khan
 
Creating a Kinship Matrix Using MSA
Creating a Kinship Matrix Using MSACreating a Kinship Matrix Using MSA
Creating a Kinship Matrix Using MSAheathermerk
 
GEE & GLMM in GWAS
GEE & GLMM in GWASGEE & GLMM in GWAS
GEE & GLMM in GWASJinseob Kim
 
Accelerating GWAS epistatic interaction analysis methods
Accelerating GWAS epistatic interaction analysis methodsAccelerating GWAS epistatic interaction analysis methods
Accelerating GWAS epistatic interaction analysis methodsPriscill Orue Esquivel
 
Probability And Stats Intro
Probability And Stats IntroProbability And Stats Intro
Probability And Stats Intromailund
 
linkage
linkagelinkage
linkageDUSHYANT DUBE
 

Recommandé

Epidemiologisk FredagsmøDe 15 2 2008
Epidemiologisk FredagsmøDe 15 2 2008Epidemiologisk FredagsmøDe 15 2 2008
Epidemiologisk FredagsmøDe 15 2 2008mailund
 
Time table
Time tableTime table
Time tableDebarun Sengupta
 
Measures of Linkage Disequilibrium
Measures of Linkage DisequilibriumMeasures of Linkage Disequilibrium
Measures of Linkage DisequilibriumAwais Khan
 
Creating a Kinship Matrix Using MSA
Creating a Kinship Matrix Using MSACreating a Kinship Matrix Using MSA
Creating a Kinship Matrix Using MSAheathermerk
 
GEE & GLMM in GWAS
GEE & GLMM in GWASGEE & GLMM in GWAS
GEE & GLMM in GWASJinseob Kim
 
Accelerating GWAS epistatic interaction analysis methods
Accelerating GWAS epistatic interaction analysis methodsAccelerating GWAS epistatic interaction analysis methods
Accelerating GWAS epistatic interaction analysis methodsPriscill Orue Esquivel
 
Probability And Stats Intro
Probability And Stats IntroProbability And Stats Intro
Probability And Stats Intromailund
 
linkage
linkagelinkage
linkageDUSHYANT DUBE
 
SNPs Presentation Cavalcanti Lab
SNPs Presentation Cavalcanti LabSNPs Presentation Cavalcanti Lab
SNPs Presentation Cavalcanti Labjsrep91
 
Intro gwas
Intro gwasIntro gwas
Intro gwasOmar Yang
 
Ch5 linkage
Ch5 linkageCh5 linkage
Ch5 linkagePratheep Sandrasaigaran
 
Estimation of Linkage Disequilibrium using GGT2 Software
Estimation of Linkage Disequilibrium using GGT2 SoftwareEstimation of Linkage Disequilibrium using GGT2 Software
Estimation of Linkage Disequilibrium using GGT2 SoftwareAwais Khan
 
Lecture 3 l dand_haplotypes_full
Lecture 3 l dand_haplotypes_fullLecture 3 l dand_haplotypes_full
Lecture 3 l dand_haplotypes_fullLekki Frazier-Wood
 
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...Mapping and Applications of Linkage Disequilibrium and Association Mapping in...
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...FAO
 
Epi519 Gwas Talk
Epi519 Gwas TalkEpi519 Gwas Talk
Epi519 Gwas Talkjoshbis
 
Genelinkagemap
GenelinkagemapGenelinkagemap
Genelinkagemapsarahhg
 
Introduction to association mapping and tutorial using tassel
Introduction to association mapping and tutorial using tasselIntroduction to association mapping and tutorial using tassel
Introduction to association mapping and tutorial using tasselAwais Khan
 
GWAS
GWASGWAS
GWASCheryl Miner
 
Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...
Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...
Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...CGIAR Research Program on Roots, Tubers and Bananas
 
How to solve linkage map problems
How to solve linkage map problemsHow to solve linkage map problems
How to solve linkage map problemsmartyynyyte
 
Genome wide association studies seminar
Genome wide association studies seminarGenome wide association studies seminar
Genome wide association studies seminarVarsha Gayatonde
 
Genetic Linkage
Genetic LinkageGenetic Linkage
Genetic LinkageJolie Yu
 
GWAS in a model organism: Arabidopsis thaliana
GWAS in a model organism: Arabidopsis thalianaGWAS in a model organism: Arabidopsis thaliana
GWAS in a model organism: Arabidopsis thalianaGolden Helix Inc
 
Genome Mapping
Genome MappingGenome Mapping
Genome Mappingruchibioinfo
 
مذكرة انجليزى kg2
مذكرة انجليزى kg2مذكرة انجليزى kg2
مذكرة انجليزى kg2أمنية وجدى
 
Asdff
AsdffAsdff
Asdffguest5738fc5
 
Asdff
AsdffAsdff
Asdffguest5738fc5
 
Asdff
AsdffAsdff
Asdffguest5738fc5
 
Brighter tab by paramore
Brighter tab by paramoreBrighter tab by paramore
Brighter tab by paramoreCristian
 
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...Jessica Tams
 

Contenu connexe

En vedette

SNPs Presentation Cavalcanti Lab
SNPs Presentation Cavalcanti LabSNPs Presentation Cavalcanti Lab
SNPs Presentation Cavalcanti Labjsrep91
 
Estimation of Linkage Disequilibrium using GGT2 Software
Estimation of Linkage Disequilibrium using GGT2 SoftwareEstimation of Linkage Disequilibrium using GGT2 Software
Estimation of Linkage Disequilibrium using GGT2 SoftwareAwais Khan
 
Lecture 3 l dand_haplotypes_full
Lecture 3 l dand_haplotypes_fullLecture 3 l dand_haplotypes_full
Lecture 3 l dand_haplotypes_fullLekki Frazier-Wood
 
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...Mapping and Applications of Linkage Disequilibrium and Association Mapping in...
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...FAO
 
Epi519 Gwas Talk
Epi519 Gwas TalkEpi519 Gwas Talk
Epi519 Gwas Talkjoshbis
 
Genelinkagemap
GenelinkagemapGenelinkagemap
Genelinkagemapsarahhg
 
Introduction to association mapping and tutorial using tassel
Introduction to association mapping and tutorial using tasselIntroduction to association mapping and tutorial using tassel
Introduction to association mapping and tutorial using tasselAwais Khan
 
How to solve linkage map problems
How to solve linkage map problemsHow to solve linkage map problems
How to solve linkage map problemsmartyynyyte
 
Genome wide association studies seminar
Genome wide association studies seminarGenome wide association studies seminar
Genome wide association studies seminarVarsha Gayatonde
 
Genetic Linkage
Genetic LinkageGenetic Linkage
Genetic LinkageJolie Yu
 
GWAS in a model organism: Arabidopsis thaliana
GWAS in a model organism: Arabidopsis thalianaGWAS in a model organism: Arabidopsis thaliana
GWAS in a model organism: Arabidopsis thalianaGolden Helix Inc
 

En vedette (16)

SNPs Presentation Cavalcanti Lab
SNPs Presentation Cavalcanti LabSNPs Presentation Cavalcanti Lab
SNPs Presentation Cavalcanti Lab
 
Intro gwas
Intro gwasIntro gwas
Intro gwas
 
Ch5 linkage
Ch5 linkageCh5 linkage
Ch5 linkage
 
Estimation of Linkage Disequilibrium using GGT2 Software
Estimation of Linkage Disequilibrium using GGT2 SoftwareEstimation of Linkage Disequilibrium using GGT2 Software
Estimation of Linkage Disequilibrium using GGT2 Software
 
Lecture 3 l dand_haplotypes_full
Lecture 3 l dand_haplotypes_fullLecture 3 l dand_haplotypes_full
Lecture 3 l dand_haplotypes_full
 
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...Mapping and Applications of Linkage Disequilibrium and Association Mapping in...
Mapping and Applications of Linkage Disequilibrium and Association Mapping in...
 
Epi519 Gwas Talk
Epi519 Gwas TalkEpi519 Gwas Talk
Epi519 Gwas Talk
 
Genelinkagemap
GenelinkagemapGenelinkagemap
Genelinkagemap
 
Introduction to association mapping and tutorial using tassel
Introduction to association mapping and tutorial using tasselIntroduction to association mapping and tutorial using tassel
Introduction to association mapping and tutorial using tassel
 
GWAS
GWASGWAS
GWAS
 
Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...
Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...
Application of Genome-Wide Association Study (GWAS) and transcriptomics to st...
 
How to solve linkage map problems
How to solve linkage map problemsHow to solve linkage map problems
How to solve linkage map problems
 
Genome wide association studies seminar
Genome wide association studies seminarGenome wide association studies seminar
Genome wide association studies seminar
 
Genetic Linkage
Genetic LinkageGenetic Linkage
Genetic Linkage
 
GWAS in a model organism: Arabidopsis thaliana
GWAS in a model organism: Arabidopsis thalianaGWAS in a model organism: Arabidopsis thaliana
GWAS in a model organism: Arabidopsis thaliana
 
Genome Mapping
Genome MappingGenome Mapping
Genome Mapping
 

Similaire à Association mapping using local genealogies

Brighter tab by paramore
Brighter tab by paramoreBrighter tab by paramore
Brighter tab by paramoreCristian
 
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...Jessica Tams
 
Precision Bearing House, Industrial Automation | PBH
Precision Bearing House, Industrial Automation | PBHPrecision Bearing House, Industrial Automation | PBH
Precision Bearing House, Industrial Automation | PBHPrecision Bearing House
 

Similaire à Association mapping using local genealogies (8)

مذكرة انجليزى kg2
مذكرة انجليزى kg2مذكرة انجليزى kg2
مذكرة انجليزى kg2
 
Asdff
AsdffAsdff
Asdff
 
Asdff
AsdffAsdff
Asdff
 
Asdff
AsdffAsdff
Asdff
 
Brighter tab by paramore
Brighter tab by paramoreBrighter tab by paramore
Brighter tab by paramore
 
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...
What Do Publishers Look For and What Should a Developer Look For | Pattera Ap...
 
Precision Bearing House, Industrial Automation | PBH
Precision Bearing House, Industrial Automation | PBHPrecision Bearing House, Industrial Automation | PBH
Precision Bearing House, Industrial Automation | PBH
 
At the clothes_shop
At the clothes_shopAt the clothes_shop
At the clothes_shop
 

Plus de mailund

Chapter 9 divide and conquer handouts with notes
Chapter 9 divide and conquer handouts with notesChapter 9 divide and conquer handouts with notes
Chapter 9 divide and conquer handouts with notesmailund
 
Chapter 9 divide and conquer handouts
Chapter 9 divide and conquer handoutsChapter 9 divide and conquer handouts
Chapter 9 divide and conquer handoutsmailund
 
Chapter 9 divide and conquer
Chapter 9 divide and conquerChapter 9 divide and conquer
Chapter 9 divide and conquermailund
 
Chapter 7 recursion handouts with notes
Chapter 7 recursion handouts with notesChapter 7 recursion handouts with notes
Chapter 7 recursion handouts with notesmailund
 
Chapter 7 recursion handouts
Chapter 7 recursion handoutsChapter 7 recursion handouts
Chapter 7 recursion handoutsmailund
 
Chapter 7 recursion
Chapter 7 recursionChapter 7 recursion
Chapter 7 recursionmailund
 
Chapter 5 searching and sorting handouts with notes
Chapter 5 searching and sorting handouts with notesChapter 5 searching and sorting handouts with notes
Chapter 5 searching and sorting handouts with notesmailund
 
Chapter 5 searching and sorting handouts
Chapter 5 searching and sorting handoutsChapter 5 searching and sorting handouts
Chapter 5 searching and sorting handoutsmailund
 
Chapter 5 searching and sorting
Chapter 5 searching and sortingChapter 5 searching and sorting
Chapter 5 searching and sortingmailund
 
Chapter 4 algorithmic efficiency handouts (with notes)
Chapter 4 algorithmic efficiency handouts (with notes)Chapter 4 algorithmic efficiency handouts (with notes)
Chapter 4 algorithmic efficiency handouts (with notes)mailund
 
Chapter 4 algorithmic efficiency handouts
Chapter 4 algorithmic efficiency handoutsChapter 4 algorithmic efficiency handouts
Chapter 4 algorithmic efficiency handoutsmailund
 
Chapter 4 algorithmic efficiency
Chapter 4 algorithmic efficiencyChapter 4 algorithmic efficiency
Chapter 4 algorithmic efficiencymailund
 
Chapter 3 introduction to algorithms slides
Chapter 3 introduction to algorithms slidesChapter 3 introduction to algorithms slides
Chapter 3 introduction to algorithms slidesmailund
 
Chapter 3 introduction to algorithms handouts (with notes)
Chapter 3 introduction to algorithms handouts (with notes)Chapter 3 introduction to algorithms handouts (with notes)
Chapter 3 introduction to algorithms handouts (with notes)mailund
 
Chapter 3 introduction to algorithms handouts
Chapter 3 introduction to algorithms handoutsChapter 3 introduction to algorithms handouts
Chapter 3 introduction to algorithms handoutsmailund
 
Ku 05 08 2009
Ku 05 08 2009Ku 05 08 2009
Ku 05 08 2009mailund
 
Neural Networks
Neural NetworksNeural Networks
Neural Networksmailund
 
Probability And Stats Intro2
Probability And Stats Intro2Probability And Stats Intro2
Probability And Stats Intro2mailund
 
Linear Regression Ex
Linear Regression ExLinear Regression Ex
Linear Regression Exmailund
 
Course Introduction
Course IntroductionCourse Introduction
Course Introductionmailund
 

Plus de mailund (20)

Chapter 9 divide and conquer handouts with notes
Chapter 9 divide and conquer handouts with notesChapter 9 divide and conquer handouts with notes
Chapter 9 divide and conquer handouts with notes
 
Chapter 9 divide and conquer handouts
Chapter 9 divide and conquer handoutsChapter 9 divide and conquer handouts
Chapter 9 divide and conquer handouts
 
Chapter 9 divide and conquer
Chapter 9 divide and conquerChapter 9 divide and conquer
Chapter 9 divide and conquer
 
Chapter 7 recursion handouts with notes
Chapter 7 recursion handouts with notesChapter 7 recursion handouts with notes
Chapter 7 recursion handouts with notes
 
Chapter 7 recursion handouts
Chapter 7 recursion handoutsChapter 7 recursion handouts
Chapter 7 recursion handouts
 
Chapter 7 recursion
Chapter 7 recursionChapter 7 recursion
Chapter 7 recursion
 
Chapter 5 searching and sorting handouts with notes
Chapter 5 searching and sorting handouts with notesChapter 5 searching and sorting handouts with notes
Chapter 5 searching and sorting handouts with notes
 
Chapter 5 searching and sorting handouts
Chapter 5 searching and sorting handoutsChapter 5 searching and sorting handouts
Chapter 5 searching and sorting handouts
 
Chapter 5 searching and sorting
Chapter 5 searching and sortingChapter 5 searching and sorting
Chapter 5 searching and sorting
 
Chapter 4 algorithmic efficiency handouts (with notes)
Chapter 4 algorithmic efficiency handouts (with notes)Chapter 4 algorithmic efficiency handouts (with notes)
Chapter 4 algorithmic efficiency handouts (with notes)
 
Chapter 4 algorithmic efficiency handouts
Chapter 4 algorithmic efficiency handoutsChapter 4 algorithmic efficiency handouts
Chapter 4 algorithmic efficiency handouts
 
Chapter 4 algorithmic efficiency
Chapter 4 algorithmic efficiencyChapter 4 algorithmic efficiency
Chapter 4 algorithmic efficiency
 
Chapter 3 introduction to algorithms slides
Chapter 3 introduction to algorithms slidesChapter 3 introduction to algorithms slides
Chapter 3 introduction to algorithms slides
 
Chapter 3 introduction to algorithms handouts (with notes)
Chapter 3 introduction to algorithms handouts (with notes)Chapter 3 introduction to algorithms handouts (with notes)
Chapter 3 introduction to algorithms handouts (with notes)
 
Chapter 3 introduction to algorithms handouts
Chapter 3 introduction to algorithms handoutsChapter 3 introduction to algorithms handouts
Chapter 3 introduction to algorithms handouts
 
Ku 05 08 2009
Ku 05 08 2009Ku 05 08 2009
Ku 05 08 2009
 
Neural Networks
Neural NetworksNeural Networks
Neural Networks
 
Probability And Stats Intro2
Probability And Stats Intro2Probability And Stats Intro2
Probability And Stats Intro2
 
Linear Regression Ex
Linear Regression ExLinear Regression Ex
Linear Regression Ex
 
Course Introduction
Course IntroductionCourse Introduction
Course Introduction
 

Dernier

Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdfLippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdfSreeja Cherukuru
 
Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.Prerana Jadhav
 
Basic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdfBasic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdfDivya Kanojiya
 
call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...
call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...
call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...saminamagar
 
History and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdfHistory and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdfSasikiranMarri
 
Glomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptxGlomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptxDr.Nusrat Tariq
 
LUNG TUMORS AND ITS CLASSIFICATIONS.pdf
LUNG TUMORS AND ITS CLASSIFICATIONS.pdfLUNG TUMORS AND ITS CLASSIFICATIONS.pdf
LUNG TUMORS AND ITS CLASSIFICATIONS.pdfDolisha Warbi
 
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisVarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisGolden Helix
 
PULMONARY EDEMA AND ITS MANAGEMENT.pdf
PULMONARY EDEMA AND ITS MANAGEMENT.pdfPULMONARY EDEMA AND ITS MANAGEMENT.pdf
PULMONARY EDEMA AND ITS MANAGEMENT.pdfDolisha Warbi
 
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️saminamagar
 
Culture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptxCulture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptxDr. Dheeraj Kumar
 
POST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptxPOST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptxvirengeeta
 
Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!ibtesaam huma
 
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATROApril 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATROKanhu Charan
 
Apiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.pptApiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.pptkedirjemalharun
 
Pharmaceutical Marketting: Unit-5, Pricing
Pharmaceutical Marketting: Unit-5, PricingPharmaceutical Marketting: Unit-5, Pricing
Pharmaceutical Marketting: Unit-5, PricingArunagarwal328757
 
Radiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxRadiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxDr. Dheeraj Kumar
 
See the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy PlatformSee the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy PlatformKweku Zurek
 
The next social challenge to public health: the information environment.pptx
The next social challenge to public health: the information environment.pptxThe next social challenge to public health: the information environment.pptx
The next social challenge to public health: the information environment.pptxTina Purnat
 
Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Mohamed Rizk Khodair
 

Dernier (20)

Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdfLippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
 
Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.
 
Basic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdfBasic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdf
 
call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...
call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...
call girls in Connaught Place DELHI 🔝 >༒9540349809 🔝 genuine Escort Service ...
 
History and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdfHistory and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdf
 
Glomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptxGlomerular Filtration rate and its determinants.pptx
Glomerular Filtration rate and its determinants.pptx
 
LUNG TUMORS AND ITS CLASSIFICATIONS.pdf
LUNG TUMORS AND ITS CLASSIFICATIONS.pdfLUNG TUMORS AND ITS CLASSIFICATIONS.pdf
LUNG TUMORS AND ITS CLASSIFICATIONS.pdf
 
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisVarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
 
PULMONARY EDEMA AND ITS MANAGEMENT.pdf
PULMONARY EDEMA AND ITS MANAGEMENT.pdfPULMONARY EDEMA AND ITS MANAGEMENT.pdf
PULMONARY EDEMA AND ITS MANAGEMENT.pdf
 
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in munirka DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
 
Culture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptxCulture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptx
 
POST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptxPOST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptx
 
Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!
 
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATROApril 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
 
Apiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.pptApiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.ppt
 
Pharmaceutical Marketting: Unit-5, Pricing
Pharmaceutical Marketting: Unit-5, PricingPharmaceutical Marketting: Unit-5, Pricing
Pharmaceutical Marketting: Unit-5, Pricing
 
Radiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxRadiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptx
 
See the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy PlatformSee the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy Platform
 
The next social challenge to public health: the information environment.pptx
The next social challenge to public health: the information environment.pptxThe next social challenge to public health: the information environment.pptx
The next social challenge to public health: the information environment.pptx
 
Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)
 

Association mapping using local genealogies

  • 1. Association Mapping Through local genealogies Thomas Mailund Bioinformatics Research Center http://www.birc.au.dk/
  • 2. Gunshot wounds Car accidents Smoking induced lung cancer “Genetic” Diseases Cardiovascular disease Obesity Diabetes 2 Alzheimer Schizophrenia BRCA1 breast cancer Cystic fibrosis Haemophilia
  • 3. Disease Mapping... Locate disease-affecting polymorphism Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 4. Disease Mapping... Markers are locally correlated Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 5. Disease Mapping... Search for indirect signals Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 6. Indirect Association “Tag” markers Unobserved marker Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 7. Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 8. Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 9. Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 10. Indirect Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 11. Indirect Multi-Marker Association Cases (affected) --A--------C--------A----G---X----T---C---A---- --T--------G--------A----G---X----C---C---A---- --A--------G--------G----G---X----C---C---A---- --A--------C--------A----G---X----T---C---A---- --T--------C--------A----G---X----T---C---A---- --T--------C--------A----T---X----T---A---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------A----G---X----T---C---G---- --T--------C--------A----T---X----T---C---A---- --A--------C--------A----G---X----T---C---A---- --A--------C--------G----T---X----C---A---A---- --A--------C--------A----G---X----C---C---G---- Controls (unaffected)
  • 12. The Ancestral Recombination Graph Hudson 1990, Griffith and Marjoram 1996
  • 13. Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
  • 14. Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
  • 15. Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
  • 16. Local Phylogenies For each “point” on the chromosome, the ARG determines a (local) tree:
  • 17. Clustering on a Tree Disease affecting mutation
  • 18. Clustering on a Tree Complete penetrance Incomplete penetrance Spurious disease
  • 19. Clustering on a Tree 25% Case/control clustering is not random on the tree... 75% 40% 60%
  • 20. Using “Perfect Phylogenies” Use the four-gamete test to find regions that can be explained by a tree with no recurrent mutations Mailund, Besenbacher & Schierup 2006
  • 21. Using “Perfect Phylogenies” Build trees for each such region Mailund, Besenbacher & Schierup 2006
  • 22. Using “Perfect Phylogenies” Each marker splits a sub-tree in two Mailund, Besenbacher & Schierup 2006
  • 23. Using “Perfect Phylogenies” Each marker splits a sub-tree in two Mailund, Besenbacher & Schierup 2006
  • 24. Using “Perfect Phylogenies” Each marker splits a sub-tree in two Mailund, Besenbacher & Schierup 2006
  • 25. Scoring the Clustering Red=cases Green=controls Are the case chromosomes significantly over-represented in some clusters?
  • 26.
  • 27. Wild-types Mutation Mutants We can place “mutations” on the tree edges and partition chromosomes into “mutants” and “wild-types” and test for different distributions of cases and controls
  • 28. Wild-types Mutation Mutants Use average or maximum to score the tree Average is kosher Bayesian stats; maximum needs to be corrected for over-fitting.
  • 29.
  • 30.
  • 32. Localisation Accuracy A single causal mutation Max BF / min p-value used as point estimate
  • 33. Localisation Accuracy Two causal mutations Max BF / min p-value used as point estimate
  • 34. Power to detect association power 100 80 Percentage 60 40 20 QBlossoc Student's t−test 0 0.05 0.10 0.15 Susceptibility allelle frequency
  • 35. Blossoc (BLOck aSSOCiation) Homepage: www.birc.au.dk/~mailund/Blossoc Command line and graphical user interface (with limited functionality)
  • 36. Blossoc (BLOck aSSOCiation) Homepage: www.birc.au.dk/~mailund/Blossoc Fast enough to analyse tens of thousands of individuals in hundred of thousands of markers in a few days on a desktop computer...
  • 37. Thank you! More information at http://www.birc.au.dk/~mailund/association-mapping/