Table of Contents
Bio 101: Genomics & Computational Biology
Intro 2: Last week's take home lessons
DNA 1: Today's story, logic & goals
Connecting Genotype & Phenotype
Types of phenotypic effects of mutations
Types of mutations
Mutations & Polymorphisms
Haplotypes
Linkage & Association
Pharmacogenomics Gene/Enzyme Drug Quantitative effect
DNA Diversity Databases
Causative SNPs can be in non-coding repeats
Modes of inheritance
Today's story, logic & goals
Where do allele frequencies come from?
Directional & Stabilizing Selection
Ratio of strains over environments, e , times, te , selection coefficients, se, R = Ro exp[-?sete]
Where do allele frequencies come from?
Random Genetic Drift
Role of Genetic Exchange
Common Disease – Common Variant Theory. How common?
Are rare variants responsible for susceptibility to complex diseases?
Today's story, logic & goals
One form of HIV-1 Resistance
An association test for CCR-5 & HIV resistance
But what if we test more than one locus?
How many "new" polymorphisms?
Finding & Creating mutants
Pharmacogenomics Example
Caution: phases of human genetics
Today's story, logic & goals
Examples of random & systematic errors?
Sequence assembly
Ewing, Hillier, Wendl, & Green 1998
Examples of random & systematic errors?
Examples of systematic errors
Whole-genome shotgun
Weber & Myers 1997
Gel size separation
Systematic errors
Fluorescent primers or ddNTPs
New Genotyping
Use of DNA Chips for SNP ID & Scoring
Use of Mass Spec for Analysis and Scoring
Mass Spectrometry for Analysis and Scoring
Searching for (nearly) exact matches
Exact Sequence Searching
DNA 1: Today's story, logic & goals
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Author: George Church
Home Page: http://www.courses.fas.harvard.edu/~bphys101/
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