• 6 classes
• 2 for SNP and 4 for gene expression
• 2 per group and will present in each class.
• Subjects and groups will be chosen randomly.
• Todays class is introductory, we will discuss
• Forward genetics – understanding a genotype
by understanding the phenotype.
• Reverse Genetics -
How often SNPs occur?
• One in 300 bases – 10 M.
Not all single-nucleotide
changes are SNPs, though.
To be classified as a SNP,
two or more versions of a
sequence must each be
present in at least one
percent of the general
Each combination is a haplotype!!!!
Not necessarily all 8 haplotypes exist!!!!
dbSNP and Hapmap project
• dbSNP: 2.5 million variations
• Haplotypes are blocks – hapmap focuses on those
– Nigeria, Japan, China, USA
Two Channel and single Channel microarray
Two channel – two conditions
Spike-in control probes are there
Used for Normalization
-Agilent dual mode; Eppendorf with
Single channel: One condition at a time.
Abundance of a transcript will not be
known only relative abundance.
Affymetrix: Genechip; Illumina BeadChip
Microarray and Bioinformatics
• Experimental design.
• Statistical data analysis.
• Data storage and visualization.
• Experimental design:
– Biological replicates.
– Technical replicate.
– Difficult – cant be easily replicated.
– Minimum Information About a Microarray
Experiment" (MIAME); 2001, nature genetics
• Data Analysis:
– Image Analysis – gridding of the spots
– Data processing:
• Background correction
• Visualization (MA Plot)
– M is log transformation and A is mean average scale
change -> Y is 0
• Data Processing:
– Normalization (Remove non-biological variation)
• Simplest way: Assume all arrays have same median
• Subtract median from each array
• Quantile normalization:
– Order values in each array
– Take average across probes
– Substitute probe intensity with average
– Change the original order
MC3830805/ -> ABO allele – international
journal of evolutionary biology
3990764/ -> Semantic modelling associated
with SNPs from hapmap data – Genomics and
• Group 2:
• We will discuss this paper.