Biology%20and%20Bioinformatics

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Biology and Bioinformatics
BI820 Seminar in Quantitative and Computational
Problems in Genomics
Gabor T. Marth
Department of Biology, Boston College marth_at_bc.edu
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The animal cell
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DNA the carrier of the genetic code
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DNA organization chromosomes
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Translation of genetic information
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DNA sequencing informatics
DNA sequencing informatics
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DNA organization
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Genome annotation
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De novo gene prediction
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Similarity-based gene prediction
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Gene localization
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Genetic mapping
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Gene function
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Expression analysis
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Protein structure
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RNA structure
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Protein structure prediction
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RNA structure prediction
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DNA evolution
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Evolution of chromosome organization
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Evolution of gene structure
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Evolution of DNA sequence
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Comparative genomics
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Phylogenetics
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Mechanisms of molecular evolution
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Sequence variations

• Human Genome Project produced a reference genome
  sequence that is 99.9 common to each human being

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Why do we care about variations?
phenotypic differences
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How do we find polymorphisms?

• look at multiple sequences from the same genome
  region

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SNP discovery -- Methods
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SNP discovery Computer tools
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SNP discovery Mining Projects
30,000 clones
gtCloneX ACGTTGCAACGT GTCAATGCTGCA
gtCloneY ACGTTGCAACGT GTCAATGCTGCA
25,901 clones (7,122 finished, 18,779 draft with
basequality values)
21,020 clone overlaps (124,356 fragment overlaps)
ACCTAGGAGACTGAACTTACTG
ACCTAGGAGACCGAACTTACTG
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SNP databases and characteristics

• access to variation data
• SNP properties
• reliability of information

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Where do variations come from?

• sequence variations are the result of mutation
  events

TAAAAAT
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Mutation rate

• higher mutation rate (µ) gives rise to more SNPS

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Recombination
accgttatgtaga
accgttatgtaga
accgttatgtaga
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Demographic history
small (effective) population size N

• different world populations have varying
  long-term effective population sizes (e.g.
  African N is larger than European)

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Modeling
stationary
expansion
collapse
bottleneck
past
history
present
MD (simulation)
AFS (direct form)
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Ancestral inference
modest but uninterrupted expansion
bottleneck
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The signatures of selection

• selective mutations influence the genealogy
  itself in the case of neutral mutations the
  processes of mutation and genealogy are decoupled

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Association and haplotype structure
linkage disequilibrium
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Computer simulations the Coalescent
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Medical utility?
?
clinical phenotype
molecular markers
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Mapping disease-causing loci
genetic linkage
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Forensic applications