Polymorphism discovery informatics

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Polymorphism discovery informatics
Gabor T. Marth
Department of Biology Boston College Chestnut
Hill, MA 02467
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Types of sequence variations

• Substitution-type single-nucleotide
  polymorphisms are the most abundant form of
  sequence variations

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Are all substitutions SNPs?
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What is SNP discovery?

• comparative analysis of multiple sequences from
  the same region of the genome (redundant sequence
  coverage)

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Steps of SNP discovery
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SNP discovery in diverse sequences

• many different types of sequences are available
  for polymorphism discovery

genome
EST
WGS
BAC
BAC-end
restriction fragments

• early methods of SNP discovery focused on
  specific sequence types

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General SNP mining PolyBayes
sequence clustering simplifies to database search
with genome reference
multiple alignment by anchoring fragments to
genome reference
paralog filtering by counting mismatches weighed
by quality values
SNP detection by differentiating true
polymorphism from sequencing error using quality
values
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SNP validation

• Pooled sequencing

• Direct re-sequencing

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Genome-scale SNP mining projects

• Overlaps of large-insert clone sequences

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SNP genotyping

• SNP discovery which nucleotides in the genome
  are polymorphic?

a g aacgtttatgtgattccagtaaa
tacggca c t

• SNP genotyping which alleles does an individual
  carry at a nucleotide locus that is known to be
  polymorphic?

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Genotyping by sequence
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Genome variation landscape

• nucleotide diversity on human chromosomes