FOXP2

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FOXP2

• A Genomic Clue to What Makes Humans Unique

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Outline

• Part I- Identifying a unique genetic disease
• Part II- Finding Homologous Genes
• Part III- Aligning and comparing homologous
  sequences

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Part I- Identifying a unique genetic disease
KE Pedigree
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How was the gene found?

• Using a technique called FISH (Fluorescent
  In-situ Hybridization), scientists at Oxford
  isolated the mutation to a particular locus on
  Chromosome 7
• The HGP had a BAC (Bacterial Artificial
  Chromosome) sequenced from this region named
  NH0563O05

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• The BAC clone sequence is known

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Gene Prediction

• Suspecting an unknown gene was affected in this
  region in these patients, the scientists used
  Gene Prediction programs on this BAC clone
  sequence

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• They then compared this predicted gene with known
  genes with other bioinformatics tools.
• You can use BLAST to do the same.

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• Your BLAST results should look like this.

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Congratulations!

• Weve found the gene responsible for the
  Speech-language Disorder-1 in the KE family.

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Part II- Finding Homologous Genes

• After this gene was found in humans, other
  scientists studying human evolution wanted to
  know if a similar gene existed in other primates.
• The used cDNA arrays to isolate and sequence the
  mRNA of the FOXP2 gene in a number of primates
  and mice (used as an out-group).

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Part III- Aligning and comparing homologous
sequences

• Then these scientists used multiple alignment
  programs (CLUSTAL W) to compare the amino acid
  sequences encoded by these primate mRNAs to the
  human protein.

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Counting mutations over time

• Other studies have determined that humans and the
  great apes have a most recent common ancestor 4-7
  million years ago.
• Rodents and primates trace their common ancestor
  back to about 80-110 million years ago.

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• Are the differences in humans due to random
  mutation alone?
• What trait do we know of in humans that may be
  related to why we see a unique version of the
  FOXP2 protein in the human line?