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DNA Sequencing
Sean Downes
DNA – Sequencing History
Walter Fiers at the University of Ghent (Ghent,
Belgium), between 1972 and 1976.
1973,Walter Gilbert and Allan Maxam at Harvard
reported the sequence of 24 basepairs.
The chain-termination method developed by
Frederick Sanger at the University of Cambridge, in
England in 1975.
In 1976–1977, Allan Maxam and Walter Gilbert
developed a DNA sequencing method based on
chemical modification of DNA and subsequent
cleavage at specific bases.
DNA - What is it?
(n) deoxyribonucleic acid, desoxyribonucleic
acid, DNA (biochemistry) a long linear polymer
found in the nucleus of a cell and formed from
nucleotides and shaped like a double helix;
associated with the transmission of genetic
information
DNA – What is it?
A DNA chain is basically like a twisted stepladder
made from 2 half-ladders, where each step is made
of a pair of complimentary halves.
The “half-steps” are called bases and they are
adenine, guanine, thymine, and cytosine, which are
abbreviated as A, G, T, and C. Chemically, A and G
are purines, and C and T are pyrimidines. For a good
fit, a pyrimidine must pair with a purine; in DNA, A
bonds with T, and G bonds with C. These are what
are referred to as DNA base pairs.
DNA – What does it do?
Chains of DNA bases form the 20 different amino
acids which make up all proteins.
DNA – 4 = 20 how...?
Since there are only 4 bases there must be
combinations of 3 of these, called codons, to make
20 amino acids. Why 3? Because 42 only makes 16
whereas 43 makes 64 (>20). It turns out that more
than one codon may make the same amino acid
making the code degenerate, but not ambiguous.
DNA - Sequencing
Since DNA forms the amino acids which produce the
proteins that (chained together) make up cell
structure, finding out how the proteins group to form
cells can potentially tell us how it happened,
happens, and will happen. This provides us the
opportunity to explore the origins of life, find the
causes for certain defects and diseases, and hopefully
the possibility of finding treatments or even cures.
DNA – Mapping Sequences
A complete strand of DNA in a chromosome may
contain hundreds of millions of base pairs ( the
human genome contains approximately 30,000 genes
consisting of roughly 3 billion base pairs) so it is
broken up, using various methods, into smaller
chains terminated by known “start” and “stop”
codons. These chains, or strings, are then analyzed
for their protein sequences (→ amino acid sequences
→ codon sequences).
DNA – Mapping Sequences
By looking at protein chains that make up defective
cells and comparing them to healthy cells,
“defective” genes causes by mutated or missing
sequences in the DNA that contribute to certain
diseases are being found.
So far genetic markers for only a small number of
rare conditions have been found.
DNA – and Finite State Automata
Hidden Markov Models are used to describe
protein sequence families.
DNA – Where to from here?
Considering the sheer volume of data generated
during DNA sequencing and combinations of
Sources
http://wordnetweb.princeton.edu/perl/webwn?s=dna
http://www.answers.com/topic/genetic-code
Automata, Computability, and ComplexityTheory and Applications – Elaine
Rich
http://seqcore.brcf.med.umich.edu/doc/educ/dnapr/sequencing.html
http://www.ornl.gov/sci/techresources/Human_Genome/faq/seqfacts.shtm
http://compbio.soe.ucsc.edu/ismb99.handouts/KK185FP.html#hmm