On the Analysis of Optical Mapping Data - University of Wisconsin ...

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Chapter 4
Detecting Copy Number Polymorphism
4.1 Introduction
Optical mapping: A physical map describes the locations of certain markers on a genome.
Restriction maps are physical maps induced by restriction enzymes, naturally produced
by bacteria to defend themselves by cutting up, or restricting, foreign DNA. The marker
associated with a restriction enzyme is the specific pattern it recognizes and cleaves; typically
a palindromic DNA sequence 4 to 8 base pairs long. Optical mapping (Schwartz et al.,
1993; Dimalanta et al., 2004) is a single molecule approach for the construction of ordered
restriction maps of genomic DNA. Briefly, hundreds of thousands of DNA molecules, sheared
using a shotgun process, are stretched by passing them through a micro-channel and attached
to a positively charged glass support. A restriction enzyme is then applied, cleaving the DNA
at sites recognized by the enzyme. The DNA molecules remain attached to the surface, but
the elasticity of the DNA recoils the molecule ends at the cleaved sites. The surface is
photographed under a microscope after being stained with a fluorochrome. Cleavage sites
can be identified as tiny gaps in the fluorescent line of the molecule, giving a local snapshot of
the complete restriction map. Unlike other restriction mapping techniques, optical mapping
bypasses the problem of reconstructing the order of the restriction fragments. Figure 1.1
gives a diagrammatic overview of optical mapping.
Goals: The goals of optical mapping are varied, but much of its usefulness arises from
being a fast and low cost surrogate to sequencing. Optical mapping has been used to assist