A nonlinear method for estimating nucleotide polymorphism from restriction maps

Restriction mapping is used to estimate nucleotide sequence polymorphismwhen the regions to be studied are too long or too numerous to besequenced. Restriction mapping is less costly than DNA sequencing, but itdoes not allow direct measurement of underlying nucleotide polymorphism. Itis therefore useful to be able to estimate underlying nucleotidepolymorphism from observations of polymorphism in restriction maps, as thisoffers some of the resolution afforded by DNA sequencing at a reduced cost.Previous estimators of underlying nucleotide polymorphism have assumed thateach restriction-enzyme- binding site contains, at most, a singlepolymorphic nucleotide position (the low-polymorphism-frequencyassumption), and this assumption has placed an upper limit on the level ofpolymorphism that can be resolved by these estimators. The present studydocuments an estimator which allows relaxation of this assumption. The newestimator more accurately estimates underlying nucleotide polymorphism whenthe polymorphism level is high enough to falsify the low-polymorphism-frequency assumption. The new estimator therefore yields good results fordata sets that are too divergent for analysis by present methods.