Collins, Andrew Richard (1993) The construction and integration of genetic maps. University of Southampton, Doctoral Thesis.
Abstract
Genetic linkage maps describe the arrangement of genes and DNA markers according to their pattern of inheritance. Genes that are inherited together (linked) are situated close together on a linkage map and genes inherited independently are far apart. Of the two broad strategies for constructing such maps, multipoint mapping is concerned with the simultaneous analysis of several linked loci whereas the classical multiple pairwise methods are concerned with two-point comparisons between a trait locus and a number of marker loci. The MAP program implements the latter strategy and is shown to recover more realistic map distances, account for genetic interference and is better at recovering the correct order, in the presence of typing error.
A comprehensive genetic map may be used to provide connectivity for physical maps that typically span less than 10 Mb of DNA. Functions to transform genetic locations may be derived by stepwise regression using physical locations fromm cytogenetic and regional maps as the independent variable. There is an urgent need for the adoption of a location database that implements algorithms to combine these `projected' physical maps with physical data from pulsed-field gel electrophoresis and other techniques. A prototype system called Idb (location database) can perform this function and combine maps of other data types while maintaining a set of fully-referenced partial maps. The database generates a composite location in megabases that represents a synthesis of available information on locus order and distance. Tools essential for summary map construction are also described. These methods have been applied to a number of human chromosomes and are illustrated here applied to chromosome 9. The prospects for linkage mapping and map integration are discussed.
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