Gene Mapping

A significant contribution of recombinant DNA technology has been to provide numerous genetic markers that can be used in gene mapping. One group of markers used in gene mapping comprises restriction fragment length polymorphisms (RFLPs, pronounced rifflips). RFLPs are variations (polymorphisms) in the patterns of fragments produced when DNA molecules are cut with the same restriction enzyme. If DNA from two persons is cut with the same restriction enzyme and different patterns of fragments are produced (IFigure 18.26), these persons must possess differences in their DNA sequences. These differences are inherited and can be used in mapping, similar to the way in which allelic differences are used to map conventional genes.

Traditionally, gene mapping has relied on the use of genetic differences that produce easily observable pheno-typic differences. Unfortunately, because most traits are influenced by multiple genes and the environment, the number of traits with a simple genetic basis suitable for use in mapping is limited. RFLPs provide a large number of genetic markers that can be used in mapping.

To illustrate mapping with RFLPs, let's again consider Huntington disease. As mentioned earlier, this disease is caused by an autosomal dominant gene but, until recently, the chromosomal location of the gene was unknown. A team of scientists led by James Gusella (see introduction to Chapter 5) set out to determine the location of the Huntington gene, in the hope that, when the gene was found, its biochemical basis could be determined and possi ble treatments might be suggested. DNA was collected from members of the largest known family with Huntington disease, who live near Lake Maracaibo in Venezuela.

The basic strategy employed in the search for the Huntington-disease gene and a number of other human disease-causing genes is to look for coinheritance of the disease-causing gene and an RFLP with a known chromosomal location. If the disease gene and the RFLP have been inherited together, they must be physically linked.

This approach is summarized in I Figure 18.27, which illustrates the coinheritance of two traits: (1) the presence or absence of Huntington disease and (2) the type of restriction pattern produced (pattern A or C). In the family shown, the father is heterozygous for Huntington disease (Hh) and is also heterozygous for a restriction pattern (AC). From the father, each child inherits either a Huntington-


BB hh

CB AB CB AB CB AB CB AB Hh hh Hh hh Hh hh Hh hh
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