"Gene mapping" refers to the mapping of genes to specific locations on chromosomes. It is a critical step in the understanding of genetic diseases. There are two types of gene mapping:
Genetic Mapping - using linkage analysis to determine the relative position between two genes on a chromosome.
Physical Mapping - using all available techniques or information to determine the absolute position of a gene on a chromosome.
The ultimate goal of gene mapping is to clone genes, especially disease genes. Once a gene is cloned, we can determine its DNA sequence and study its protein product. For example, cystic fibrosis (CF) is the most common lethal inherited disease in the United States. As many as 1 in 2500 Americans of Northern European descent carry a gene with CF. In 1985, the gene was mapped to chromosome 7q31-q32 by linkage analysis. Four years later, it was cloned by Francis Collins and his co-workers. We now know that the disease is caused by the defect of a chloride channel (web link) - the protein product of this disease gene.
Linkage analysis
The genetic mapping is based on the linkage between "loci" (locations of genes). If two loci are usually inherited together, they are said to be "linked". Two loci on different chromosomes are not linked, because they are usually separated by independent assortment.
A locus (singular of loci) may have different sequences, referred to as alleles. Consider two loci A and B, each having two alleles (one from mother, another from father). A1 and A2 are the two alleles of locus A ; B1 and B2 are the two alleles of locus B. Initially, A1 and B1 are located on the same chromosome. A2 and B2 are located on a different chromosome.
Figure 10-A-1. Illustration of recombination between two loci A and B. (a) Two pairs of sister chromatids align during meiosis. A1 and B1 are located on the same chromosome. A2 and B2 are located on a different chromosome. (b) DNA crossover leads to recombination if the chiasma is located between the two loci. (c) DNA crossover does not lead to recombination if the chiasma is not located between the two loci.
The DNA crossover may cause recombination of loci A and B. Namely, A1 and B2 (or A2 and B1) are located on the same chromosome. The recombination frequency depends on the distance between the two loci and the position of crossover (the chiasma). The closer they are, the less likely the recombination will occur, because recombination occurs only when the chiasma is located between the two loci.
To apply this basic principle to map a disease gene, we need to analyze the pedigree and estimate recombination frequency.
http://www.web-books.com/MoBio/Free/Ch10A.htm
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