How much difference there is in the mean quantitative phenotype between the different marker genotypes depends both on the strength of the effect of the QTL and on the tightness of linkage between the QTL and the marker locus. Suppose, for example, that two selected lines differ by a total of 100 units in some quantitative character. The line with the high value is homozygous 1/1 at a particular QTL, whereas the line with the low value is homozygous –/–, and each 1allele at this QTL accounts for 5 units of the total difference between the lines. Further, suppose that the high line is M/M and the low line is m/m at a marker locus 10 crossover units away from the QTL. Then, as shown in Figures 20-16, there are 4 units of difference between the average gamete carrying an M allele and the average gamete carrying an m allele in the segregating F2.
We can therefore calculate that 8 units of the difference between an M/M homozygote and an m/m homozygote are attributable to that QTL. Thus, we have accounted for 8 per cent of the average difference between the originally selected lines. The QTL actually accounts for 10 per cent of the difference; the discrepancy comes from the recombination between the marker gene and the QTL. We could then repeat this process by using marker loci at other locations along the chromosome and on different chromosomes to account for yet further fractions of the quantitative difference between the originally selected lines. This technique has been used to locate chromosomal segments associated with such characters as fruit weight in tomatoes, bristle number in Drosophila, and vegetative characters in maize.
In the maize case, 82 vegetative characters were examined in a cross between lines that differed in 20 DNA markers. On average, each character was significantly associated with 14 different markers, but the proportion of the character difference between the two lines that was associated with any particular marker was usually very small. Figure 20-17 shows the proportion of the statistically significant marker–character associations (on the y-axis) that accounted for different proportions of character difference between the lines. As Figure 20-17 shows, most associations accounted for less than 1 per cent of the character difference. Unfortunately, in human genetics, although marker-gene segregation can be used to localize single-gene disorders, the small size of human pedigree groups makes the marker segregation technique inapplicable for quantitative trait loci because there are too few progenies from any particular marker cross to provide any accuracy.
For many organisms (for example, humans), it is not possible to make homozygous lines differing in some trait and then cross them to produce a segregating generation. For such organisms, one can use the differences among sibs carrying different marker alleles from heterozygous parents. This method has much less power to find QTLs especially when the number of sibs in any family is small, as it is in human families. As a consequence, the attempts to map QTLs for human traits have not been very successful, although the marker segregation technique has been a success in finding loci whose mutations are responsible for single-gene disorders or for quantitative characters whose variation is strongly influenced by variation at one locus. For example, people vary in their ability to taste the substance phenylthiocarbamide (PTC).
Some can detect quite low concentrations, whereas others can detect only high concentrations or are unable to taste PTC at all. Linkage analysis using single nucleotide polymorphisms located a region on human chromosome 7q that accounted for about 75 per cent of the variation in taste sensitivity. This chromosomal region was already known to contain several genes coding for bitter taste receptor proteins. When the DNA of these genes was sequenced, three amino acid polymorphisms in one of the genes were found to be strongly associated with the difference between the taster and the nontaster phenotypes.
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