Restriction fragment length polymorphisms can be used to detect linkage In

this hypothetical pedigree, the father and half of the children are affected (red circles and squares) with Huntington disease, an autosomal dominant disease. The father is heterozygous (Hh) and will pass the chromosome with the Huntington gene to approximately half of his offspring. The father is also heterozygous for RFLP alleles A and C; each child receives one of these two alleles from the father. The mother is homozygous for RFLP allele B, so all children receive the B allele from her. (a) In this case, there is no correspondence between the inheritance of the RFLP allele and inheritance of the disease — children with the disease are just as likely to carry the A allele as they are the C allele. Thus the disease gene and RFLP alleles segregate independently and are not closely linked. (b) In this case, there is a close correspondence between the inheritance of the RFLP alleles and the presence of the disease—every child who inherits the C allele from the father also has the disease. This correspondence indicates that the RFLP is closely linked to the Huntington gene.

disease allele (H) or a normal allele (h); any child inheriting the Huntington-disease allele develops the disease, because it is an autosomal dominant disorder. The child also inherits one of the two RFLP alleles from the father, either A or C, which produces the corresponding RFLP pattern. In Figure 18.27a, there is no correspondence between the inheritance of the RFLP pattern and the inheritance of the disease: children who have inherited Huntington disease (and therefore the H allele) from their father are equally likely to have inherited the A or C RFLP pattern. Because, in this case, the H allele and the RFLP alleles segregate randomly, we know that they are not closely linked.

4 Figure 18.27b, on the other hand, shows that every child who inherits the C pattern from the father also inherits Huntington disease (and therefore the H allele), because the locus for the RFLP is closely linked to the locus for the disease-causing gene. The chromosomal location of the RFLP provides a general indication of the disease-causing locus. An examination of the cosegregation of other RFLPs from the same region can precisely determine the location of the gene. Actual RFLP patterns and part of the Huntington-disease gene are shown in 4 Figure 18.28.

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