Gene Mapping in Humans

Efforts in mapping the human genome are hampered by the inability to perform desired crosses and the small number of progeny in most human families. Geneticists are restricted to analyses of pedigrees, which are often incomplete and provide limited information. Nevertheless, techniques have been developed that use pedigree data to analyze linkage, and a large number of human traits have been successfully mapped with the use of these methods. Because the number of progeny from any one mating is usually small, data from several families and pedigrees are usually combined to test for independent assortment. The methods used in these types of analysis are beyond the scope of this book, but an example will illustrate how linkage can be detected from pedigree data.

One of the first documented demonstrations of linkage in humans was between the locus for nail - patella syndrome and the locus that determines the ABO blood types. Nail - patella syndrome is an autosomal dominant disorder characterized by abnormal fingernails and absent or rudimentary kneecaps. The ABO blood types are determined by an autosomal locus with multiple alleles (Chapter 5). Linkage between the genes encoding these traits was established in families in which both traits segregate. Part of one such family is illustrated in i FIGURE 7.16.

Nail - patella syndrome is relatively rare; so we can assume that people having this trait are heterozygous (Nn); unaffected people are homozygous (nn). The ABO genotypes can be inferred from the phenotypes and the types of offspring produced. Person I-2 in Figure 7.16, for example, has blood type B, which has two possible genotypes: PP or Pi (see Figure 5.6). Because some of her offspring are blood type O (genotype ii) and must therefore have inherited an i allele from each parent, female I-2 must have genotype Pi. Similarly, the presence of blood type O offspring in generation II indicates that male I-1, with blood type A, also must carry an i allele and therefore has genotype Pi. The ABO and nail - patella genotypes for all persons in the pedigree are given below the squares and circles.

From generation II, we can see that the genes for nail - patella syndrome and the blood types do not appear to assort independently. The parents of this family are:

If the genes coding for nail - patella syndrome and the ABO blood types assorted independently, we would expect that some children in generation II would have blood type A and nail - patella syndrome, inheriting both the P and N genes from their father. However, all children in generation II with nail - patella syndrome have either blood type B or blood type O; all those with blood type A have normal nails and kneecaps. This outcome indicates that the arrangements of the alleles on the chromosomes of the crossed parents are:

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