CASE 3 YOU, FROM A TO T: YOUR PERSONAL GENOME

The example of Claudia Gilmore illustrates how, through tests of her personal genome with regard to the BRCA1 and BRCA2 mutations, she became aware of her elevated risk of breast cancer. Your personal genome not only can tell you about your genetic risk factors for disease, but it also contains important information about your genetic ancestry. For example, your male ancestors can be traced through your Y chromosome. The regions at the tips in which the X and Y chromosomes share homology is only about 6% of the entire length of the Y chromosome. This means that 94% of the Y chromosome consists of sequences that are completely linked with one another because that portion of the chromosome does not pair with another chromosome and does not undergo crossing over.

Because of this complete linkage, each hereditary lineage of Y chromosomes is separate from every other lineage. As mutations occur along the Y chromosome, they are completely linked to any past mutations that may be present and also completely linked to any future mutations that may take place. The mutations therefore accumulate, and this allows the evolutionary history of a set of sequences to be reconstructed.

Fig. 17.14 shows an evolutionary tree based on the accumulation of mutations at a set of nucleotide sites along the Y chromosome. Each unique combination of nucleotides constitutes a Y-chromosome haplotype, or haploid genotype. In the figure, the most ancient Y chromosomes are at the top, and the accumulation of new mutations as the generations proceed results in the successive creation of new haplotypes. Each Y-chromosome lineage may leave some nonmutant descendants as well as some mutant descendants, and hence any or all of the sequences shown may coexist in a present-day population.

In human history, the mutations creating new Y-chromosome haplotypes were occurring at the same time as populations were migrating and founding new settlements across the globe, and so each geographically distinct population came to have a somewhat different set of Y-chromosome haplotypes. The differences among populations are offset to some extent by migration among populations, which mixes the geographical locations of various haplotypes. Nevertheless, the fact that the mutations accumulate through time and are completely linked allows the evolutionary history of the haplotypes to be reconstructed. It also enables Y chromosomes to be traced to their likely ethnic origin.

The worldwide distribution of real Y-chromosome lineages among human populations is shown in Fig. 17.15. The different colors in the pie charts represent different haplotypes. Neighboring populations tend to have more closely related Y chromosomes than more distant populations. Four major clusters of Y-chromosome lineages can be recognized in Fig. 17.15. One is concentrated in Africa, another in Southeast Asia and Australia, a third in Europe and central and western Asia, and the fourth in North and South America. These clusters correspond roughly with the spread of human settlements around the globe inferred from archaeological evidence.

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The implication of Fig. 17.15 is that the haplotype of your Y chromosome (if you have a Y chromosome) contains genetic information about its origin. And you can learn what this information is from genetic testing companies that sell direct-to-consumer (DTC) services. Their tests are not regarded as medical devices and so are unregulated, and quality control is sometimes uncertain. Nevertheless, you can send saliva or other biological samples to a DTC provider, which will (for a fee) test your Y chromosome and send you a report that details its possible origin. Of course, because of recombination and independent assortment of genes in other chromosomes, the ethnic origin of your Y chromosome may have little or nothing to do with the ethnic origins of genes in any of your other chromosomes.