A simple trait is one that arises from a single gene. Mutations in single genes, however, do not usually result in changes of just one trait. Sometimes these traits are easily observable phenotypes and sometimes they are not. The easily observable simple traits can provide clues to population history, while those not so easily observable (such as mild variants) must be further studied in order to better understand the effects of mutations in both general and specific cases.
No two alleles produce exactly the same gene product. This means that, while one can expect to see several sets of similar phenotypes, one can also expect to see a wide range of these phenotypes with a wide range of effects. This is b ecause genes can experience many different types of mutations. A gene could experience a gain of function mutation, which would produce a dominant allele. Similarly, a loss of function mutation produces recessive or dominant-negative alleles. Some mutations may produce alleles that are activity-altering mutations, creating alleles in which the gene product is changed and the efficiency of the product altered without a total loss or gain of function. Also a gene, and hence a mutation, may be syndromic and affect several traits.
An example of a disease resulting from an activity-altering mutation in a syndromic gene is cystic fibrosis (CF). CF is a non-dominant mutation in which a chloride channel is inactive or partially inactive, leading to a number of traits including pancreatic insufficiency and airway obstruction. Some mutations produce more severe results than do others. A combination of two severe mutations leads to severe CF, while two mild mutations or one mild and one severe may lead to mild or severe CF, depending on the specifics.
Much the same is true with phenylketonuria (PKU), where the majority of patients are heterogeneous for mutations. With PKU, it is unknown whether an individual who is heterozygous with a wild type allele is affected or not. It is possible that such an individual is not affected significiantly enough to warrant medical attention, exhibiting only very mild signs of PKU (mental retardation and behavioral disorders). Further study is needed on this both to ensure better care for these individuals and also to further understanding of the genome in general and PKU specifically.
It is possible to use simple traits in another way. In a single gene, there are virtually an infinite number of possible alleles and onle a small chance that a specific allele will arise independently in two different populations. Because of this, it is generally possible to assay the population history of a people by looking at the specific mutations found in a gene and the frequenceis of the mutations.
The capability to extrapolate population history from genetic diversity was explained by Scriver in his paper, "Every gene has two histories," (Memoires de la Societe Royale du Canada). Scriver's research focused on the Quebec province of Canada. This area features a mixed heritage, with a primarily French population settling before 1759 and a primarily English population settling thereafter. Due to political and cultural institutions, long family histories have been kept in many cases, and from these an excellent population history can be extrapolated. Also helpful in Scriver's research was the Quebec Network of Genetic Medicine, a pioneering program that tests infants for over thirty treatable genetic illnesses (including PKU) and has done so for more than twenty-five year.s. Thanks to this network, every case of PKU in Quebec in the past twenty yhears has been recorded.
This information, combined with the individual-specific sequencing of the gene responsible for PKU can be used to develop gene frequenceis specific for different subsets of the Quebec population. These derived frequenceies can then be compared to those found in the different parts of Europe from which the subpopulations came.
This comparision was done by Scriver. In several populations, he was able to determine where in Europe, and in many cases where specifically in France, their ancestors emigrated from. He was also able in one case to determine the presence of a Celtic ancestor in a populations's history. The results obtained by Scriver matched the recorded cultural history of the populations (where comparisons were possible), and appear to be a definite sign that population history can be used in diagnosing and treating genetic illness.
Generally then, it is possible to use simple traits (those for which only one gene is the cause) as a useful method for determining population history. Further study is needed to provide more complete data, but more and more is being learned every day. Hopefully this discovery will continue into the next millenium, as it is vital to the treatment of genetic illness that both the mechanism and the population history of the illness be known.