How do we study human genetics when most traits arise from multiple genes? It’s certainly more complicated that drawing a simple Punnett square.
Never fear, for model organisms are here!
Flying Hamsters and Human Biology
The flying hamster research has been going so well that Adrian and Ben decide that they should start collaborating to see if they can translate the research to human applications. To better determine how their research would best mesh together, they decide to get together for lunch to learn more about each other’s research. Ben explains to Adrian that his lab studies the genetics of skin pigmentation and skin cancer. Adrian is amazed at how complicated human genetics is compared to flying hamster genetics.
For example, skin pigmentation is affected by a number of different factors.
There are different types of skin pigmentation proteins, such as pheomelanin and eumelanin. The ratio between these types of melanin affects skin pigmentation, and this ratio is affected by a number of different genes.In addition to this ratio, the total amount of melanin also affects pigmentation. Again, the allelic composition of multiple alleles affects the total amount of melanin that is produced. Finally, the number of pigment-containing organelles, called melanosomes, and the number of cells possessing melanosomes, also affect pigmentation. With all these factors to consider, there are at least thirty or forty genes involved in human skin pigmentation!A trait which is determined by more than one factor, either genetic or environmental, is called multifactorial.
A subset of multifactorial traits is polygenic traits. A polygenic trait is determined by two or more genes, but not any environmental factors. However, be aware that although it is slightly inaccurate, many people refer to multifactorial and polygenic traits interchangeably.Studying multifactorial traits is not only difficult because of the number of genes involved, but also because the contribution of these genes is often additive.
In most of our flying hamster studies, a single trait was determined by a single gene, essentially like an on/off switch. For example, if a hamster is homozygous recessive at the coat color gene, it is white, but if it is homozygous dominant or heterozygous at the coat color gene, it is brown. However, most traits we observe in humans, such as skin pigmentation, aren’t ‘either/or.
‘ Most multifactorial traits are quantitative and vary over a continuous range of measurements.In the case of a quantitative trait, the genotype at each locus makes a contribution toward the final phenotype. In simplistic terms, say one person’s genotype at two pigmentation genes are a/a and b/b.
A second person with an a/a and B/b genotype might have a darker complexion than the first person. If we extrapolate this concept to multiple genes and possibly even multiple alleles for each gene, you can see how the tiny additive effects of multiple alleles and genes explain why we see so many different skin pigmentations in the human population. Recall how complicated it was to keep track of genotypes and phenotypes in just a dihybrid cross. Just imagine how crazy predicting phenotypes would be with thirty or forty genes in play!Many genes which affect skin pigmentation also play a role in skin cancer susceptibility. But, many other factors can also affect susceptibility to cancer, such as the genetics of DNA repair, cell division checkpoints, and programmed cell death. The complication of studying multifactorial genetics explains why some rare forms of cancer and other human diseases are often better understood than the more common ones.
Diseases which are defined by the genotype of a single gene, or even a few genes in a single pathway, are simply much easier to study. This is also the reason why model organism research is an important part of many strategies to understand human traits and disease.
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