Is a trait caused by genetic factors?

Sometimes, it’s not so easy to determine whether a trait is caused by genetic factors.  Traits can be variably expressive or incompletely penetrant.  Traits may be controlled by multiple genes, as we saw with epistasis and quantitative trait loci.  A single trait can also be influenced by both genetic and non-genetic factors.  In previous modules, we’ve looked at expected patterns of inheritance and phenotypic ratios for parents and offspring, in some cases tracking alleles and traits through multiple generations of controlled crosses.  Refer back to the module on Sex for a description of how such crosses can be used to show sex-linkage for the white eye and other phenotypes in Drosophila.

Controlled crosses are powerful genetic tools in organisms that can be manipulated in the lab.  But in humans and other organisms where controlled crosses are inappropriate, medical researchers turn to other tools of genetics to understand the causes of diseases and other phenotypic variation.  In this module, we will look at concordance studies and pedigree analysis.  While this section will focus primarily on examples from human genetics, these tools can be used to study any trait or any species.

Example: Celiac Disease

Do you know someone who follows a gluten-free diet?  This has become pretty common in the last several decades, with food suppliers meeting the demand for gluten-free products like breads, pasta, snacks, and desserts.

Glutens are a class of proteins found in wheat and certain other grains like barley and rye.  These proteins give products like breads and cakes their elasticity: during the baking process, crosslinks between protein chains form a mesh-like network.  This gives structure to the dough or batter, and air bubbles trapped in the network of protein chains make cakes and breads rise.  Different types of flour have different amounts of gluten. Bread flour typically has a higher gluten content, giving a denser network of gluten fibers and a chewier texture to the final product.  Pastry flour typically has a lower gluten content, and baked goods made with pastry flour are usually more delicate and tender.

Gluten-free flours are made from plants like rice or tapioca, which do not have gluten.  If you’ve had baked goods made with gluten-free flour, you may have noticed that the texture tends to be more crumbly than would be expected from the same food made with wheat-based flour.  This is because, without the network of gluten proteins, there is less structure to the batter or dough.

For some people, consuming gluten triggers unpleasant symptoms like digestive issues (diarrhea or constipation), skin rashes, or bloating. Celiac disease is a specific type of gluten sensitivity caused by an immune response to the gluten proteins.  The symptoms of celiac disease have been known for centuries, the connection of symptoms to wheat consumption was not recognized until the 1950’s.  This was after several decades of treating symptoms with restrictive diets that coincidently excluded wheat, often by promoting single foods like bananas or rice^[1].

Understanding why some people but not others develop gluten sensitivity (and immune response) was difficult. Celiac disease does appear to run in families: someone with a relative with celiac disease is more likely to also develop the disease than someone with no close relatives with the disease.

But is this because of shared DNA or a shared environment?  Families share DNA – and genetic traits – but they also share foods, environment, culture, and behaviors.  Those non-genetic factors can also influence family clusters of disease or other traits.  For example, if a family were all exposed to the same contaminated water, they might all develop the same rare disease, even if it were not caused by genetics.  So how do we determine the cause?

Today, we recognize celiac disease as a multifactorial immune disease, caused by both genetic and non-genetic factors.  To earn this knowledge required decades of work from many medical researchers.  Genetic tools like pedigree analysis, twin studies, and genetic association studies were used together to find the causes.  This module describes pedigree analysis and twin studies.