by Gidon Schwartz, Education & Outreach Executive
Shavuot has an unusual place amongst the Jewish festivals. There are no active mitzvot like the shofar, fasting or the seder of other festivals (albeit we do all love cheesecake!). Shavuot, however, holds a really important place in a concurrent annual cycle: the agrarian calendar.
Shavuot is the time of the wheat harvest. During Temple times, this was marked by an offering of two wheat loaves on the altar of the Beit Hamikdash (temple). The gluten in these wheat products can make this an awkward event for many – we all know someone who has Crohn’s disease, is coeliac or just has a gluten intolerance. So, what is it about these conditions that make them more common within some families?
We often like to think of genetics as a nice, neat pattern, with inheritance fitting in to perfectly arranged boxes (or Punnett squares); “if I have the faulty gene, it means I will develop the dominant disorder,” or, “if I have both mutated copies of a gene I will develop the disorder,” but in reality, most traits and disorders are far more complex.
This means it isn’t just one gene that leads to the condition but the interaction of multiple genes, which also interact with the environment around you that ultimately leads from the genotype (what your DNA looks like) and your phenotype (what your body actually looks like). A nice trait to consider this with is height – there are around 20 genes that dictate height, but they are also dependent on the environment. For example, we know that diet is very important in determining height, and those that are malnourished as children do not grow to their full potential height.
Intolerance to wheat (and most other allergies) is actually your own body detecting what you have eaten and mistaking it for a dangerous foreign substance, and then raising an immune response to kill off the danger, leading to inflation, itching, or bloating. The main genes associated with this lack of tolerance is a family of genes called human leukocyte antigen (HLA) genes, and they are all in the same section of the same chromosome (known as a haplotype). Unlike the genes we test for at Jnetics, there are 7 variants of the HLA-DQ genes and over 95% of coeliac people have one of 2 forms of this haplotype. That does not mean everyone with one of these genetic variants will be a coeliac, in fact these haplotypes are found in up to 40% of the general population but only 1% of the population are estimated to be coeliac. To add another layer of complexity to this, the currently identified genes only explain half of all coeliac cases.
A very timely discovery was published this week. Scientists from the Francis Crick Institute, along with others from UCL and Imperial identified a gene called ETS2 (located on the long arm of chromosome 21) as playing a vital role in your immune response and tolerance to gluten. This study showed 95% of individuals with Crohn’s disease have a certain variant of this gene. The study showed that people with this variant gene produce a massively exaggerated immune response, by the white blood cells releasing a group of chemicals called cytokines. Cytokines cause swelling – which when used correctly by the body helps fight off invading microbes. However, in this case, the response causes too much swelling – and the suffering of the symptoms related to Crohn’s disease and other inflammatory bowel diseases.
This is even more relevant to our community, as Ashkenazi Jews are 2 – 4 times more likely to have Crohn’s disease than the general population. Now such a key gene has been identified, targeted medical treatments can be developed, enabling there to be treatment for these conditions.
The environment plays a part in this gluten intolerance, and possibly Crohn’s disease via another influencing factor, epigenetics. This is a relatively new branch of genetics, in which we are still at the early stages of understanding. Epigenetics is a process of marking or tagging our genes, and they are chemicals that are attached to your DNA, adapting its structure, and allowing different genes to be read in different ways (think of it like the vowels and notes added to Hebrew to make you able to read the text). These epigenetic tags can be influenced by your environment such as diet or atmospheric conditions.
All these factors make up our complex bodies and lead to the fact that some of us can eat and digest bread comfortably, whilst others cannot. Much of the genetics of the body’s reaction to wheat is still not fully understood by science today (all of science was not given to mankind all at once, like the Torah was on Shavuot) and who knows, it could be you to discover the next piece in the puzzle of genetics and how they interact with the environment to make us who we are.
