Every single one of us has almost the same set of approximately 20,000 genes. Thus, the differences among us are not the result of having different genes, but rather different versions of those genes. Take eye color, for example. There is no single “blue eyes” gene versus having a “brown eyes” gene. Instead, we all have many genes that contribute to our eye color, and the different versions of these many genes are what dictate our traits, which in this case would be which eye color we have. Importantly, not just observable traits are influenced by genes, but unobservable traits, like our mental abilities are also influenced by genes.
So what is a gene? You have probably heard about DNA, the ladder-shaped molecule that provides the building blocks for all human cells. Well, DNA is organized into short segments, which we call genes. An easy way to think about how DNA and genes are related is to think of DNA as a cookbook and genes as the recipes within the cookbook (thanks for the metaphor, 23 and me!). Genes are inherited from our parents and provide instructions for our cells on how to function and what traits to express.
Genes also come in different versions, known as single nucleotide polymorphisms, or SNPs for short. If genes are a recipe, SNPs are different versions of the same recipe. In the same way every family has its own version of a chocolate chip cookie recipe, we have our own version of the genetic information within each gene, called SNPs. SNPs are transmitted across generations and are what change up the recipes written within our genes, creating differences among the organisms in which SNPs reside. Most people will have the same genes, they just have different varieties of the same gene. Thus, the SNPs within a gene are responsible for variation between people. Many scientists have begun conducting genetic studies in order to investigate the role played by certain gene variants on important public health outcomes. One recent example of this was a study conducted by Perdue and colleagues (2019) investigating the role of SETBP1 gene in reading and reading problems. They chose to focus on the SETBP1 gene due to recent genetic evidence linking SNPs within this gene to several complex language-related neurodevelopmental syndromes and disorders. Since years of research has shown that reading and language are closely linked through the brain’s “reading circuit,” which is a term used to refer to the many parts of the brain needed to make reading happen, the researchers hypothesized that the SETBP1 gene would also be important for reading. Thus, they used a sample of 135 five- to twelve-year-old children to test this hypothesis by collecting saliva samples and giving them a number of reading, language, and general cognitive assessments.
Once the saliva samples were collected and analyzed, the researchers then tested how the different SNPs within the SETBP1 gene were related to each of the cognitive assessments and to neuroimaging data. Specifically, they had functional brain scans from 73 children from their original sample, showing which parts of the brain were being used (“activated”) during a specific task. They compared these functional brain scans to the genetic data on which SNPs each child had and to each child’s performance on the reading-related assessments in order to figure out which part of the brain was related to which different SNP, compare the different levels of brain activation in these brain areas, and ultimately assess how all these things were related to children’s reading skills.
For the genetic analyses looking at different SNPs within the SETBP1 gene and how they relate to how well children perform in different reading-related skills, the researchers found that the rs7230525 variant on the SETBP1 gene was important for children's phonological working memory for non-alphabetic items. What is phonological working memory for non-alphabetic items, you ask? It measures how accurately and efficiently children can remember and mentally manipulate a series of colors and numbers they are presented with for the first time. This specific skill is related to how well children learn to read, so children with the SNP associated with lower performance on this task are likely also be at risk for reading problems compared to children with the SNP associated with higher performance on this task.
When relating the neuroimaging data to the genetic data, the researchers found that different SNPs of the rs7230525 gene were also related to differences in brain activation in the right inferior parietal lobule (IPL). The IPL plays many important roles in the brain. It is involved with integrating our senses and motor movements and guiding our awareness of the space around us. The brain scans showed that children who did not do well on the phonological working memory task showed more activity in the IPL during a task that required them to read made-up words in comparison to children who did do well, who showed less IPL activity. Therefore, it seems that the IPL may be working extra hard to help children who struggle to read to integrate sight (reading a letter or word on a page) and sound information (pronouncing the letter or word) in order to read, especially in the case of made-up words.
Overall, these analyses tell us that the rs7230525 variant on the SETBP1 gene is important for reading performance. These results also provide scientific evidence in support of the continued use of genetic analyses to identify SNPs that are related to having a risk of reading difficulties in the future. We can learn a lot from looking at which recipes are contributing to making children unique!
Citation: Perdue, M. V., Mascheretti, S., Kornilov, S. A., Jasińska, K. K., Ryherd, K., Mencl, W. E., ... & Landi, N. (2019). Common variation within the SETBP1 gene is associated with reading-related skills and patterns of functional neural activation. Neuropsychologia, 130, 44-51.