Lesson 1: A quick guide to a genetics conversation
Let’s work from “big” to “small” when talking in terms of molecular genetics. The largest unit is a chromosome. Within each chromosome, there are several genes. Genes are made up of a combination of four bases called: A, G, T, and C. Every gene has a normal sequence, or order, of these bases. These sequences in our genes encode for proteins which make our bodies function. Much like the specific gene sequence, proteins, therefore, also have a normal sequence. Units that make up proteins are called amino acids.
Sometimes, the gene sequence can have mistakes, called variants (or mutations). When there is a change in the gene sequence, it may cause a change in the amino acid sequence of the protein, causing the protein to not function properly. These changes can have varying effects on the gene and protein; some can cause big problems while others don’t have any effect at all.
Whenever we see a change here at Athena, we research that change and assign it a score. The variant score is a reflection of how this change contributes or does not contribute to disease. If the score is low, it is not predicted to have much effect on disease, while if the score is high, it is expected to have a significant effect. Occasionally, data may be unavailable or evidence is conflicting. Therefore, it is uncertain if the mutation is causing a problem or not. This is when it ends up as a variant of uncertain clinical significance. A brief example below may help illustrate how this all fits together. It may also help in reading or discussing a genetics report:
There are different locations within chromosomes where genes are located.
- “21q22.11” is how a chromosome position is written
- It is spoken like this: “Chromosome number 21, on the long arm, at position 22.11”
- “SOD1 gene” (*OMIM 147450) is the name of a gene at this location
An example variant (mutation): c. 131A>G
It is spoken like this: “At position 131 of the coding DNA (gene) sequence (c. stands for coding sequence), the sequence changed from A (normal sequence) to G (abnormal)”. This variant (mutation) causes the amino acid change known as p. 44 HIS>ARG
It is spoken like this: “At position 44 of the protein sequence (p. stands for protein sequence), it changes from HIS (histidine) (normal) to ARG (arginine) (abnormal)”
Stay tuned for more tips and educational modules about genetics concepts and language. We are committed to helping you better understand the complicated world of genetics by providing these mini-tutorials in easy-to-understand language. If there are suggestions, questions or topics you would like to see covered, email the Athena Genetic Counselors at: Genetics@AthenaDiagnostics.com. Don’t be shy, reach out today!