Hidden genes: do they make finding diseases harder?

Ryan, N.M., Corvin, A. Investigating the dark-side of the genome: a barrier to human disease variant discovery?. Biol Res 56, 42 (2023). https://doi.org/10.1186/s40659-023-00455-0

Some parts of our genetic code are like puzzles that current technology can't solve very well. This study explores how these puzzle-like parts affect our ability to find genes related to diseases. It suggests they make it harder to discover these genes.

Genome studies have found areas related to diseases but struggle to pinpoint the exact gene changes causing them. Some genes seem linked to diseases based on various research methods, but when we look at their genetic makeup, we don't find clear evidence of disease-related changes. We're not sure if these genes are wrong leads or if something else is causing this.

As we learn more about our genetic code, we've found that some parts are hard to read with current technology. These tricky areas are called "dark regions" because they are challenging to map out. Depending on how we define them, they could make up a substantial portion of the genome. This might explain why we're having trouble finding disease-related gene changes because some of these genes could be in the dark regions.

Until now, no one has really explored how those hard-to-read genetic areas (known as dark regions) might affect our ability to find disease-related gene changes. This study aimed to see if these dark regions could impact our ability to discover disease-related gene changes in different diseases and traits.

They looked at eight different health conditions like autism and schizophrenia and checked if the genetic regions linked to these conditions had dark areas. Turns out, in these eight cases, around one-third to three-quarters of these regions did have some dark areas. These dark areas varied in size from really tiny (in autism) to quite large (in schizophrenia and body weight). Additionally, a small portion of the genes in these regions also overlapped with dark areas, and some of them even had dark protein-coding parts.

In simple terms, when studying genes related to diseases, some of them have tricky parts called "dark regions" that current technology can't read well. However, not all genes linked to diseases are expected to play a significant role in causing the disease. To see if these tricky genes in dark regions are still relevant, scientists looked at their functions.

They found that genes in these dark regions were related to the diseases they were studying. For example, genes related to schizophrenia, body weight, and depression had important roles in those conditions. This suggests that these genes in dark regions might contain key information about the diseases.

They also looked at rare gene changes related to diseases and found that some of these changes were in the dark regions. This means we might be missing important genetic clues about diseases because of these tricky areas in our genes.

Researchers have discovered that certain "dark genes" hidden in our DNA play a role in many diseases, especially those affecting the brain and nervous system. This study supports this finding and suggests that there are likely more of these dark genes linked to neurological disorders than we've currently identified. The study also acknowledges that the number of these dark regions can vary based on the technology and genetic code version used. Longer genetic readings work better for identifying these regions, and different genetic code versions can affect their prevalence.

The study used data from genetic studies (GWAS) to show that these dark regions often overlap with areas strongly associated with diseases. In some cases, these regions cover a significant portion of the genetic code linked to diseases. This means that these dark genes likely have a substantial role in disease risk, and overlooking them can lead to incomplete understanding.

In summary, this study highlights the importance of understanding and addressing the impact of dark regions in our genetic code on disease research. It suggests that there may be many more dark genes related to diseases, particularly neurological ones, than we've realized. To advance our knowledge, researchers should consider using advanced sequencing technologies to unlock the secrets hidden within these dark genes.

By Lia Lalkaka