NCBI Gene: Variations (Part 1): Disease-Causing Variants

The NCBI Gene database includes and links to information about genetic variation, including the results of studies that link diseases and conditions (phenotypes) to specific genetic variations.

This tutorial demonstrates how to answer the following question using the NCBI Gene database:

What variations are present in the gene and are they associated with disease?

In this first part, we'll answer the question:

What diseases can be caused by variations in the tyrosine hydroxylase gene?

Step 1: In the NCBI Gene Database, search for human tyrosine hydroxylase:

tyrosine hydroxylase AND human[orgn]

Sort by Relevance.

When you sort by relevance, usually the record of interest appears at the top. In this case, we're interested in the human tyrosine hydroxylase (TH) gene.

Step 2: Click on the TH (ID: 7054) record link.

Now that we've found the right gene, we want to find the diseases associated with it.

Step 3: Go to the "Phenotypes" section in the Table of Contents.

What is a phenotype?

There are two parts to the Phenotypes section: Associated Conditions and EBI GWAS Catalog.

Let's look at each of these.

Look at the Associated Conditions section.

The Associated Conditions may include diseases directly caused by changes in this gene. In this case this gene is associated with Autosomal recessive DOPA responsive dystonia which includes Parkinson-like symptoms due to a deficiency of L-Dopa.

The MedGen article (link for C2673535) provides a literature review of disease characteristics plus summaries from other sources such as GeneReviews, OMIM and Genetics Home reference.

Look at the EBI GWAS (Genome-Wide Association Study) Catalog section.

What is a genome-wide association study?

The GWAS Catalog results describe association or linkages of phenotypes with variants in or near the gene. These may or may not be causative. For example, the publication "Genome-wide association scan for variants associated with early-onset prostate cancer" (PMID: 24740154) reports on a significant association between early-onset prostate cancer and a variant in the chromosome 11p region near the TH gene.

In the next part of this tutorial, we'll explore how to find variants that affect the coding region.

Close both windows to end the Guide.