The National Center for Biotechnology Information (NCBI) (Gene database) is an online resource to learn about gene sequences, gene alleles and mutations, genomes, and much more. It was created for the scientific community, but with a little effort and this guide, anyone with a basic understanding of genetics can learn to use it (see Table 3 for a list of resources to brush up on genetics). Following are instructions, tips, and advice on how to get started using this resource.

What can I use the NCBI Gene database for?

The NCBI Gene database has information on gene sequences, gene alleles and mutations, genomes, amino acid sequences for proteins, and much more genetic data on humans, as well as many other animal species. You can explore many resources on the NCBI Gene database. In this tutorial, you will use the database to look up a gene of interest and learn what specific mutations in that gene may cause certain genetic diseases. The end of this tutorial covers additional resources and the NCBI's own tutorials for learning more about other NCBI Gene functions and tools.

How can I look up a gene and find out more information about it?

Watch the video or see the written instructions below for an overview of how to use the NCBI website.

Here we will show you how to look up a gene of interest to learn more about it. For the purpose of simplifying the directions, we will use cystic fibrosis as the example in this tutorial.

1. Go to the NCBI Gene database website. shown in Figure 1. (Note: This link will open a new window so you can more easily follow the steps.)
2. At the top, enter the name of your gene of interest and click "Search."
   1. For example, the gene that is mutated in cystic fibrosis is CFTR. (Note: If you were interested in a disease, but did not know the related gene(s), you could look that up using another Science Buddies resource, the Genetics Home Reference Tutorial.) To look up this gene, enter: CFTR

3. The resulting page, shown in Figure 2, may have a long list of related results. The top results are usually the most relevant ones. You are looking for the first entry that both starts with your gene name and includes the species name for humans (Homo sapiens). In our CFTR example, this is the first result; click on it to proceed to the gene page.

4. The gene page, shown in Figure 3, contains a large amount of information about a given gene.

Use the table of contents (circled in green in Figure 3) to navigate to different information on the gene page. Table 1 gives an overview of the different types of information provided.

Use the "Related information" section (circled in red in Figure 3) to navigate to additional NCBI pages with information on the gene and its role in human biology. Table 2 highlights some of the links that are particularly relevant to learning more about the gene's normal and disease functions.

I want to look up a gene involved in a genetic disease and find out how it is mutated in that disease. How can I do this?

Once you have completed the tutorial section "How can I look up a gene and find out more information on it?", here we will show how to find mutated versions of a gene that cause a genetic disease. For the purpose of simplifying the directions, we will use cystic fibrosis as the example in this tutorial.

1. Once you have located the NCBI Gene page for your gene of interest (step 4), scroll down through the "Related information" section on the right (circled in red in Figure 3) until you see the "Variation Viewer" link (circled in red in Figure 4). Click on this link.

2. A gene can have many different alleles, or alternative forms that occur through mutation of the DNA. Each row of data on this page, shown in Figure 5, lists a different allele for the gene you just searched for.
   1. On the left side of the page you can choose different options to filter the data. Click on "Pathogenic" and "Likely pathogenic" (circled in blue in Figure 5) to sort the alleles according to these criteria. Here are the different clinical interpretations for alleles:
      1. "Likely pathogenic:" Alleles that are thought to be likely to cause disease, but are not proven.
      2. "Pathogenic:" Alleles that have been proven to cause disease.
      3. Alleles for which the "Clinical interpretation" column is blank. There is "no data" for these alleles. These still could be pathogenic.
   2. The other columns on this page can tell you other information about each allele, including variant type and and location of the gene mutation. See Figure 5 for details.

3. Once you have applied all your filter criteria (variant type, clinical significance, etcetera), click on the arrow to the left of the variant ID (circled in yellow in Figure 5 and Figure 6) to open a drop-down window that provides more information on this specific gene variant. Here you will find more allele information, such as the "Transcript change," which lists what the DNA mutation is (circled in green in Figure 6) or the "Protein change" that result from the mutation (circled in red in Figure 6).

4. For each selected allele, click on its "Variant ID" link (circled in blue in Figure 6), to go to a new page with information on that specific allele. This information is part of the (SNP Database ).
   1. For each allele page, scroll down to the section titled "Gene View" shown in Figure 7.
   2. Look where "Residue change" is listed (circled in yellow in Figure 7), and there should be an amino acid mutation that matches the "Protein change" information that was listed with this allele on the previous page, which is circled in red in Figure 6.
      1. For example, the CFTR allele listed in Figure 6 had a protein mutation of "Met1Val" This means that the first amino acid in the protein has been changed from Methionine (abbreviated Met or M) to Valine (abbreviated Val or V). This matches the "Residue change," which is listed as "M [Met] ' V [Val]" at position "1".
   3. What other interesting information is available on the gene?

Where can I find additional help on using the NCBI Gene database?

1. To find basic genetic tutorials, go to the main NCBI Gene page (http://www.ncbi.nlm.nih.gov/gene) and click on "How To" in the top left corner. The tutorials include topics like:
   1. "Genes & Expression"
   2. "Genetics & Medicine"
   3. "Genomes & Maps"
2. To find tips on navigating the NCBI Gene database, go to the main (NCBI Gene page). and under "Using Gene," click on "Gene Quick Start."
   1. Explore the other links under "Using Gene" for additional tips, advice, and tools for finding data in the database.
3. To follow a useful tutorial on using the NCBI Gene database, go to the (main NCBI Gene page), and under the section titled "Getting Started" at the bottom of the page, click on "Training & Tutorials."
   1. From here, click on "Documentation".
   2. Find "Gene" in the list and click on "Factsheet" (on the right) for the NCBI Gene database tutorial.

I do not understand some of the terms or concepts used in the NCBI Gene database. Where can I look up more information?

1. For a glossary of terms used on the NCBI databases, from the (main NCBI Gene page) go to the section titled "Getting Started" and click on "Training & Tutorials."
   1. On the very bottom of the page under NCBI, click on the "Resources list."
   2. Under "N" you will find the "NCBI Glossary," which includes a long list of terms.
2. For information about nomenclature, on the (main NCBI Gene page), look under "Using Gene" for a link to go to the "FAQ" page.
3. To learn more about biology/genetics in general, see Table 3.