How to: Find human variations associated with a phenotype or disease (clinical association)

Starting with a disease or phenotype in...

PubMed

  1. On the PubMed homepage, search with a disease or phenotype name and additional terms to find variations that have been identified as being associated with or causative for the phenotype, for example:  humans[MeSH terms] AND asthma AND (causative OR associated OR association) AND (variation OR variant OR mutant).
  2. Alternatively, on the PubMed Clinical Queries page you can search for medical genetics publications.  Perform a search on this page and link to "See all" records at the bottom of the Medical Genetics column (on the right).

OMIM

  1. On the OMIM homepage, enter the disease or phenotype name in the search box.
  2. Click the Limits tab and click the check box for "Allelic Variants" in the section "Only Records with:".
  3. Click the Go button.
  4. Click the OMIM number of the desired phenotype/disease record to open the full display.  Note: You will be redirected to omim.org.
  5. In the "Text" section there may be a description of a gene or genes that have been identified as having an association with the phenotype/disease.  Links for each gene will display the gene-specific page. 
  6. Clicking on "Table of Contents" on the upper right will open a list of section headers, including "Allelic Variants" and "Table View".  Clicking on "Table View" displays a summary of the variants, associated phenotypes, with an rsID number if the variant has been registered in dbSNP. Clicking the rsID will display the SNP record at Ensembl for summary information on the variant. This page has a link near the top to go to the pertinent dbSNP page for more information and links to NCBI resources.

dbVar

  1. On the dbVar homepage, enter a disease  or phenotype name by typing in the search box.
  2. Click Limits under the search bar.
  3. In the “Clinical interpretation" section, select "Pathogenic" and "Uncertain Significance: likely pathogenic" by clicking the check boxes.
  4. Click the Search button.
  5. Click the “Variant” filter at the upper right (to exclude the report of the study registered in dbVar).
  6. Click any nsv identifier for more information and links to other NCBI resources.

PheGenI

  1. On the PheGenI homepage, select a Category or Trait name in the "Phenotype Selection" section.   Selecting the "Category" first will limit the list of Traits to those available for the particular MeSH Category.
  2. To limit the retrieval of data by P-Value of the association report, enter the exponent in the box.
  3. Click the Search button.
  4. Click "Association Results" in the Search results section to review the data in the Association Results table to evaluate the evidence for the association between a variation and the measured trait.  For more and related information, click links to the "Gene", "PubMed", or "Source" databases.
  5. Alternatively, click "Genes" in the Search results section to review the genes associated with the phenotype selection.  Click a Location link to see an interactive graphical sequence viewer display for the selected gene.

Gene and linking to dbSNP

  1. On the Gene database homepage, enter a disease or phenotype name in search box and click "Search".
  2. On the right-hand side of the page, scroll down to find the "Find Related Data" section.  Click the "Database" pull-down menu, select "SNP" and then click "Find items".  This temporarily saves a search for "SNP Links for Gene" in your "History".
  3. On this SNP database page, clear your search term and click the Limits tab.  Scroll down to the "Annotation" section and click  "Clinical/LSDB Submissions" and under "Clinical Significance" click "pathogenic" and "probable pathogenic".  Click the "Go" button on the top of the page to run and save a search for "Search Limits: snp_gene_clin, pathogenic, probable pathogenic" in your "History".
  4. Just under the search box, click the "History" tab.  Find the number in front of the two searches described in steps 2 & 3.  Type the numbers into the search box above with a capitalized AND in between, for example:  #2 AND #6 .
  5. Click Go button to retrieve the list of variants with summary information.
  6. In this view, each variant will display a graphic that may show a yellow button displaying "OMIM".  Click this button to find more information regarding the phenotype/disease associated with this particular variant.