Using the Human - Mouse: Disease Connection

This help document answers the following questions:

What can I use the Human - Mouse: Disease Connection (HMDC) Form to find?

Use this query form to find phenotype and disease associations for human and mouse genes and genome regions. You can enter a combination of multiple phenotype terms, disease terms, gene symbols, accession identifiers (IDs) and genome coordinates.

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How does MGI define phenotype, disease, and allele?

phenotypeA description of the observable state of an individual with respect to some inherited characteristic. See also dominant and recessive in the MGI Glossary.
disease A human disease, syndrome, or condition listed in the OMIM (Online Mendelian Inheritance in Man) database.
alleleOne of the variant forms of a gene, differing from other forms in its nucleotide sequence. Allele category, allele combination and allele pair also appear in the MGI Glossary.
allele nameIn MGI, an allele name is a word or phrase that uniquely identifies an allele of a given gene. The allele name has an abbreviation that is the allele symbol added as a superscript to the gene symbol. See also Gene Name in the MGI Glossary.
allele symbolIn MGI, an allele symbol is a unique abbreviation for the allele name of a given gene. Allele symbols take the form of superscripts added to the gene symbol. See also Gene Name and Gene Symbol in the MGI Glossary.
allelic composition
(genetic background)
See Allele Combination in the MGI Glossary.

Note: Some terms may have unique definitions in the context of MGI queries and results. For more information, see:

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How do I use this query form?

Choose a field to search by toggling "Please select a field."

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What values are acceptable in each of the fields?

Search by: Gene Symbol(s) or ID(s) | Gene Name | Phenotype or Disease Name | Phenotype or Disease ID(s) | Genome Location | Gene File Upload

FIELD DESCRIPTION
Gene Symbol(s) or ID(s) Symbol, synonym, vertebrate homolog or ID for a human or mouse genetic marker.
  • Enter one or more markers, separated by commas. Be aware that some IDs use prefixes (e.g. MGI:, HNGC:). Prefixes make IDs unique.
  • Unlike most MGI search forms, the asterisk (*) is NOT supported as a wild card. To find phenotypes and diseases associated with a family of genes, such as fibrillins, use the Gene Name field.
  • If you wish to upload a file of a column of comma, semicolon or tab separated list gene symbols or IDs, use the Gene File Upload field.
Gene Name Name or synonym for human or mouse genetic marker. If you enter more than one word, this field automatically ANDs them. A search for paired box finds genes with names that contain both paired and box.
Phenotype or Disease Name The Search by disease or phenotype terms section is a full-text search field.
  • Begin typing a term of interest and an autocomplete list activates on the first character.
    • The list shows all the OMIM, Human Phenotype Ontology (HPO) and Mammalian Phenotype (MP) vocabulary terms and their synonyms that match your search characters.
    • You can type the beginnings of multiple terms to narrow the list (example: congest heart).
  • Choosing a term includes results for its subterms. For example, selecting abnormal pulmonary pressure also includes results for its subterms, increased pulmonary artery pressure and decreased pulmonary artery pressure.
  • After you select a term, you can click the Add button to repeat the process to add additional terms. The default Boolean will AND the terms together. Use the toggle if you wish to OR the terms.
  • You do not have to select a term. Free text searching is permitted in this field.
  • If you are unsure of the proper terms to use, use free text (don't select a term) or use the appropriate browser to find vocabulary terms and their definitions:

Phenotype or Disease ID(s) IDs from the Mammalian Phenotype (MP) Ontology, Human Phenotype Ontology (HPO) or Online Mendelian Inheritance in Man (OMIM). Be aware that the MP and HPO IDs use the prefixes: MP: and HP:.
Genome Location You can enter a mouse or human genomic region (e.g. 2:105668896-108698410 or chr13:22210730-22311689) and use the radio button to specify the species (Mouse or Human). Use MT for the mouse mitochondrial chromosome.
  • You can search with a Chromosome (e.g. 19 or 19: or chr19) but not by chromosome arms or bands. So human chr:7p22 won't return any results. The form will only accept a digit following the chromosome.
  • To search for multiple regions, use the Add button. Note the default Boolean, AND, will return results for genes that are shared in all your search regions. To return results for genes in each region, toggle AND to OR.
Gene File Upload Upload a column of gene symbols and/or their IDs. To do so, follow these steps:
  1. Toggle "Please select a field" to "Gene File Upload."
  2. Click the Choose File button to browse your computer and select a file to upload.
  3. Toggle the Column Number to choose the column of gene symbols or IDs in your file that you wish to use to search the HMDC.
  4. Indicate the Delimiter for your file: Tab, Semicolon, or comma.
  5. You can check the box to Ignore the Header Row.
  6. Click the Search button.

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Is there a list of phenotype terms to select from?

Yes. The mammalian phenotype terms are from the Mammalian Phenotype (MP) Ontology, a community effort to provide standard terms for annotating phenotypic data. The Mammalian Phenotype Ontology has a hierarchical structure that permits a range of detail from high-level, broadly descriptive terms to very low-level, highly specific terms. This range is useful for annotating phenotypic data to the level of detail known and for searching for this information using either broad or specific terms as search criteria. You can either browse or search the Ontology with the Mammalian Phenotype Browser. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated phenotype data at MGI are provided in Term Detail reports. See Using the Mammalian Phenotype (MP) Browser for additional help.

The HMDC also searches the Human Phenotype Ontology (HPO). The HPO provides a standardized vocabulary of phenotypic abnormalities encountered in human disease. You can search the HPO vocabulary directly with the HPO web browser.

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Is there a list of disease terms to select from?

Yes. The disease vocabulary contains human disease, syndrome, and condition terms from Online Mendelian Inheritance in Man (OMIM). You can browse the vocabulary and find links to full OMIM records and mouse model information by using the Human Disease Vocabulary Browser. Navigate the vocabulary until you find the term you are looking for. See Using the Human Disease Vocabulary Browser for additional help.

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Can I query using both a phenotype term and a disease term?

Yes, you can use the Phenotype or Disease Name or the Phenotype or Disease ID(s) fields to search for phenotypes and/or diseases. Choose the appropriate Boolean term, AND or OR, for your search.

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Can I edit my original options and requery?

Yes, you can.

Notes:

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How do I interpret the query results?

Your search results are displayed within three tabs: Gene Homologs x Phenotypes/Diseases, Genes and Diseases. The Gene Homologs x Phenotypes/Diseases grid only displays genes with phenotype and disease associations. With all searches, the Gene Homologs x Phenotypes/Diseases tab is the default selection.

Gene Homologs x Phenotypes/Diseases

The Gene Homologs x Phenotypes/Diseases tab, the default selection, provides an overview of your results in a grid format. The query summary contains the following fields:

Human Gene Symbol of the gene, linked to homology information.
Mouse Gene Symbol of the gene, linked to its MGI gene detail record.
Phenotypes And Diseases Starting from the left are high level terms from the Mammalian Phenotype (MP) Ontology for which there are either annotated alleles of the mouse gene or human genes associated with with similar phenotypes through the Human Phenotype Ontology (HPO). See also the Mammalian Phenotype Browser and the HPO web browser. Phenotypes that are only annotated to complex mouse genotypes—those involving more than one genome feature—are not listed in this summary. Phenotypes to all the genotypes associated with an allele can be viewed by following allele symbol links to Allele Detail pages. Listed to the right, after a vertical grey bar, are human diseases associated with the human gene in OMIM or through mouse models described in publications. The Gene Homologs x Phenotypes/Diseases grid only displays genes with phenotype and disease associations. To see all the genes associated with your search, click on the Genes tab.

Human and mouse phenotype annotations are returned and are indicated by the colors, blue for mouse data and tan for human data.

Some of the human disease terms have been shortened but if you hover your cursor over the term, a pop-up will display the full term name. Highlighted column titles indicate which columns contain phenotype or disease terms that match one or more terms in the search. Highlighting is only displayed on column titles, and only when a phenotype or disease term is used in the search. A column is highlighted when at least one of the genes has an annotation matching your search. So if you search for a general term such as fibrosis, the cardiovascular system column may be highlighted because one gene is associated with cardiac fibrosis. Another gene may not have cardiac fibrosis but is returned because it is associated with pulmonary fibrosis, causing the respiratory system column to be highlighted. Columns that are not highlighted contain additional phenotypes and/or disease terms associated with the mouse model or human gene that is connected to the searched term(s).

The colors, blue for mouse data and tan for human data, get progressively darker with more supporting annotations. The lightest color represents one annotation. 2-5 annotations is represented by a darker shade, 6-99 annotations darker still and more than 100 annotations by the darkest color.

You can hover your cursor over a colored square to see that row's markers and column heading in a pop-up.

The grid contains its own scroll bars, though you may have to move your cursor to the bottom or right edges to make them appear.

Click on a blue colored square for information on mouse genotypes and lower level phenotype terms. The mouse genotypes link to even more detailed phenotype information. Click on a tan colored square for information on the human disease and human phenotypes associated with the human gene.

A bold N in a phenotype column indicates that no abnormal phenotypes of that type were observed in any allele of the gene.

You can filter the grid to show only specified columns and rows by clicking on the Filter by Genes or Filter by Phenotypes button and checking the appropriate criteria and clicking the Apply Filters button.

Genes

If you select the Genes tab, the query summary contains the following fields:

Organism States whether the corresponding marker is human or mouse
Gene Symbol Symbol of the gene. Mouse genes are linked to their MGI gene detail records. Human genes are linked to their Vertebrate Homology Class pages. Vertebrate Homology Class pages provide links to Entrez Gene and the ability to download sequences in FASTA format for several vertebrate species.
Genetic Location The chromosome and genetic map position for the marker are shown if known.
Genome Coordinates The marker's chromosome basepair coordinates, strand and genome build are shown if known.
Associated Human Diseases Lists any human diseases described in Online Mendelian Inheritance In Man (OMIM) that are associated with the marker. Disease associations for human markers are from the NCBI mim2gene_medgen file and include annotations from OMIM, NCBI curation, Gene Reviews, and Gene Tests. Mouse markers are associated with human diseases through genotypes described in publications.
Abnormal Mouse Phenotypes Reported in these Systems High level terms from the Mammalian Phenotype (MP) Ontology annotated to alleles of the mouse gene. See also the Mammalian Phenotype Browser. Phenotypes that are only annotated to complex genotypes—those involving more than one genome feature—are not listed in this summary but can be found in the Phenotypic Allele Detail Report.
References For mouse markers, a link to all the references for the marker is provided. A separate link may be present that links to the just the disease relevant references. The reference summary provides the abstract and links to MGI curated data and when possible, links to PubMed and Journals.
Mice With Mutations In this Gene (IMSR) Shows the number of stocks in the International Mouse Strain Resource (IMSR) that contain an allele of the gene. The number links to the IMSR which provides access to stock repositories.

The default sort for this tab is by Marker Symbol, though you can choose to sort by any column by clicking the column headings or the up/down arrowheads ( ▼ ▲).

Diseases

If you select the Diseases tab, the query summary contains the following fields:

Disease The OMIM disease term linked to the MGI Human Disease and Mouse Model Detail page
OMIM ID The Online Mendelian Inheritance In Man (OMIM) accession ID
Mouse Models The number of mouse models for this disease, linked to Mouse Model details.
Associated Genes from Mouse Models The mouse markers used to create the various models of this disease
Associated Human Genes Human genes associated with the disease. Disease associations for human genes are from the NCBI mim2gene_medgen file and include annotations from OMIM, NCBI curation, Gene Reviews, and Gene Tests.
References using Mouse Models The number of references describing mouse models of the disease, linked to reference details and curated data

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What phenotypes and diseases are searched and displayed in the HMDC?

Phenotypes and diseases for mouse genes are limited to those where mutations in only a single gene or introduction of a single transgene are believed to be causing the phenotype. Phenotypes and diseases resulting from multiple mutations or transgenes are excluded. For details, see: Bello SM, Eppig JT, and the MGI Software Group. 2016. Inferring Gene-to-Phenotype and Gene-to-Disease Relationships at Mouse Genome Informatics: Challenges and Solutions. J Biomed Semantics 2016. 7:14. Human diseases are limited to those in OMIM. Human phenotype annotations are limited to those in the HPO-to-OMIM annotation set. Phenotypes and diseases without gene associations may be searched but will not be displayed on the Gene Homologs x Phenotypes/Diseases tab.

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How do I filter my results?

You can filter any of the tabbed result views. In your results, click the Filter by Genes and Filter by Phenotypes/Disease(s) and check the desired criteria by clicking on them. For long lists of results, you can use the Search field within the Filter. This will launch an autocomplete on the second character. When you have finished making your selections, Click the Apply Filters button. This will reduce your results to only those containing the checked items. The filters are applied across all data tabs and to any file you export. Your filter options are limited to those displayed in the Gene Homologs x Phenotypes/Diseases tab. Use the Remove Filters button to remove all filters and return to your original results.

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Are there different ways to view the output of my query?

Yes.

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Can I get my results as a tab-delimited text file?

Yes. The Genes and Diseases tabs but not the Gene Homologs x Phenotypes/Diseases tab, provide a tab-delimited text export option. In your search results, click on the Text File icon. Your web browser will download a file of the results.

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What are some examples of queries?

For some basic searches, see Human - Mouse: Disease Connection (HMDC) Search Examples.

  1. I have a list of human genes and Entrez Gene IDs of interest. How can I find phenotypes and diseases associated with their mouse homologs?
    Paste your list as a column or separated by commas or spaces into the Search by: Gene Symbol(s) or ID(s) field. For example: APP, PLAU, PSEN1, CAV1, NOS3, 10513

    Click the Search button.

    The search finds matching mouse and human genes and synonyms, and their homologs and associated mouse transgenes, and displays phenotypes associated with allele pairs of the mouse genes and transgenes, phenotypes associated with the human gene and diseases associated with both the human and mouse markers.

  2. I am interested in finding genes associated with Alzheimer Disease in humans and in the mice used to model the disease. How can I do this?
    1. Toggle "Please select a field" to "Phenotype or Disease Name."
    2. Start typing alzheimer and select either Alzheimer or Alzheimer Disease from the list that appears. If you are interested in a particular type of Alzheimer Disease, then select it from the list. If you wish to include more types, click the Add button and repeat the process and remember to change the default Boolean from AND to OR.
    3. Click the Search button.

    The broadest search finds all diseases and their synonyms that contain the word, Alzheimer, and returns all human genes associated with the disease and mouse genes and transgenes used to model the disease. The grid also displays phenotypes and diseases associated with these mouse genotypes, some of these will have no association with Alzheimer Disease. You can filter the grid to show only specified columns and rows by clicking on the Filter by Genes or Filter by Phenotypes button and checking the appropriate criteria and clicking the Apply Filters button. This also applies the filters to both the Genes and Diseases Tabs.

  3. You are interested in regions of two human chromosomes. How can you see phenotypes and diseases associated with genes in these regions?
    1. Toggle "Please select a field" to "Genome Location."
    2. Select the species and build: Human (GRCh38).
    3. Enter the region: 19:43341000-44910000
      (This format is also supported: Chr19:43341000-44910000)
    4. Click the Add button.
    5. Toggle the second "Please select a field" to "Genome Location."
    6. Select the species and build: Human (GRCh38).
    7. Enter the region: 21:25001000-26971000
    8. Toggle the default Boolean from AND to OR.
    9. Click the Search button.

    The search finds human genes mapped to those regions and returns them, their mouse homologs, and phenotypes and diseases associated with all the returned genes.

  4. I have filtered my search results and now have a list of interesting mouse genes. How can I find functional information for the mouse genes?
    1. Click the Export: Text File button.
    2. Open the file in your spreadsheet software application and copy either the Marker Symbols or IDs.
    3. Direct your web browser to the MGI Batch Query and paste the markers into the text field.
    4. Check the Gene Attributes you wish to see in your results.
    5. In the Additional Information section, select Gene Ontology (GO) to find functional information.
    6. Click the Search button.

    The results show GO IDs and terms that describe the biological processes, molecular functions and cellular components of the gene products. The Batch Query only provides data for mouse genes. If you searched with human gene symbols, synonyms or IDs, the search will return data for their mouse homologs.

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