View source for FlyBase:Human Disease Model Report

Last Updated: 15 Dec. 2017

This is a field-by-field guide to the information provided in the '''Human Disease Model Report'''.

==General Information==

{| class="wikitable" style="width: 100%;"
|'''Name'''|| style="width: 80%;" | The valid full name that is used in FlyBase for the Human Disease Model.
|-
|'''FlyBase ID'''||  The Primary FlyBase identifier number of the human disease, used to uniquely identify the Human Disease Model in the database. 
|-
|'''Disease Ontology ID'''|| Links to [http://disease-ontology.org/ Disease Ontology] term report in the [http://{{flybaseorg}}/static_pages/termlink/termlink.html Vocabularies] tool.
|-
|'''Parent Disease	'''|| Links to parent entity, which describes general and shared information for the phenotypic series. Specific (child) diseases are usually defined by a single causative human gene.
|-
|'''OMIM'''|| Links to relevant [http://omim.org/ OMIM] phenotype report.
|-
|'''Parent Disease DOID	'''|| Links to [http://disease-ontology.org/ Disease Ontology] term report for the Parent Disease in the [http://{{flybaseorg}}/static_pages/termlink/termlink.html Vocabularies] tool.
|}

==Overview==

The Overview is a brief summary of the ''Drosophila'' human disease model. For specific disease models, it includes (1) the FlyBase disease name, any abbreviation commonly used, and the pattern of inheritance in human (e.g., autosomal dominant); (2) the human gene implicated, with a brief mention of known or postulated function and whether it is implicated in any additional diseases; (3) the Drosophila ortholog(s) of the implicated human gene, the nature of available genetic reagents for that gene, and whether other human genes are orthologous to that fly gene; (4) whether the human gene has been transgenically introduced into flies, the nature of transgenically expressed constructs, whether the human gene has been used to heterologously rescue Drosophila loss-of-function phenotypes; (5) variants implicated in human disease that have been characterized, whether in the context of a transgenic human gene or an analagous mutation in the fly gene; (6) highlights of phenotype(s) of the fly gene and whether genetic and/or physical interaction data are available. Records that do not conform to this pattern include reports for phenotypic series and for induced models (diet- or chemically-induced, for example). The Overview is date-stamped to reflect the last curator update.

==Disease Summary Information==

===Parent Disease Summary===

{| class="wikitable" style="width: 100%;"
|'''Symptoms and phenotype	'''|| style="width: 80%;" | Describes symptoms and phenotypes shared by diseases in the relevant phenotypic series. Entry includes links to outside source, and is date-stamped as to when a FlyBase curator last consulted the source.
|}

===Specific Disease Summary===


{| class="wikitable" style="width: 100%;"
|'''OMIM report	'''|| style="width: 80%;" | Links to relevant [http://omim.org/ OMIM] phenotype report.
|-
|'''Symptoms and phenotype	'''|| Describes symptoms and phenotypes characteristic of the disease. Entry includes links to outside source, and is date-stamped as to when a FlyBase curator last consulted the source.
|-
|'''Genetics	'''|| Describes the genetics of the disease, including causative human gene, and pattern of inheritance. Entry includes links to outside source, and is date-stamped as to when a FlyBase curator last consulted the source.
|-
|'''Cellular phenotype and pathology	'''|| Describes the cellular phenotype and pathology characteristic of the disease.  Entry includes links to outside source, and is date-stamped as to when a FlyBase curator last consulted the source.
|-
|'''Molecular information	'''|| Describes molecular information relevant to the disease, including information about the function of the causative gene, molecular information about mutations in the causative gene, and/or molecular information about mutant isoforms of the causative protein. Entry includes links to outside source, and is date-stamped as to when a FlyBase curator last consulted the source.
|-
|'''External links	'''||  A list of links to external databases and resources providing additional background concerning the disease. These include:

[http://www.genecards.org/ Gene Cards]

[http://www.ncbi.nlm.nih.gov/books/ GeneReviews, NCBI Bookshelf]

[http://ghr.nlm.nih.gov/condition/ Genetics Home Reference (condition)]

[http://ghr.nlm.nih.gov/gene/ Genetics Home Reference (gene)]

[http://ghr.nlm.nih.gov/geneFamily/ Genetics Home Reference (geneFamily)]

[http://www.kegg.jp/kegg/pathway.html KEGG Disease Pathways]

[https://www.ncbi.nlm.nih.gov/medgen/ NCBI MedGen]

[https://www.ncbi.nlm.nih.gov/gene/ NCBI (Entrez) gene]

[http://www.gene2function.org/search/ Gene2Function (human gene)]

[http://marrvel.org MARRVEL (gene)]

[http://www.informatics.jax.org/disease/ MGI Human-Mouse Disease Connection]
|-
|'''Disease synonyms	'''|| A listing of other names, abbreviations, acronyms and terms that have been used to refer to the disease.
|}

==Related Diseases==

{| class="wikitable" style="width: 100%;"
|'''Related human health report(s)	'''|| style="width: 80%;" | Links to the Report(s) of disease(s) that are related to the disease that is the subject of a Human Disease Model Report, but is not a member of the same phenotypic series. For example, the diseases could be related by having the same causative human gene.
|}

===Related Specific Diseases===

{| class="wikitable" style="width: 100%;"
|'''OMIM phenotypic series	'''|| style="width: 80%;" | Links to relevant [https://omim.org/phenotypicSeriesTitle/all OMIM phenotypic series]. An OMIM phenotypic series is a tabular view of genetic heterogeneity of similar phenotypes across the genome.
|}

A table that consists of four columns:

'''Disease''' - Consists of OMIM symbol, links to OMIM phenotype report.

'''Associated Human gene(s)''' - Consists of OMIM symbol, links to OMIM genotype report.

'''Drosophila model''' - Consists of valid full name that is used in FlyBase for the disease, links to Human Disease Model Report.

'''Human transgene in Drosophila''' - "y" or no entry; has the human ortholog been transgenically expressed in flies.

==Ortholog Information==

{| class="wikitable" style="width: 100%;"
|'''Human gene (HGNC)	'''|| style="width: 80%;" | Links to HUGO Gene Nomenclature Committee ([http://www.genenames.org/ HGNC]) symbol report.
|-
|'''Human gene (FlyBase)	'''|| Links to FlyBase [http://{{flybaseorg}}/wiki/FlyBase:Gene_Report Gene Report] of human gene transgenically expressed in flies.
|-
|'''D. melanogaster ortholog (based on DIOPT)	'''|| Links to FlyBase [http://{{flybaseorg}}/wiki/FlyBase:Gene_Report Gene Report] of ''Drosophila'' gene orthologous to HGNC gene. Orthology determined by [http://www.flyrnai.org/cgi-bin/DRSC_orthologs.pl/ DIOPT] analysis resulting from the combined predictions of multiple ortholog prediction algorithms.
|-
|'''Comments on ortholog(s)	'''|| Comments on the nature of the orthology of the human to ''Drosophila'' gene(s), e.g., one to one, one to many, many to one, many to many, as defined by [http://orthodb.org/ OrthoDB] ortholog prediction.
|-
|'''Other mammalian ortholog(s) used	'''|| Links to FlyBase [http://{{flybaseorg}}/wiki/FlyBase:Gene_Report Gene Report] of nonhuman mammalian gene transgenically expressed in flies.
|}

==D. melanogaster Gene Information==
Drosophila gene(s) identified as model(s) of this disease.

{| class="wikitable" style="width: 100%;"
|'''Molecular function (GO)'''|| style="width: 80%;" | A summary of the [http://geneontology.org/ Gene Ontology] [http://geneontology.org/page/molecular-function-ontology-guidelines molecular function] terms associated with the ''Drosophila'' gene orthologous to the causative human gene.
|-
|'''Cellular component (GO)'''|| A summary of the [http://geneontology.org/ Gene Ontology] [http://geneontology.org/page/cellular-component-ontology-guidelines cellular component] terms associated with the ''Drosophila'' gene orthologous to the causative human gene.
|-
|'''Comments on ortholog(s)	'''|| Comments on the nature of the orthology of the ''Drosophila'' to human gene(s), e.g., one to one, one to many, many to one, many to many, as defined by [http://orthodb.org/ OrthoDB] ortholog prediction. Comment concerning protein identity and similarity between Drosophila protein and the human ortholog; alignment determined by [http://www.flyrnai.org/cgi-bin/DRSC_orthologs.pl/ DIOPT] analysis
|-
|'''Orthologs and Alignments from DRSC	'''|| Links to [http://www.flyrnai.org/cgi-bin/DRSC_orthologs.pl/ DIOPT] tool; the H.sapiens (Human) link pre-fills the DIOPT interface with the ''Drosophila'' gene to search for its human ortholog.
|}

==Synthetic Gene(s) Used==

Links to FlyBase [http://{{flybaseorg}}/wiki/FlyBase:Gene_Report Gene Report] of artificial gene transgenically expressed in flies (e.g. a CAG repeat construct or hexanucleotide repeat construct). Such genes have the feature type engineered_foreign_region.

==Experimental Findings==

===Summary===

This section used only for original test-case disease model reports; for most human disease model reports this section is blank.

===Description of Experiments===

{| class="wikitable" style="width: 100%;"
|'''Mammalian transgenics: heterologous rescue	''' || style="width: 80%;" | Free text description of use of human or other mammalian transgene to rescue loss-of-function phenotypes of a mutation in its orthologous ''Drosophila'' gene. A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Mammalian transgenics: transgenic phenotype	'''|| Free text description of phenotypes resulting from tissue-specific transgenic expression of human or other mammalian disease-associated protein, with a focus on disease model relevance. A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Mammalian transgenics: interactions	'''|| Free text description of genetic and/or physical interactions observed between transgenically expressed human or other mammalian protein and Drosophila genes/proteins and/or other transgenically expressed human or mammalian genes/proteins, with a focus on disease model relevance. A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|-
|'''Mammalian transgenics: pertubations and treatments	'''|| Free text description of the effect of chemical or environmental perturbations or treatments on the phenotypes resulting from transgenically expressed human or other mammalian protein, with a focus on disease model relevance. This field is also used to describe drug discovery and/or drug screening experiments. A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Drosophila genes: relevant phenotypes	'''|| Free text description of phenotypes resulting from mutations in or RNAi knockdown of the ''Drosophila'' ortholog of a human disease-associated gene, with a focus on disease model relevance. A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Drosophila genes: interactions	'''|| Free text description of genetic and/or physical interactions observed between the ''Drosophila'' ortholog of a human disease-associated gene and Drosophila genes/proteins and/or other transgenically expressed human or mammalian genes/proteins, with a focus on disease model relevance .A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Drosophila genes: pertubations and treatments	'''|| Free text description of the effect of chemical or environmental perturbations or treatments on the phenotypes resulting from mutations in, RNAi knockdown of, or transgenic overexpression of the ''Drosophila'' ortholog of a human disease-associated gene,, with a focus on disease model relevance. This field is also used to describe drug discovery and/or drug screening experiments. A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Drosophila recombinant constructs: phenotype or rescue	'''|| Free text description of phenotypes resulting from transgenic overexpression of the ''Drosophila'' ortholog of a human disease-associated gene, or of the use of ''Drosophila'' transgene to rescue loss-of-function phenotypes of a mutation in the ''Drosophila'' ortholog of a human disease-associated gene. A listing of genetic reagents used in experiments, linked to relevant [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports], are appended to the end of the statement. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Additional information	'''|| Free text descriptions of experiments that are not covered in other descriptive fields, including but not exclusive to gene expression patterns, experiments conducted in cell culture, details of protein structural domains or gene models, and experiments or observations in other organisms. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|-
|'''Proposed mechanisms	'''|| Free text description of key findings concerning disease mechanism that have been discovered or confirmed in ''Drosophila'' experiments. Every statement is linked to a supporting [http://{{flybaseorg}}/wiki/FlyBase:Reference_Report Reference Report].
|}

==Summary of Physical Interactions==

Information regarding curated physical interactions for the protein and RNA products of the gene. Currently, only interactions involving two D. melanogaster genes are reported. Only pair-wise interactions are reported. Information is imported from existing [http://{{flybaseorg}}/wiki/FlyBase:Interaction_Report Interaction Reports].

==Alleles Reported to Model Human Disease (Disease Ontology)==


Human Disease model data curated using disease terms from the [http://disease-ontology.org/ Disease Ontology]. 

{| class="wikitable" style="width: 100%;"
|-
|'''Models''' || style="width: 80%;" | A table showing any human disease(s) that are being modelled by a given mutant or transgenic allele.  The phenotype(s) being studied must recapitulate some aspect of the human disease for the allele to be considered a model. In some cases, an allele may be expected to produce a disease phenotype but does not. These unexpectedly negative results are also shown. 

The table consists of four columns

'''Allele''' - The alleles of the gene that is being used as a model.

'''Disease''' - Indicates whether or not the allele is modeling the disease ('model of' or ''''DOES NOT''' model') followed by the name of the disease (from the [http://disease-ontology.org/ Disease Ontology]).

'''Evidence''' - If the allele models the phenotype on its own 'Inferred from mutant phenotype' is displayed. If the mutant phenotype is only observed in combination with another allele 'In combination with' is displayed followed by the symbols of other allele(s), with hyperlinks to the relevant allele report pages. Note that any drivers that are required for the expression of transgenic alleles are not listed in this section.

'''References''' - lists the reference(s) that describe the model.

This information is also shown on the individual [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports].
|-
|'''Interactions''' || A table showing interactions of this allele with other disease-causing allele(s)

The table consists of four columns

'''Allele''' - The alleles of the gene that is being used as a model.

'''Disease''' - the nature of the interaction ('exacerbates' or 'ameliorates' and the name of the disease (from the [http://disease-ontology.org/ Disease Ontology]). This column also indicates if the allele is not modifying a disease (prefixed with '''DOES NOT''').

'''Interaction''' - 'modeled by' followed by the symbol of the allele that is modeling the disease, with hyperlinks to the relevant allele report pages. 

'''References''' - lists the reference(s) that describes the model.

This information is also shown on the individual [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Reports].
|}

==Genetic Tools, Stocks and Reagents==

===Sources of Stocks===

{| class="wikitable" style="width: 100%;"
|'''Bloomington Stock Center Disease Page'''|| style="width: 80%;" | Links to relevant [https://bdsc.indiana.edu/stocks/hd/index.html BDSC Human Disease Model page].
|}

===Selected mammalian transgenes===

For human or mammalian transgene(s) used to model this disease, transgenic constructs presented as a table that consists of three columns (below). If there are ten or fewer constructs, all are listed. For larger numbers, a selected sample weighted for availability of stocks, frequency of citations, and more recent citations.

'''Allele''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Report] for the human or other mammalian transgene.

'''Transgene''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Recombinant_Construct_Report Recombinant Construct Report] for the human or other mammalian transgene.

'''Publicly Available Stocks''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Stock_Report Stock Report] for those human or mammalian transgenes available from a public stock center.

===Selected Drosophila transgenes===

For Drosophila gene(s) used to model this disease, transgenic constructs and associated alleles presented as a table that consists of three columns (below). All alleles of transgenic constructs associated with a disease ontology term are listed. Additional listings weighted for availability of stocks, frequency of citations, and more recent citations.

'''Allele''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Report] for the ''Drosophila'' transgene.

'''Transgene''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Recombinant_Construct_Report Recombinant Construct Report] for the ''Drosophila'' transgene.

'''Publicly Available Stocks''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Stock_Report Stock Report] for those ''Drosophila'' transgenes available from a public stock center.

===RNAi constructs available===

For Drosophila gene(s) used to model this disease, all RNAi constructs; presented as a table that consists of three columns:

'''Allele''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Report] for the RNAi construct.

'''Transgene''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Recombinant_Construct_Report Recombinant Construct Report] for the RNAi construct.

'''Publicly Available Stocks''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Stock_Report Stock Report] for those RNAi constructs available from a public stock center.

===Selected Drosophila classical alleles===

For Drosophila gene(s) used to model this disease, alleles presented as a table that consists of four columns (below). All classical alleles associated with a disease ontology term and/or described as amorphic are listed; if no amorphic alleles have been reported, loss-of-function alleles are listed. 
 
'''Allele''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Allele_Report Allele Report] for the ''Drosophila'' classical mutant.

'''Allele class''' - Lists the [http://{{flybaseorg}}/wiki/FlyBase:Controlled_vocabularies_used_by_FlyBase FlyBase CV term] for the allele class to which the allele belongs.

'''Mutagen''' - Lists the [http://{{flybaseorg}}/wiki/FlyBase:Controlled_vocabularies_used_by_FlyBase FlyBase CV term] for the mutagen responsible for the genetic lesion causing the mutation.

'''Publicly Available Stocks''' - Links to the [http://{{flybaseorg}}/wiki/FlyBase:Stock_Report Stock Report] for those ''Drosophila'' classical mutants available from a public stock center.

===References===

A list of publications that discuss the human disease model, subdivided into fields by type of publication.