VarioML Core Ontology Specification

June 2011

This version:

https://svn.gene.le.ac.uk/gen2phen/trunk/data_formats/xml/html/LSDB_spec.html

Latest version:

https://svn.gene.le.ac.uk/gen2phen/trunk/data_formats/xml/html/LSDB_spec.html

Last update:

Date: 06/06/2011

Revision:

Revision: 1.0

Contact:

Juha Muilu - FIMM

Editors:

Name - Gen2Phen

Name - Institution

Contributors:

See acknowledgements.

Copyright © 2007-2011 by Gen2Phen

Development of VarioML Data format has been supported by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 200754 - the GEN2PHEN project

This work is licensed under the GNU GPL.

Table of contents

1. Introduction
2. Background
3. Standards
• Namespace
• Schemata
• Validation services
4. Overview
5. VarioML Examples
6. VarioML Extensibility: Variant Report
• VREPORT-XML Examples
7. VarioML classes and properties cross-reference
   • Vario Properties
   • Groups
   • Schema Document Properties
   • Global Declarations
   • Global Definitions
8. Glossary
9. External Classes and Properties
10. Acknowledgements
11. References
12. Change log

Introduction

The VarioML data format supports data exchange between locus specific databases (LSDBs) and central repositories, in the context of high-throughput (HTP) bioinformatic data flows. Use cases include exchanging data between partners in the context of specific phenotype extensions. External invited participants from the epidemiology, medical genetics, ontology development and model organism communities provided expertise and use cases beyond those of Gen2Phen Partners.

Validation of this LSBD data model commenced in 2009 by working with the existing LSDBs inside and outside the GEN2PHEN consortium, most of whom have existing data formats. This document describes XML and MAGE-TAB based data formats developed from the data model. The VarioML format complements the format developed for the Locus Reference Genomic sequence (LRG) by providing detailed descriptions for variant and individual (patient, or other source of genetic data) information, as defined in Gen2Phen workshops and subsequent community consultations. The MAGE-TAB format is meant for simple spreadsheet-based data entry, covering a core set of VarioML information defined in XML.

The complex integration of data from patients to alleles is organized and standardized, using groups to further simplify research that uses and adds to the growing resources available over the net. Abstract classes are used to make the VarioML format compatible with other ontologies in use around the world.

Future plans include a tabular "light" format, based on the XML format described here, for use by genome browsers such as Ensembl.

Background

The VarioML format is managed as a collaborative effort among members of the Gen2Phen consortium, funded by the Health Thematic Area of the Cooperation Programme of the European Commission within the VII Framework Programme for Research and Technological Development. The name "VarioML" is an acronym for "Locus Specific Database".

More resources on LSDBs are available at the Gen2Phen project site.

The Gen2Phen Web Services and Exchange Formats group is the main discussion list for questions about the VarioML format.

The remainder of this specification describes how to publish and interpret descriptions such as these on the Web, using XML for syntax (file format) and terms from VarioML. It introduces a number of classes (concepts such as variant and exon) and properties (relationship and attribute types such as DNA structure and transversion). The specific contents of the VarioML Core Ontology are detailed in the VarioML Core Ontology Namespace document.

This specification uses the XML format for ease of adoption, but has been designed with awareness of the growing importance of VarioML data becoming available in Linked Data/RDF form. This document has been structured to easily be adaptable to RDFized VarioML data.

For more information, see:

• VarioML website
• Gen2Phen Knowledge Center
• Gen2Phen web services and exhange formats wiki
• Gen2Phen Semantic Web wiki

Standards

The VarioML data format merges data models and expertise from epidemiology, medical genetics, ontology development and model organism communities. The most recent step in developing this standard is the inclusion of Mauno Vihinen's Variation Ontology.

This document presents VarioML as a Semantic Web vocabulary or ontology. It describes the VarioML Core Ontology and the terms (XML classes and properties) that constitute it, so that Semantic Web applications can use those terms in a variety of XML- and eventually RDF-compatible document formats and applications. The VarioML Core Ontology is straightforward, pragmatic and designed to allow simultaneous deployment and extension, and is therefore intended for wide scale use.

The VarioML ontology is identified by the namespace URI:
VarioML:namespace:http://gen2phen.org/VarioML/1.0

Note that ordering of XML classes is significant in formats, e.g. to ensure accurate multiplicity relations. Properties can occur in any order. See here for ordering of classes. Class names are capitalized; property names are lower-case.

• lsdb.rnc
• vreports.rnc

Relax files can be used with any RelaxNGC validator (currently Jing has been tested).
Autogenerated XML-Schema (XSD) definitions are also available. Autogeneration is done using Oxygen tool, which uses the open source Trang schema converter. The XML-schema can be downloaded here: :

• lsdb.xsd
• vreports.xsd.

1. Validate XML made with the VarioML spec here
2. Validate RDF made with the VarioML spec here
3. Example: validation of sample VarioML submission
   Example submission is here

Overview

VarioML Exchange Format

The VarioML core ontology is expressed as an XML schema using the RelaxNG-compact schema definition language, following implementation patterns used in the LRG XML format. This format is based on a minimum information checklist being developed in Gen2Phen workshops, available here.

Figure 1: Overall description of the format, in an individual-centric implementation

Description of the format

Given an individual-centric use case, the overall structure is shown in Figure 1. The format has a single root element LSDB:, with the following sub elements:

• The source element group provides data source information such as database name, contact person(s), etc. There can be multiple source elements, since data can originate from multiple sites.


• The individual element describes the phenotype of the individual using optional ontology terms and optional references to detailed phenotype descriptions, which are defined outside the VarioML format.
  The individual element has one or many variant elements.


• The variant element group specifies mutation specific information, from DNA to RNA and aminoacid levels, using variant elements embedded recursively in the seq_changes element.
  The top-level variant element, if known, is always on the genomic DNA level, otherwise RNA information is used.
  The variant element also has the optional aliases element, specifying variants typically named using a different coordinate system or naming scheme.

VarioML has been designed to serve the spectrum of data exchange needs for variant data, which may be individual-, variant-, or population centric. Separate schema instantiate the VarioML core ontology seperate schema for these needs.

The LSDB-XML format is individual-centric, where the individual can be a patient or other source of genetic data, for locus specific and clinical databases. However, there is also a need for VarioML data exchange in a variant-centric format, for variant reports on population frequency levels. The VREPORT-XML module, described below, provides a simple adaption of the VarioML format for this purpose.

VarioML LSDB-XML Format Examples

Variant Submission Example

<variant type="cDNA">
            <gene source="HGNC" accession="COL1A1" />
            <ref_seq accession="NG_007400.1" />
            <name scheme="HGVS">c.579delT</name>
            <genetic_origin term="paternal">
                <evidence_code term="inferred"/>            
            </genetic_origin>
            <sharing_policy type="openAccess">
                <embargo_end_date>2002-12-12</embargo_end_date>
                <use_permission accession="CC0" uri="http://creativecommons.org/publicdomain/zero/1.0/" 
term="Creative commons"/>
            </sharing_policy>
                        
            <comment>
                <text>Variant inherited from affected father</text>
            </comment>                    
        </variant>

LSDB-XML Basic Submission Example: Individual Level Data

<lsdb id="submission1" schema_version="2.0" xmlns="http://gen2phen.org/varioml/2.0"
    xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
    xsi:schemaLocation="http://gen2phen.org/lsdb/2.0 file:gen2phen/trunk/data_formats/xml/lsdb.xsd"> 
     
    <source id="fimm"> 
        <name>Insitute for Molecular Medicine Finland (FIMM)</name> 
        <contact> 
            <name>J. Muilu</name> 
        </contact> 
    </source> 
                
    <individual id="id1"> 
        <gender code="1"/> 
        
        <variant id="id3"> 
            <ref_seq accession="XYZ"></ref_seq> 
            <name  scheme="HGVS"> c123C>G </name> 
        </variant> 
        <variant id="id5"> 
            <ref_seq accession="XYZ"></ref_seq> 
            <name  scheme="HGVS"> c123C>G </name> 
        </variant> 
    </individual> 
    
    <individual id="id7"> 
        <gender code="9"><description term="XX-male"/></gender> 
        <variant id="id9"> 
            <ref_seq accession="XYZ"></ref_seq> 
            <name scheme="HGVS"> 
                c123C>G
            </name> 
        </variant> 
    </individual> 
       
    <comment><text>simple comment</text></comment>
    

    <comment source="example_ontology" term="example term"><text>my defined comment</text></comment> 
    <comment><text>what ever</text><comment><text>my structured comment</text></comment></comment> 
    

    <comment>
    <text>what ever...</text>
    <comment><text>my complex structured comment</text>
    <evidence_code term="something"/><db_xref accession="xyz"/>
    </comment></comment> 
    
    
</lsdb>

NB: Gender codes are 0: 'unknown', 1: 'male', 2: 'female' and 9: 'not applicable'.

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LSDB-XML Submission Example: Individual Level Data

A more detailed example of a VarioML submission:

<lsdb  id="submission0001" xmlns="http://gen2phen.org/varioml/2.0"
        xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"  xmlns:my="example.org"
        xsi:schemaLocation="http://gen2phen.org/lsdb/1.1 
file:/Users/muilu/Documents/Dev/SVN_repos/gen2phen/trunk/data_formats/xml/lsdb.xsd" >
        <source id="AIREBase" version="1.3"  date="2008-08-21" 

uri="http://www.uta.fi/imt/bioinfo/AIREbase/">
                 
                <name>AIREBase</name>
                <url>http://bioinf.uta.fi/xml/idr/ff/FF72.xml</url> 
                <contact>
                        <name>Mauno Vihinen</name>
                        <address>Institute of Medical Technology, FI-33014 
University of Tampere, Finland</address>
                </contact>
                <acknowledgement>
                        <name>Tampere University Hospital Medical Research Fund</name>
                </acknowledgement>
                <acknowledgement>
                        <name>European Union</name>                        
                        <grant_number accession="EXAMPLE00001"/>
                </acknowledgement>
                <comment><text>Autoimmune polyglandular syndrome type 1 database</text></comment>                
        </source>
        <individual id="A0176"> 
                
                <gender code="2"/>
                <original_id accession='A0176'><comment><text>patient 11</text></comment></original_id>
                <phenotype term="Autoimmune polyglandular syndrome type 1" accession="240300" source="OMIM"/>
                
                 
                <population term="Caucasoid"  type="ethnic"></population>
                <population term="Poland"  type="region"></population>
                
                <variant id="1" type="DNA">
                   
                     
                        <gene source="HGNC" accession="AIRE"/>                        
                        <ref_seq accession="D0003"/>
                        <name scheme="HGVS"> g.4707A&gt;T </name>
                        <exon>1</exon> 
                        <seq_changes>
                                <variant id="1.2" type="RNA"> 
                                        <ref_seq accession="C0003"/>
                                        <name  scheme="HGVS">r.1a&gt;u</name>
                                        <consequence term="frameshift of translation">
                                                <evidence_code term="prediction"/>
                                                <comment><text>


predicted to change of start codon to position c.268,
resulting in a frameshift of translation


</text></comment>
                                        </consequence>                                        
                                        <seq_changes>
                                                <variant id="1.3" type="AA">
                                                        <ref_seq source="uniprot" accession="O43918"/>
                                                         <name  scheme="HGVS">p.Met1Leu</name>                                                        
                                                        <consequence 
term="altering initiation codon in HSR domain"/>
                                                </variant>
                                        </seq_changes>
                                </variant>
                        </seq_changes>
                        <creation_date>2006-10-09</creation_date>
                        <modification_date>2006-10-09</modification_date>
                </variant>   
                <variant id="2" type="DNA">
                        <gene source="HGNC" accession="AIRE"/> 
                        <ref_seq accession="D0003"/>
                        <name  scheme="HGVS">g.8473C&gt;T</name>
                        <exon>6</exon>
                        <seq_changes>
                                <variant id="2.1" type="RNA">
                                        <ref_seq accession="C0003" />
                                        <name scheme="HGVS" >r.769c&lt;u</name>
                                        <seq_changes>
                                                <variant id="2.2" type="AA">
                                                        <ref_seq source="uniprot" accession="O43918"></ref_seq>
                                                        <name  scheme="HGVS">p.Arg257X</name>
                                                        <consequence 
term="premature stop codon in the HSR domain">
                                                                <comment><text>

out of frame translation; premature termination

</text></comment>
                                                        </consequence>
                                                </variant>
                                        </seq_changes>
                                        
                                </variant>
                        </seq_changes>
                        
                </variant>
                <db_xref source="pubmed" accession="16965330"/>                
        </individual>
</lsdb>

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VarioML LSDB-XML Extensibility:
Variant Report module

VarioML has been designed to be extensible to serve the spectrum of variant data exchange needs. We have included here one such extension: a Variant Report format to serve the need for data exchange in a variant-centric format. This also serves as an example of how to extend the VarioML core ontology for diverse use-cases.

VREPORT-XML

Variant Reporting makes use of a VREPORT-XML schema, extending the available VarioML terms to provide a simple adaption for making variant reports on population frequency levels.

Where LSDB-XML is individual-centric, for locus specific and clinical databases, VREPORT-XML is population-centric, using the Panel class, for variant reports on population frequency levels.

VREPORT extends the VarioML model for use with National and Ethnic Mutation Databases (NEMDBs).

VREPORT-XML format differs from the LSDB-XML format in two major ways:

• the main element is renamed vreport
• individual is replaced by panel

Extending VarioML with domain-specific Schema

The VREPORT-XML schema includes and extends the core VarioML schema:

datatypes xsd = "http://www.w3.org/2001/XMLSchema-datatypes"
default namespace vml = "http://gen2phen.org/varioml/2.0"

namespace local = ""


include "lsdb.rnc" { start |= notAllowed }

## Relax NGC schema for Variation report data transfer
## Contact: Juha.Muilu (juha.muilu@helsinki.fi)
start = vreport 


## Variant report
vreport = element vreport {
    VmlSubmission
    , LSDB.vreport.fields
    , VmlAnnotatable
    , Vmlforeign.nodes
}


LSDB.vreport.fields  &=
    ## Frequency reports of population groups
    panel+  
      

Examples of VREPORT-XML submissions

VREPORT XML Example 1

VREPORT replaces individual with panel, which specifies a population of individuals.

 <vreport 
    xmlns="http://gen2phen.org/varioml/2.0"
    xmlns:xlink="http://www.w3.org/1999/xlink"
    xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" 
    xsi:noNamespaceSchemaLocation="vreports.xsd"
    >    
    <source id="exdb">
        <name>Example database</name>
        <contact>
            <name>Mr. Example</name>  
        </contact> 
    </source> 


    <panel id="0001">
        
        <frequency type="carrier">
            <category term="exist"/>
        </frequency>
        <population term="Finland" type="region"/>
        
        <variant id="1002">
            <gene accession="ACLY"/>
            <ref_seq accession="n123445"/>
            <name scheme="HGVS">c.12345G>A</name> 
           
        </variant>
    </panel>
    
</vreport>

<vreport
  xmlns='http://gen2phen.org/varioml/2.0'
  xmlns:xlink='http://www.w3.org/1999/xlink'
  xmlns:xsi='http://www.w3.org/2001/XMLSchema-instance'
  xsi:noNamespaceSchemaLocation='vreports.xsd'>

   <source>
      <name>Findis database</name>
      <contact>
         <name>Juha Muilu</name>
      </contact>
      <comment><text>This release contains only mutations which have reference sequence</text></comment>
   </source>
   <panel>
       <phenotype accession="LCCS" 
term="Lethal congenital contracture syndrome" source='OIMIM' />
       <phenotype accession="LAAHD" 
term="Lethal arthrogryposis with anterior horn cell disease" source='OIMIM' />
       <population type="ethnic" term="Finnish"/>	
       <variant>
         <gene source="HGNC" accession="GLE1"/>
         <ref_seq accession="NM_001003722.1"/>
         <name scheme="HGVS">c.432-10A&gt;G</name>
            <consequence term="inframe_insertion; alternative_splicing" />
            <seq_changes>
                <variant type="AA">
                   <ref_seq accession="unknown"/>
                   <name>T144_E145insPFQ</name>
                </variant>
            </seq_changes>
            <modification_date>2009-06-03</modification_date>
            <db_xref source="pubmed" accession="18204449"/>
       </variant>
   </panel>		
   <panel>
       <phenotype accession="LCCS" term="Lethal congenital contracture syndrome" source='OIMIM' />
       <population type="ethnic" term="Finnish"/>	
       <variant>
         <gene source="HGNC" accession="GLE1"/>
         <ref_seq accession="NM_001003722.1"/>
         <name scheme="HGVS">c.1706G&gt;A</name>
            <seq_changes>
                <variant type="AA">
                   <ref_seq accession="unknown"/>
                   <name>R569H</name>
                </variant>
            </seq_changes>
            <modification_date>2009-06-03</modification_date>
            <db_xref source="pubmed" accession="18204449"/>
       </variant>
   </panel>		
</vreport>

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VREPORT NEMDB Example

This more complex example shows how VREPORT extends VarioML for use with National and Ethnic Mutation Databases (NEMDBs).

<?xml version='1.0' encoding='UTF-8'?> 
<vreport 
    xmlns="http://gen2phen.org/varioml/2.0"
    xmlns:xlink="http://www.w3.org/1999/xlink"
    xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" 
    xsi:noNamespaceSchemaLocation="vreports.xsd"
    > 
     
    <source > 
        <name>FINDbase-PGx</name> 
        <contact> 
            <name>George Patrinos</name> 
        </contact> 
    </source> 
    
    <panel> 
 
        <frequency samples="50" type="allele"> 
            <freq>0.06</freq> 
        </frequency> 
        
        <population type="group" term="Yorubans"/> 
        <population type="region" term="Nigeria"/> 
        <variant> 
            <gene accession="CYP3A5"/> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
            <db_xref source="dbsnp" accession="rs776746"/> 
            <comment term="name"><text>CYP3A5*3</text></comment> 
        </variant> 
        
    </panel> 
 

    <!-- 

    Note that frequency can also be associated with a set of alleles 
(the frequency of existence of both alleles at the same time)
 -->
    
    
    <panel> 
        <frequency samples="224" type="allele"> 
            <freq>0.763</freq> 
        </frequency> 
        <population type="group" term="El Salvadorans"/> 
        <population type="ethnic" term="Mestizo"> 
            <comment><text>Amerindian and European descent</text></comment> 
        </population> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
        </variant> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.1289T>G</name>                                    
        </variant> 
    </panel> 
 
 
    <!-- 
        Note that variant can also contain a variant specific frequency. 
Usage must be agreed upon on a case-by-case basis
 when setting up the data transfer protocol. 
    --> 
    
    
    <panel>      
        <population type="group" term="Yorubans"/> 
        <population type="region" term="Nigeria"/> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                
            <frequency samples="50" type="allele"> 
                <freq>0.06</freq> 
            </frequency> 
            
        </variant> 
    </panel> 
    
 
    <panel> 
        <frequency samples="66" type="allele"> 
            <freq>0.11</freq> 
        </frequency>            
        <population type="group" term="Baka Pygmies"/> 
        <population type="region" term="Central African Republic"/> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
        </variant> 
    </panel> 
    
    <panel> 
        <frequency samples="640" type="allele"> 
            <freq>0.145</freq> 
        </frequency> 
        <population type="group" term="South Africans"/> 
        <population type="region" term="Transkei area of Eastern and Western Cape"/> 
        <population type="language_family" term="Xhosa"/> 
        <population type="race" term="Black"/> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
        </variant> 
    </panel> 
 
    <panel xmlns="http://gen2phen.org/varioml/2.0" > 
        <frequency samples="196" type="allele"> 
            <freq>0.145</freq> 
        </frequency> 
        <population type="group" term="Malays"/> 
        <population type="ethnic" term="Singapore Malays mainly from the Malay Archipelago"/> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
        </variant> 
    </panel> 
 
    <panel> 
        <frequency samples="222" type="allele"> 
            <freq>0.64</freq> 
        </frequency> 
        <population type="group" term="Brazilians"/> 
        <population type="ethnic" term="'Pardo'"> 
            <comment><text>brown/intermediate</text></comment> 
        </population> 
        <population type="region" term="Rio de Janeiro"></population> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
        </variant> 
    </panel> 
 
    <panel > 
        <frequency samples="224" type="allele"> 
            <freq>0.763</freq> 
        </frequency> 
        <population type="group" term="El Salvadorans"/> 
        <population type="ethnic" term="Mestizo"> 
            <comment><text>Amerindian and European descent</text></comment> 
        </population> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
        </variant> 
    </panel> 
 
    <panel> 
        <frequency samples="176" type="allele"> 
            <freq>0.926</freq> 
        </frequency> 
        <population type="group" term="Yakuts"/> 
        <population type="region" term="Village of Cheriktei in the Sakha (Yakutia) Republic"> 
        </population> 
        <variant> 
            <ref_seq accession="NM_000777"/> 
            <name>g.6986A>G</name>                                    
        </variant> 
    </panel> 
</vreport>

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VarioML classes and properties cross-reference

VarioML introduces the following classes and properties:
See the VarioML schema for more details.

Schema Document Properties

Declared Namespaces

Global Declarations

Element: acknowledgement

Element: address

Element: aliases

       <variant> 
            <ref_seq source="genbank" accession="NG_001337.2"/>
            <name scheme="HGVS"> g.22048C>G</name>
            <aliases> 
                <variant> 
                    <ref_seq accession="NG_002335.2"/>
                    <name> g.1400G>C</name>                    
                </variant>
                <variant> 
                    <ref_seq accession="NG_007072.2"/>
                    <name> g.14034G>C</name>
                </variant>
                <variant> 
                    <ref_seq accession="NG_007088.1"/>
                    <name> g.28259G>C</name>
                </variant>                
            </aliases>
            
            <db_xref source="dbsnp" accession="rs13"/>
        </variant>

Element: call

Element: category

Element: chr

Element: comment

<comment> 
	<text> simple comment</text>
</comment>

<comment source="example_ontology" term="example term"> 
	<text> my defined comment</text>
</comment>

<comment> 
	<text> whatever</text>
  	<comment> 
            <text> my structured comment</text>
	</comment>
</comment>
      
<comment> 
	<text> whatever</text>
 	<comment> 
		<text> my complex structured comment</text>
		<evidence_code term="something"/>
		<db_xref accession="xyz"/>
	</comment>
</comment> 

<phenotype term="Autoimmune polyglandular syndrome type 1"> 
 <comment term="symptom"> <text> Hypoparathyroidism</text></comment>
 <comment term="symptom"> <text> Addison's disease</text></comment>
 <comment term="symptom"> <text> Mucocutaneous candidiasis</text></comment>
 <comment term="symptom"> <text> Malabsorption</text></comment>
 <comment term="symptom"> <text> Chronic active hepatitis</text></comment>
</phenotype>

Element: consent

Element: consequence

<consequence sourcels="SO" accession="1000071" term="mutation affecting splicing"/>

Element: contact

Element: counts

Element: created

Element: creation_date

Element: cultivar

Element: db_xref

<db_xref source="pubmed" accession="16965330"/>

Element: dob

Element: email

Element: embargo_end_date

Element: end

Element: evidence_code

<evidence_code term="inferred"/> 

<evidence_code term="confirmed" source="vario"/>

dbSNP validation should be used for mutations
Not validated (accession=0), Multiple reporting (1), With frequency
(2),Both frequency (3), Submitter validation (4)

Element: exon

<exon> 01</exon>   

Element: fax

Element: freq

Element: frequency

<frequency samples="1000"> 
	<population type="nationality" term="Finnish"/>
	<freq> 0.2</freq>
</frequency> 

<frequency> <freq> 0.1</freq></frequency>
					
<frequency samples="1000"> 
	<cases> 11</cases>
</frequency>

<frequency> 
	<population type="region" term="Sweden"/>
	<category term="exist"/>
</frequency>      
			  
<frequency samples="1111"> 
	<population type="ethnic" term="Caucasian"/>
	<freq> 0.12</freq>
	<evidence_code source="sampling_ontology" accession="abcd" term="random"/>
</frequency>

Element: frequency_value

Element: gender

	
  <gender code="9"> 
      <description term="XX-male"/>
  </gender>

Element: gene

<gene source="HGNC" accession="BRACA2"/>

<gene source="HGNC" accession="BRACA2"> 
	<db_xref accession="600185" uri="http://www.ncbi.nlm.nih.gov/omim/600185" source="OMIM"/>
	<db_xref accession="BRACA2" source="HGNC" uri="http://www.genenames.org/data/hgnc_data.php?hgnc_id=1101"/>
</gene>

Element: genetic_origin

<genetic_origin term="inherited"> 
   <source term="paternal"/>
   <evidence_code term="inferred"/>                                
</genetic_origin>

Element: genotype

Element: grant_number

Element: group_type

Element: individual

   <individual> 
        <gender code="2"/>
        <phenotype term="Osteogenesis Imperfecta"> 
        </phenotype>
        <variant type="cDNA"> 
            <gene source="HGNC" accession="COL1A1"/>
            <ref_seq accession="NG_007400.1"/>
            <name scheme="HGVS"> c.579delT</name>
            <genetic_origin term="paternal"> 
                <evidence_code term="inferred"/>            
            </genetic_origin>
            <sharing_policy type="openAccess"> 
                <embargo_end_date> 2002-12-12</embargo_end_date>
                <use_permission accession="CC0" uri="http://creativecommons.org/publicdomain/zero/1.0/" term="Creative commons"/>
            </sharing_policy>
                        
            <comment> 
                <text> Variant inherited from affected father</text>
            </comment>
                      
        </variant>
    </individual>

Element: inheritance_pattern

Element: location

<location> 
  <ref_seq source="embl" accession="ABC1023345"/>
  <start> 111111</start>
  <end> 111112</end>
</location>

<location> 
  <ref_seq accession="build36"/>
  <chr> 21</chr>
  <start> 111111</start>
  <end> 111112</end>
</location>

Element: lsdb

<lsdb xsi:noNamespaceSchemaLocation="lsdb.xsd"> 
    <created> 2000-01-12T12:13:14Z</created>
    <source id="AIREbase" version="1.2" uri="http://www.uta.fi/imt/bioinfo/AIREbase/"> 
        <name> DatabaseXYZ</name>
        <url> http://www.uta.fi/imt/bioinfo/AIREbase/</url>
        <contact> 
            <name> Matti Meik?l?inen</name>
            <address> Institute for Molecular Medicine</address>
        </contact>
        <acknowledgement> 
            <name> European Union</name>
            <grant_number accession="23230001"/>
        </acknowledgement>
    </source>

    <individual id="xyz"> 
        <gender code="2"/>
        <variant> 
            <ref_seq accession="xyz"/>
            <name scheme="HGVS"> c.1343G>T</name>
        </variant>
    </individual>

    <individual id="abce"> 
        <gender code="2"/>
        <variant> 
            <ref_seq accession="xyz"/>
            <name scheme="HGVS"> c.1343G>C</name>
        </variant>
    </individual>
    
</lsdb>

Element: modification_date

<modification_date> 2001</modification_date>
<modification_date> 2001-09</modification_date>
<modification_date> 2001-09-10</modification_date>

Element: observations

<genetic_origin term="paternal"> 
  <evidence_code term="inferred"/>            
</genetic_origin>
            
<phenotype term="Osteogenesis Imperfecta"> 
  <evidence_code term="assessed by clinician"/>
  <protocol_id source="protocoldb_xyz" accession="XYZ0001"/>
</phenotype>

Element: organism

Element: original_id

Element: panel

    <panel> 
        <frequency samples="224" type="allele"> 
            <freq> 0.763</freq>
        </frequency>
        <population type="group" term="El Salvadorans"/>
        <population type="ethnic" term="Mestizo"> 
            <comment> <text> Amerindian and European descent</text></comment>
        </population>
        <variant> 
            <ref_seq accession="NM_000777"/>
            <name> g.6986A>G</name>                                    
        </variant>
        <variant> 
            <ref_seq accession="NM_000777"/>
            <name> g.1289T>G</name>                                    
        </variant>
    </panel>
  

    <panel>       
        <population type="group" term="Yorubans"/>
        <population type="region" term="Nigeria"/>
        <variant> 
            <ref_seq accession="NM_000777"/>
            <name> g.6986A>G</name>                                                
            <frequency samples="50" type="allele">  
                <freq> 0.06</freq>
            </frequency>
        </variant>
    </panel>

Element: phenotype

<phenotype term="Autoimmune polyglandular syndrome type 1"/>

<phenotype term="Autoimmune polyglandular syndrome type 1" accession="240300" source="OMIM"> 
    <evidence_code term="confirmed" source="vario"/>
    <protocol_id accession="observation_method_xyz" source="protocol_database"/>
	<db_xref accession="12345" source="pubmed"/>
    <comment term="symptom"> <text> Hypoparathyroidism</text></comment>
    <comment term="symptom"> <text> Addison's disease</text></comment>
    <comment term="symptom"> <text> Mucocutaneous candidiasis</text></comment>
    <comment term="symptom"> <text> Malabsorption</text></comment>
    <comment term="symptom"> <text> Chronic active hepatitis</text></comment>
</phenotype>

Element: phone

Element: population

<population type="ethnic" term="Caucasian"/>                    

<population type="ethnic" term="Caucasian">  
	<evidence_code source="example_ontology_term" accession="abcd" term="ethnicity of mother"/>
</population>

<population type="ethnic" term="Asian">  
	<evidence_code source="example_ontology_term" accession="abcd" term="ethnicity of father"/>
</population>

<population type="region" term="Ahvenanmaa" source="ISO 3166" accession="ISO 3166-2:AX">  
	<evidence_code term="place of birth"/>
</population>

Element: protocol_id

Element: ref_seq

<ref_seq source="genbank" accession="NG_007088.1"/>

Element: reference

Element: relationship

Element: restriction_site