Curating Family Information

The top section of the curation interface shows the publication currently being curated.

The "Curate Family Information" page is split into relevant sections based on the type of evidence. The first three sections are in a similar format to the same sections in the "Curate Group Information" page. All required fields (marked with a star) must be filled in before the curated record for a family can be saved. The required fields are:

• Family Label is a free-text identifier assigned by the curator. It should be used to uniquely identify a family described in a publication. If possible, use the identifiers that the authors use to label the family in the paper.

• Family -- Disease(s) & Phenotype(s) requires information in at least one of the two categories: Disease(s) in common (usually select “Copy disease term from Gene-Disease Record”) or Phenotype(s) in common (HPO terms or free text).

• Family -- Segregation requires information on the number of affected individuals with the relevant genotype.

In the "Family -- Demographics" section, use the drop-down menus to enter any information about family demographics that were provided in the publication.

In the "Family -- Methods" section, you can enter details about prior testing within the family and the genotyping method(s) used to establish that members of the family carry a variant in the gene of interest.

The "Family -- Segregation" section is composed of two subsections. The "Tested Individuals" section allows you to enter the number of affected/unaffected individuals with/without the genotype under consideration. In addition, if information on segregations within the family is available, you can enter this number here. An estimated LOD score will be calculated if the required number of segregations for the mode of inheritance is met and will be shown in the following "LOD Score" section.

The "LOD Score" section allows you to enter the LOD score if one was included in the publication. Selecting "Yes" in the "Published LOD score?" dropdown menu will enable you to enter the numerical value in the "Published Calculated LOD score" field.

If there is either a published LOD score or an estimated LOD score based on reported segregations, and if this score should be included in the final aggregate calculation, select "Yes" in the following dropdown menu.

A box is provided to add free text to "Explain reasoning" behind a decision to include or exclude a published LOD score. An additional free text box allows "Additional Segregation Information" to be entered.

Depending on your selection, the estimated or published LOD score will appear in the corresponding section of the Evidence Matrix and Scored Evidence summary.

The "Family -- Variant(s) Segregating with Proband" section enables you to associate a proband and the segregating variant with this family.

The "Proband Label" field is a free-text field and should contain information that uniquely identifies the proband. If possible, use the label given in the publication; do not use a real name.

The disease ID(s) for the disease(s) associated with the Family is automatically shown and can be copied to the proband. Alternatively, a different disease term can be selected.

The options for checkboxes presented below the disease term differ depending on the mode of inheritance. The example below shows the option for dominant inheritance; if the proband is known to be hemizygous, check the provided box. For recessive inheritance, you will have the option to indicate the presence of one homozygous variant or two variants in trans (see below).

To associate the relevant variant(s) with the proband, click the "Add Variant" button. For further information on adding variant information, see the Adding Variant Information section.

If you are scoring segregation without an associated proband in the GCI, note that once you have entered the information on a proband, if you do not enter a proband name and save, it will only associate the LOD score to segregation section only, and will not automatically associate a proband with the family. This may be accurate as some older literature on linkage analysis may have only talked about a family without a proband or identified variant. This would be categorized on the final gene curation record as “segregation without a proband.” However, if you do intend to associate a proband, please enter in a “proband name” when prompted, or if you forget, you can go to the GCI gene curation main page, choose the appropriate PMID, pick the family, and click the “add individual” button. See for example this RPE65 record.

The final "Family Additional Information" section allows you to enter any additional relevant information about the family. In particular, if the same family is described in any other publications, this could be noted here.