Loss of Heterozygosity
In families with consanguinity, offspring have regions of loss of heterozygosity that result from shared ancestry. One or more genes in such regions can contribute to a clinical phenotype.
SimulConsult's Loss of Heterozygosity feature allows you to input a list of genes in such regions and get a differential diagnosis based on both the clinical phenotype and the genes being considered. The genes are arranged in order of pertinence, as determined by relevance to the differential diagnosis based on the clinical features. There are several advantages to this approach:
- The analysis is hypothesis-independent as to which findings are most important. It uses the same pertinence metric used in the Genome-Phenome Analyzer, based on the full clinical description, including multiple positive findings with onset information and multiple negative findings.
- The analysis is hypothesis-independent as to the number of genes involved, using the same pertinence metric used in the Genome-Phenome Analyzer. This ability to assess phenotypes resulting from more than one gene is particularly important for individuals with consanguinity, where loss of heterozygosity analysis is typically done.
To enable the Loss of Heterozygosity feature in the SimulConsult diagnostic decision support software, contact us. Then:
- If not in Advanced mode, click the checkbox in the upper right.
- Enter patient findings as usual, or use the File button to load a saved patient.
- Click the "Loss of Heteroz" button, paste in your gene list, and then click the Differential button.
- Click the Genotype tab to see the genes in your list that have a known biallelic human disease phenotype, arranged in order of pertinence. Note that for individuals with large loss of heterozygosity, it is not rare for more than one gene to contribute to the phenotype.
- Genes with no known biallelic human disease phenotype are accessible via the "Gene discovery" button.