In 2018, Chao et al. flagged the BMP antagonist SOSTDC1 as a population-specific one of these genes, since reducing its expression is associated with lower age of onset exclusively in Venezuelan Huntington’s disease patients. For 10 points each:
[10h] Name these genes that cause heterogeneity in disease manifestation. Screens named after these genes introduce secondary mutations to find loci that alter a primary mutation’s phenotype.
ANSWER: genetic modifiers [or modifier genes; prompt on epistasis or epistatic genes by asking “what type of epistatic gene?”] (Low SOSTDC1 expression is associated with a three-year reduction in average age of HD onset in Venezuelan patients.)
[10m] Because it regulates hepcidin production in the liver, BMP2 modifies this other disease. In females, menstrual blood loss reduces the penetrance of this disease, which is most often caused by the C282Y mutation in HFE.
ANSWER: primary hemochromatosis [accept hereditary hemochromatosis, genetic hemochromatosis, or classical hemochromatosis; prompt on iron overload]
[10e] The specific variants that modify Huntington’s and hemochromatosis are both this type of mutation, which is visualized in a GWAS (“G-woss”). These point mutations with a three-letter acronym must occur in at least one percent of the population.
ANSWER: SNPs (“snips”) [or single-nucleotide polymorphisms]
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