Incomplete Penetrance An example of a genetic factor causing disease resistance is incomplete penetrance. Incomplete penetrance is the result of a genetic
mutation not fully manifesting as the associated trait or disease. In the combined case of sickle cell anemia and malaria, individuals with one normal
allele and one sickle cell allele, (heterozygous HbAS), are largely healthy due to incomplete penetrance. They do not experience the effects of having sickle cell anemia, (due to the incomplete nature of the mutation), and gain resistance to malaria. This is due to the altered shape of their red blood cells due to the partial sickle cell trait, which impedes the
Plasmodium parasite, giving the individual resistance to the associated infection and disease caused by the parasite. Similarly,
Toll-like receptors (TLRs), which are naturally occurring proteins, are critical in recognizing pathogen-associated molecules, (including microbial and viral threats), and triggering immune responses. Notably, variations or specific alleles in these genes can strengthen the body’s ability to combat infections, showing how genetic traits can further contribute to innate immunity and pathogen resistance.
Hemoglobinopathies Hemoglobinopathies are a class of monogenic disorders that impact the major
red blood cell protein hemoglobin. Hemoglobinopathies interfere either with hemoglobin production or change hemoglobin’s protein structure, respectively splitting them into the two categories of
thalassemias and structural variants. These disorders exist due to alpha- or beta-globin gene mutations, Levels of
type-1 interferon (IFN-I) cytokines involved in the stimulation of immune response and
tumor necrosis factors (TNF) proteins involved in an inflammatory immune response can be altered by the introduction of testosterone hormones by individuals undergoing masculinizing gender-affirming treatment. Interferons are synthesized by
plasmacytoid dendritic cells (pDCs) which have toll-like receptors (TLR-7) that modulate their activity, so with the introduction of testosterone downregulating TLR-7 production in pDCs, interferons are consequently downregulated. Testosterone reduces the impact of IFN-I responses in pDCs while increasing the intensity of pro-inflammatory pathways involving TNF. == See also ==