Prior studies have associated serum lipid levels, such as cholesterol, as a causal risk factor for heart disease. Both LDL and HDL cholesterol levels are highly heritable. Previous studies have discovered Mendelian variants for extreme levels of low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) cholesterol. We identified six Netherland families with extreme lipid levels where there was an apparent Mendelian inheritance and a lack of known Mendelian variants. Specifically, we looked at the following three dyslipidemias in these families: hypercholesterolemia (high LDL-C), hyper-alphalipoproteinemia (high HDL-C), and hypoalphalipoproteinemia (low HDL -C). We sequenced all the genes that are protein coding (i.e. exome) to identify a causal variant for each family. Assuming a model of complete penetrance, as well as a recessive or dominant model and mutations that would alter the protein sequence, we identified a small number of potential causal variants for each family. An analysis of a few of the dominant model families still remains to be done. Discovery of causal mutations for Mendelian dyslipidemias in one or more families may contribute to the future development of drugs.
"This summer experience opened my eyes to a variety of pathways. I never considered going to medical school before this summer and now I am open to the possibility. I feel so lucky to have had the opportunity to work at an institution where collaboration is highly valued and where the most cutting-edge medicinal research is taking place. SRPG was such a wonderful experience and I am so grateful to be a part of the Broad community."