Approved Research

Population-scale phenotypes of haploinsufficiency of genes typically inherited in a recessive fashion

Lay summary

Aim. The aim of this project is to test whether genetic variants occurring in genes that we and others have linked to severe childhood disease can predispose adults to disease. Rationale. There are several examples of genes that are mutated in severe childhood diseases with recessive inheritance, where a common variant in that same gene predisposes to adult disease. Every infant inherits two copies of every autosomal gene, one from mum and one from dad.

Many genetic diseases occur when an infant inherits broken copies of a gene from both parents. For these recessive disorders, mum and dad usually do not display disease from one broken copy of the gene. In many cases, having one copy of a broken gene can lead to new traits, like having resistance to malaria or HIV. However, the effect of being a carrier for one broken gene can manifest in more subtle and nuanced ways. A carrier might behave differently or process nutrients differently than noncarriers. Studying the relationships between phenotypes of carriers and noncarriers can lead to new clinical tests to identify risk individuals and drug targets for therapy. Most importantly, by exploring the differences between carriers of these broken genes and noncarriers will be a great leap forward in solving the mystery of how changes to genes lead to changes of physical traits.