Genes and transporters

The human genome has around 18,000 to 20,000 genes that code for proteins. I often wonder how much the field has learned about the function(s) of each of these genes. One thing about human genetics that has never ceased to amaze me is how naturally occurring spelling errors in the gene sequences in the population shed light on the normal functions of the genes. The value of something is appreciated only when it is lost. Many of the genes in the human genome were known to exist today only because scientists encountered humans in the past in whom such genes didn't exist, functionally speaking.

One class of genes that I find particularly interesting are the ones that encode transporters and ion channels. Millions of molecules are on a constant move in the human body, and often their movements are facilitated by transporters and channel proteins. They let molecules shuttle in and out of cells and cell organelles. Sometimes the cells merely act as passages through which molecules enter into or exist out of the human body to conduct their day-to-day businesses. Genetic mutations that partially or completely block such passages create traffic jams, leading to crowding of the passengers either inside or outside the body and send signals to scientists, setting the stage for new discoveries.

One channel protein that probably comes to everyone's mind with the mention of human genetics is cystic fibrosis gene CFTR. It encodes chloride channels in the cells lining the walls of the ducts that allow air to flow into the lungs, digestive enzymes to flow through the pancreas and sweat to be released from sweat glands. Loss of this channel blocks the movement of chloride and sodium and consequently, water, across the ductal epithelial cells, dehydrating and driving up the viscosity of the ductal contents.

One of the key pieces of the cystic fibrosis puzzle that helped scientists triangulate the genetic cause appeared during a hot summer in 1948 when a heat wave swept through the New York. Paul di Sant'Agnese, a pediatrician at the New York-Presbyterian Hospital, noticed that cystic fibrosis patients were disproportionately exhausted by the heat than other patients in the hospital. This observation led to the