Found the gene that causes cystic fibrosis
"Knowing science can enrich your life. Basically, science is a foundation for genuine common sense."
Molecular geneticists try to understand the structure and function of genes. Lap-Chee Tsui is particularly interested in the gene for cystic fibrosis and other genes on human chromosome number 7. Chromosomes are threadlike strands found in the nuclei of animal and plant cells that carry hereditary information about the organism in DNA molecules.
After Tsui found the CF gene in 1989, he had to figure out exactly what that gene did. Over the years, he and his team have discovered that the DNA sequence with the mutation was part of the instructions for making a special protein called CFTR (Cystic Fibrosis Transmembrane conductance Regulator), a part of the cell membrane in certain special epithelial (surface) cells that generate mucus. These special cells might line the airways of the nose and lungs or the stomach wall.
The CFTR protein regulates a channel through the cell wall for chloride ions, which, through a process called osmosis, adjusts the “wateriness” of fluids secreted by the cell. Proteins are made of long chains of amino acids. The CFTR protein has 1,480 amino acids. Kids with cystic fibrosis are missing one single amino acid in their CFTR. Because of this, their mucus ends up being too thick and all sorts of things become difficult for them. Thanks to Tsui’s research, scientists have a much better idea of how the disease works. We can now easily predict when a couple will produce a child with cystic fibrosis. With increased understanding, scientists may also be able to devise improved treatments for children born with the disease.
Why do one in 25 Caucasians carry the mutation for CF? Tsui thinks that people who carry it may also have linked beneficial mutations that might, for instance, give them more resistance to diarrhea-like diseases. It’s not uncommon in nature to find the “good” linked with the “bad.”
1. Human chromosome 7: The cystic fibrosis gene sits on the long arm of chromosome 7. One out of every 25 people in the Caucasian population carries the genetic mutation for CF in this gene. Chromosome 7 has 150 million base pairs or units of DNA.
2. The cystic fibrosis gene: Using microbiological techniques, Tsui first localized the CF gene product to a region of the chromosome. The region has 230,000 DNA base pairs that spell out a series of 1,480 amino acids that curl up to make the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein. The little triangle shows the location of the three-base-pair deletion mutation that Tsui and his team discovered.
3. Model of CFTR protein in cell membrane: A normal gene makes CFTR that regulates the passage of chloride ions and hence the secretion of mucus in epithelial (surface) cells lining the gut, lungs and so on. One missing amino acid at this spot causes the majority of cases of CF. The remainder are caused by more than 1,200 other kinds of mutations of the CFTR gene, each accounting for a small percentage of cases.
ACTIVITYhas 1 activity for you to try in the Activities section.
The genes of a monkey and a human are almost identical, varying by only about 2 percent. How can such a small difference result in such different animals? Why do humans develop into humans and monkeys into monkeys? It has to do with the way an organism controls which genetic instructions are read from its DNA. This control system is called “the regulation of gene expression” and is still very poorly understood. Tsui likens the situation with monkeys and humans to two orchestras, each having exactly the same instruments and the same music to play: they can sound entirely different if they have different conductors. The greatest mystery to Tsui is identifying and characterizing the “conductor” in the human genetic system.
Frank DeFord, Alex: The Life of a Child, Rutledge Hill Press, 1997.
David M. Orenstein, Cystic Fibrosis: A Guide for Patient and Family, Lippincott Williams & Wilkins, third edition, 2003.
Cystic Fibrosis information from the Mayo Clinic.
Links and more information on Medline Plus.