Mendelian inheritance
Creative Minds: Looking for Common Threads in Rare Diseases
Posted on by Dr. Francis Collins
Valerie Arboleda
Credit: UCLA/Margaret Sison Photography
Four years ago, Valerie Arboleda accomplished something most young medical geneticists rarely do. She helped discover a rare congenital disease now known as KAT6A syndrome [1]. From the original 10 cases to the more than 100 diagnosed today, KAT6A kids share a single altered gene that causes neuro-developmental delays, most prominently in learning to walk and talk, plus a spectrum of possible abnormalities involving the head, face, heart, and immune system.
Now, Arboleda wants to accomplish something even more groundbreaking. With a 2017 NIH Director’s Early Independence Award, she will develop ways to mine Big Data—the voluminous amounts of DNA sequence and other biological information now stored in public databases—to unearth new clues into the biology of rare disorders like KAT6A syndrome. If successful, Arboleda’s work could bring greater precision to the diagnosis and potentially treatment of Mendelian disorders, as well as provide greater clarity into the specific challenges that might lie ahead for an affected child.
Gene Drive Research Takes Aim at Malaria
Posted on by Dr. Francis Collins
Malaria has afflicted humans for millennia. Even today, the mosquito-borne, parasitic disease claims more than a half-million lives annually [1]. Now, in a study that has raised both hope and concern, researchers have taken aim at this ancient scourge by using one of modern science’s most powerful new technologies—the CRISPR/Cas9 gene-editing tool—to turn mosquitoes from dangerous malaria vectors into allies against infection [2].
The secret behind this new strategy is the “gene drive,” which involves engineering an organism’s genome in a way that intentionally spreads, or drives, a trait through its population much faster than is possible by normal Mendelian inheritance. The concept of gene drive has been around since the late 1960s [3]; but until the recent arrival of highly precise gene editing tools like CRISPR/Cas9, the approach was largely theoretical. In the new work, researchers inserted into a precise location in the mosquito chromosome, a recombinant DNA segment designed to block transmission of malaria parasites. Importantly, this segment also contained a gene drive designed to ensure the trait was inherited with extreme efficiency. And efficient it was! When the gene-drive engineered mosquitoes were mated with normal mosquitoes in the lab, they passed on the malaria-blocking trait to 99.5 percent of their offspring (as opposed to 50 percent for Mendelian inheritance).
