Separating Chromosomes Key to Applied Genetics
When scientists finished mapping the human genome in 2003, researchers promised the discovery would produce amazing applications in medical and anthropological research. But so far, those advances have yet to materialize.
One of the major constraints is that current technology ignores that the human cells are diploid they have a copies of each chromosome.
"What you get is a grab bag of four million [genetic] variants," said Jay Shendure, associate professor of genome sciences at the University of Washington. "What you don't get is which chromosome it is on."
To get a more accurate picture of human genetics, Shendure and other biomedical researchers are working to tease out which genes sit on which chromosome. Their work was named a top 10 emerging technology by the editors at MIT Technology Review.
There are different approaches to separating chromosomes out.
Shendure splits up the genomes in to smaller chunks of 40,000 base pairs (of about 3 billion total in the human genome) and then taking a subsample of those smaller pieces to find which genes appear on which chromosome. Stephen Quake, a biophysicist at Stanford University, instead sorted out the individual chromosomes before sequencing the genome by trapping individual cells as they're ready to divide and extracting out individual chromosomes.
"Conceptually both [approaches] are the same," Shendure told InnovationNewsDaily, "we're both subsampling the genome many times."
All of the current approaches in this burgeoning field have significant limitations. Cloning chunks of the genome is labor intensive and it doesn't yield full chromosomes, Shendure said, while Quake's approach is also technically challenging to get the chromosomes out of the cell.
Although there could be various applications in health care, the most likely place where this detailed information will be used clinically is during pregnancy. Shendure said doctors could potentially screen for Mendelian disorders diseases caused by one single gene mutation during pregnancy. "It's going to be something we couldn't do before."
Matching genes to chromosomes will also open up the possibility of single gene therapies and provide new insight into population genetics that could help researchers understand ancient migrations.
Shendure said that there will likely be more than one approach likely a combination of techniques that will allow the whole field to scale.
"Someone is going to figure out how to do this," Shendure said. "Ten years is a pretty conservative estimate."