The genetic chain reaction approaches us | Science

The genetic chain reaction approaches us | Science

The star technique of genetics laboratories (CRISPR) has been functioning in recent years with normality and discretion. Except for two exceptions of serious ethical implications: the birth of two girls genetically edited in China (with the intention of protecting them from AIDS) and the elimination of a whole population of mosquitoes with a variant of the technique called genetic impulse (gene drive, also called "supermendelian inheritance" or, more spectacularly, "genetic chain reaction"). This method has just been applied for the first time to a mammal (the mouse), as you can read in Subject. The gene that spreads in chain is not designed to exterminate the population of mice, as in the case of the mosquito, but only to change their color. But work is a proof of principle. We now know that the genetic drive works in mammals, and only the imagination is the limit. Surely science fiction novelists will take notice soon.

But let's go back to the present, because the most immediate application of the genetic impulse in mice has the feet well attached to the ground. In fact, it is a question more arid than sexy, but it can be very useful for biomedical research, generating mice with complex combinations of human genes that serve as models of arthritis and cancer. It's about the following. If the reader remembers his Mendelian genetics from school, he will immediately calculate that by crossing two individuals heterozygous for a mutation (that is, they carry the mutation in dad's chromosome, but not in mom's, or vice versa), a quarter of the progeny will be homozygous (with the mutation in both chromosomes). These homozygous mice are, in general, the only ones that are useful for modeling human diseases, and obtaining a quarter in each crossing is more than enough for that. But this, of course, only serves for monogenic, or "Mendelian" diseases, which are due to the alteration of a single gene.

The thing gets complicated immediately when working with more genes. For example, if one wants a homozygous mouse for three genes, it has to generate 146 offspring to have a sensible probability (90%) of obtaining it. With a dozen genes, conventional breeding is unfeasible in practice. And arthritis, cardiovascular risk and most types of cancer do not depend on a single gene, or three, but dozens. This is where the chain reaction can make a key difference. If the genes you want to homozygous are modified with the appropriate sequences (related to CRISPR), they are transmitted to the progeny more frequently than Mendel gives them, and the numbers are suddenly manageable.

The amazing properties of CRISPR, in this and other cases, are due to the ability of this system to generate, in the exact point of the genome that you want, cuts in the DNA (technically they are double band cuts, which break at the same time the two chains of the DNA double helix). In the case of genetic impulse, these cuts immediately trigger a natural mechanism called homologous recombination: the chromosome damaged by the cut invades the homologous chromosome, which is intact, and simply copies its sequence. Even before crossing with anyone, the heterozygous mouse becomes homozygous in the cells that will produce the ovules (the germ line). The genetic impulse is the nature placed at our service.

For the moment, the rest is science fiction.

THE SCIENCE OF THE WEEK It is a space in which Javier Sampedro analyzes scientific news.Subscribe to the newsletter of Matter and you will receive it every Saturday in your email, along with a selection of our best news of the week.


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