CRISPR technology application to quickly identify genetic variants

(Original title: Science: A new application of CRISPR technology to quickly identify genetic variants)

[China Pharmaceutical Network Technology News] It has been found that genetic variation is limited to research at low-resolution natural meiotic recombination rates. It is reported that a research team led by Leonid Kruglyak of UCLA has recently developed A new technology uses the genetic editing system CRISPR to quickly identify genetic variants.

The findings may significantly advance research efforts to map genes and determine their function. Related papers were published in the May 5th issue of Science.


Finding differences in DNA sequences that are the basis of trait variation is a central goal of modern genetics research. The main tools currently associated with genotypes and phenotypes are linkage and association studies. Although linkage and association studies have mapped tens of thousands of genomic regions that contribute to phenotypic variation, narrowing these regions to potential pathogenic genes and mutations can be challenging.

Traditionally, it has been found that genetic variation has been limited to research at low-resolution naturally occurring meiotic recombination rates. During meiotic recombination, cells undergo two divisions to produce germ cells, and genetic material is “reshuffled”. Usually, because the meiotic recombination rate is too low to analyze the mapping region of a single gene, let alone the specific variation within the gene.


Mitotic reorganization affecting somatic cells allows us to understand gene function and variation in more detail, as it sometimes leads to the formation of recombinant chromosomes with a set of genes rather than two sets of genes. This can cause some genes to lose their function and provide some important insights that they play a key role. However, mitotic recombination is a rare event.

In this Science article, Kruglyak and co-authors point out that although mapping studies have revealed many trait loci for decades, identifying potential genes and mutations has lagged behind. They have developed a new type of CRISPR-assisted mapping that promises to eliminate this gap. Their approach leverages CRISPR to generate directed recombination events that densely cover areas of any size.

The researchers first generated a CRISPR-guided loss of heterozygous (LOH) event across a yeast chromosome arm, using the resulting yeast strain to map for trait variation. They then allowed a QTL compartment to be filled with recombination events to quickly identify a causal polymorphism responsible for manganese sensitivity in laboratory S. cerevisiae strains.

The researchers confirmed the causal role of this polymorphism by using CRISPR-assisted direct manipulation of resistance alleles into a sensitive yeast strain. Compared to previous strategies, the new method generates higher density recombination events that can easily target any region of the genome without the need for additional time-consuming generation of hybridization systems to increase recombination frequency.

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