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Is DNA from Dad or Mom?

We all know that a healthy person has a pair of genetic sequences and one of the copies is from dad and the other from mom. Previous technology enables scientists to perform testing on the whole genetic sequences, yet it can’t determine whether a particular genetic sequence comes from an individual’s father or mother. Now, a newly developed technique successfully takes on this longstanding challenge in DNA sequencing. The new findings done by researchers from Ludwig Cancer Research have been published in Nature Biotechnology on November 3rd.

Human has a long history of evolution and the DNA sequences from our ancestors have been disrupted due to genetic recombination of numerous generations’ reproduction. Those intact, undisrupted DNA sequences inherited from father or mother are called Haplotype. Under the direction of Professor Bing Ren, Ludwig Cancer Research successfully developed a new technique called “Haploseq”. Combining molecular biology and bioinformatics methods, Haploseq could enable researchers to quickly which genetic variants occur together on the same stretch of chromosome and hence, came from the same parent.

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Working mechanism of HaploSeq:(a) Proximity ligation experiment: cross-linked DNA chains become fragments and ligated, then they are taken out from cells to test sequences; (b) Using sequencing results to construct Haplotype. *Image source: Siddarth Selvaraj et al. Nature Biotechnology. 2013.

The researchers firstly used proximity ligation-based sequencing method to sequence genomes. Cross-linked DNA chains were cut by restriction enzyme and then ligated into sequences. These sequences contain insert sequences of different lengths, ranging from 500 bp to chromosome span. By analyzing short sequences, scientist could obtain many small Haplotype domains while long sequences can ligate these haplotype domains and distinguish Haplotype. When the sequencing reaches a certain extent, researchers will be able to integrate all the discontinuous Haplotype domains into a Haplotype—the genotype inherited from father or mother.  Bing Ren said:” This technique will enable clinicians to better assess a person’s individual risk for disease. It is potentially transformative for personalized medicine.”

Bing Ren noted that since the technique is based on traditional sequencing methods, it will be easily adopted by clinical staffs. The most immediate application of this technique will be the assessment of an individual’s risk for disease. For example, people at risk for a disease like cancer usually have more than one DNA mutation. HaploSeq can enable clinicians to determine whether the two mutations are on the same chromosome or on different ones, which could help in risk assessment—for instance, risk might be reduced if two mutations are on the same chromosome, since the “good” chromosome can often compensate.

Moreover, the method, with further honing, has the potential to refine current cumbersome process of determining whether there is a genetic match between an organ donor and recipient.  A large number of genes contribute to compatibility between organ donor and recipient, however, there is a lot of genetic variability in these genes. This new technique will help determine whether DNA differences between organ donor and recipient are likely to be a good match. “The application calls for further research. We need to establish a DNA database to pair recipients and donors more accurately and expediently.”

In addition, the new approach can help researchers analyze human migration and determine ancestry from their DNA sequences.  Ren says: “In general, you can compare your genetic sequence to your neighbor’s and ask if you have any recent common ancestors. Similarly, we could study each individual and how they relate to other individuals. As we acquire data from more individuals, we could more accurately determine their relationships.” Such new findings will also benefit an ongoing international project to evaluate worldwide human genetic variation—the HapMap project.

Source:EurekAlert!

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