New prenatal whole genome sequencing or revolutionizes prenatal care

New prenatal whole genome sequencing or revolutionizes prenatal care

Release date: 2016-08-31



In 1969, Led Zeppelin (a British rock band) released their first music album; in the same year, California doctors found that they sometimes detected the Y chromosome in the blood cells of pregnant women. This means that pregnant women have boys, and these cells come from the fetus in the pregnant woman's belly. The presence of embryonic cells circulating in maternal blood immediately inspires scientists to analyze the genetic lesions of the fetus.

However, no one thought that it would take 50 years to achieve this goal, and most of the scientists who participated in it gave up.

In fact, embryonic cells are very rare in the blood of pregnant women. These cells are not only difficult to find, but there may be only 10 in an ounce (about 28.3 grams) of blood, sometimes not at all.

In the face of this difficulty, some people did not give up. Art Beaudet (pictured above) said that such a blood test is possible and his team has mastered the preliminary evidence.

As a well-known doctor professor in the Department of Molecular and Human Genetics at Baylor College of Medicine in the United States, Bedert admits: "Everyone has always been highly suspicious of someone who can implement this technology. It is a very difficult and long road."

According to his prediction, as many as 12 biotech companies have registered to develop embryonic cell-based prenatal testing technology, but they have failed.

This test, which Bedert pursues, can revolutionize prenatal care because an embryonic cell perfectly carries all the information about the fetal genome.

If scientists can reliably extract such cells from their mother's blood, it means they have an unprecedented treasure trove of data – and a way to detect whether a fetus has a serious genetic disease.

If this test is widely adopted, every DNA letter of every baby that will be born will eventually be revealed.

At present, many pregnant women use another method: detecting embryonic DNA molecules floating in the blood of pregnant women. This type of NIPT non-vasive prenatal testing can be said to be a commercial success because it allows for simple and easy screening of Down's syndrome, a serious genetic disease caused by a redundant chromosome.

But Bedt believes that such tests actually “increased” the number of undetected genetic lesions because they not only failed to detect minor genetic problems, but also the number of people seeking traditional amniocentesis testing. decreased.

In traditional amniocentesis, the doctor inserts a long needle into the abdomen of the pregnant woman and extracts the cells for analysis. The result has been the gold standard for prenatal testing.

Bedd said that he has been motivated by "continuous family births with severely disabled babies." His tests will be able to detect gene deletions and doublings within the chromosome, including those de novo mutations (meaning that these mutations are newborn in the fetus, not inherited from the parents). Like NIPT, this cell-based test can also detect larger chromosomal errors, such as trisomies, or additional copies of chromosomes.

Once such a process is established, Beddett will work to discover smaller denovo mutations, including those in the context of approximately 500 genes, which can occur in pregnant women up to 1:200. Together, he said, these genetic errors occur five times more often than Down's syndrome and can lead to a range of rare diseases, including a subset of autism, as well as Prader-Willi, which causes mental retardation and uncontrollable hunger and obesity. Syndrome.

Currently, Bedt is working with two biotech companies, ArcediBiotech and RareCyte, which provide the technology to find and extract one cell from millions of cells in a blood sample. Headquartered in Seattle, RareCyte uses scanners that are only microwave-sized. They provide the technology to find and extract a cell from millions of cells in a blood sample. A placental trophoblast can be found in the blood of pregnant women (trophoblasts). ), its DNA composition is the same as that of the fetus.

Once the cell is found, RareCyte can suck it out with tiny tubes. Bedd said his data shows that the results of DNA analysis and other tests performed in such single cells are similar, but he also acknowledges that the technology is not automated enough and the results of each test are not consistent enough. Therefore, it is not currently put into routine use.

Diana Bianchi believes that Bedt's method is too difficult. She is a geneticist and neonatologist at the Tufts Medical Center and has many years of experience in studying embryonic cells. More importantly, the way DNA is read from a cell can cause errors because it must be replicated many times. Bi Anqi said: "It sounds tempting, just like the ex-boyfriend said to you, 'Can we be together again?', but I don't think anything in this relationship has really changed. I have been I feel that we need a huge technological or biological change to induce more embryonic cells to enter the mother's blood circulation."

Contrary to the development of new testing methods, Bi Anqi put the bet on the further improvement of the existing prenatal blood test. These tests search the blood of pregnant women for DNA fragments that leave the cell, which have been widely used and proven to be effective. Although 90% of the DNA belongs to the mother, 5-10% are from the placenta or embryo and can be sequenced by rapid-fire sequencing machines. Such tests can find large genetic lesions, such as an extra chromosome, but because the mother and baby's DNA are mixed together, the researchers can't find small but still serious mistakes.

"Art (Bedert) is not a fool," Ronald Wapner said. He is a maternal and child expert and clinical geneticist at Columbia University Medical Center and has conducted similar embryonic cell searches a few years ago. He has spent a lot of time on this project.

"Art has been looking for embryonic cells in the blood of pregnant women. This is his long march. He has spent a lot of time on it. Why should you continue on this long march? Because it will change everything."

Ultimately, extracting a cell will be a routine way to obtain a complete gene sequence, even making it possible to detect changes in a single letter of DNA.

Wapner said that with just one cell, "you can sequence the entire embryo's genome and find a point mutation [that is, a subtle change in a single base (note: the base is the smallest unit of DNA)] This is impossible to achieve now."

Bedt hopes that Baylor College of Medicine can expand the existing testing scale in the next few months, and strive to complete 10 research-based tests per week.

If it goes well, the next step is to market the embryonic cell test method, which is priced at about $3,000, although this price needs to fall below $1,000 to compete with existing extracellular DNA tests.

At present, pregnant women are still advised to confirm the results of non-invasive tests through invasive prenatal testing.

However, the idea that parents can know in advance that their child's entire genetic makeup - every health risk or even his / her hair color - is still controversial.

Bedert said: "People will argue whether this is fair to the fetus."

He said that Baylor College of Medicine did not focus on sequencing all genomes, but instead focused on identifying serious health problems.

"It's important to discover genetic mutations that cause very serious diseases. This is the center of all efforts."

Source: DeepTech Deep Technology

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