The human genome sketch adds details to the X chromosome being decoded without dead ends.

This is a small step in gene sequencing technology, but it may be a big step in the development of human genetic engineering. Recently, researchers at the National Institutes of Health (NIH) Human Genome Research Institute (NHGRI) announced that they have finally obtained complete, gap-free, end-to-end sequence information on the human X chromosome.

The breakthrough findings, published in the journal Nature, suggest that it is possible to produce an exact base sequence of human chromosomes that produces a complete sequence of the human genome. “This achievement opens a new era in genomics research,” said Eric Green, M.D., director of NHGRI. “

The $3 billion Human Genome Project, launched in 1990, drew the first human genome work sketch in 2000 after a decade of effort. This is the most accurate and complete vertebrate genome sequence ever.

However, the “tight volume” carrying the human genetic code has not been deciphered 100 percent, there are still a large number of unknown gaps. Why have these gaps been delayed? What gene sequencing techniques are helping scientists obtain the complete sequence of the X chromosome this time? Can the remaining gene sequence blanks be filled in smoothly?

The human genome sketch adds details to the X chromosome being decoded without dead ends.

Sequencing the human genome is like a jigsaw puzzle.

If you have children at home, or you are a puzzle enthusiast, challenging more pieces and bigger puzzles must be your goal.

But have you thought that a group of scientists from different countries are also challenging a huge puzzle that could contain billions of pieces of debris? This huge jigsaw puzzle is actually what many institutions and scientists around the world have been working on for years, the human genome map.

DNA fragments store all information about the race, blood type, and processes of breeding, growth, and apoptosis of life. The life phenomena of living organisms, such as life, growth, decay, disease, old age and death, are related to DNA.

The human genome is very long and contains about 3 billion base pairs. By locating the exact location of these bases on the DNA chain, and then identifying and analyzing genes and their functions, humans will eventually conquer cancer, heart disease, Alzheimer’s disease and other persistent diseases.

It should be noted that the human genome is not a sequencing study of an individual. Humans have similar genes, whether you’re male or female, yellow-skinned or blue-eyed. However, everyone has their own “copy” of the genome, and each “copy” is slightly different.

Therefore, the concept of “reference genome” is often used in genomic research. The Reference Genome is a database of nucleic acid sequences assembled by scientists as a genome reference template for species.

The Genomic Reference Alliance (GRC) is responsible for updating reference genomes from time to time. But the reference genome is still incomplete, and there are many gaps in the DNA sequence waiting to be filled.

“Because the human genome is so long, no sequencing technology can read all the sequence information at once. As a result, scientists can only sequence genomes into small pieces and assemble them. Professor Wang Qianghu, head of the Department of Bioinintronics at Nanjing Medical University, said that to outsiders, the scientists were doing what was like a “jigsaw puzzle”.

In this puzzle, there are many repetitive sequences. Because sequencing technology can only complete movie segment reading, repeated sequences can cause many movie segments that look almost identical to appear. “It’s like the blue sky and the grasslands in the puzzle, where every little piece is blue or green, but there’s no clue how the pieces are stitched together.” ‘This has created a lot of gaps, ‘ Mr. Wang said.

The human genome sketch adds details to the X chromosome being decoded without dead ends.

The first thing to look at is the special X chromosome.

It is well known that human cells have a cell nucleation, the genetic material of the nucleuter on 23 pairs of chromosomes, one of which is a sex chromosome. If it’s female, it’s XX, but if it’s male, it’s XY. And half of everyone’s sex chromosomes come from fathers and half from mothers.

“There’s a reason scientists chose the X chromosome for replacement sequencing.” Wang Qianghu said that the X chromosome in 23 pairs of chromosomes of medium length, but also contains a lot of genetic information, once the X chromosome can be fully sequenced, will also provide a reference for the complete sequencing of other chromosomes in the future.

“That’s not to say the Y chromosome doesn’t matter.” Wang Qianghu said that the Y chromosome has 27 special encoding genes, X chromosome does not have, from this point of view, boys than girls 27 more from the father’s coded genes.

The case of the murder of a female student at Nanjing Medical University 28 years ago, which was solved in February this year, is to rely on Y-STR family identification technology, first through Y chromosome analysis to find the family, and then by collecting 11 male oral swabs in the suspect family and DAN ratio, to identify the criminal.

“The Y chromosome is male-only and can only come from the father’s genetics, somewhat similar to what the ancients called ‘one line’.” Wang Qianghu told reporters, is the grandfather passed to the father, the father passed to the son. Therefore, as long as a male Y chromosome is tested in a family, it is basically known what the Y chromosome of other men in the family looks like.

Women inherit two X chromosomes, one from the mother and one from the father. However, the two X chromosomes are not the same, and their DNA sequences contain many differences.

In this study, the researchers did not sequence the X chromosomes of normal human cells. Instead, a special female cell was chosen — two X chromosomes from the same source. This cell provides more DNA sequencing than male cells with only a single copy of the X chromosome. It also avoids the sequence differences encountered when analyzing the two X chromosomes of a typical female cell.

Nano-porous technology is the greatest contributor to X chromosome sequencing.

Compared to the sketch of the human genome obtained 20 years ago, this time the scientists sequenced the X chromosome in its entire right, with the greatest credit being the nano-hole sequencing technique.

“This is a third-generation sequencing technology.” According to Wang Qianghu, in 1996 Daniel Brandon of Harvard University, David Dimmer of the University of California and colleagues, in the Proceedings of the National Academy of Sciences, published an article for the first time in the United States, can use membrane channels to detect polynucleic acid sequences, become the origin of nano-hole sequencing technology.

The study used a special nano-hole sequencer that sequences DNA by detecting changes in the current as individual DNA molecules pass through small holes in the membrane (nano-holes).

“Nano-hole sequencing technology can obtain ‘ultra-long reads’ containing hundreds of thousands of base pairs, which can span the entire repeating area, bypassing some complex challenges.” Wang Qianghu told reporters that the first generation of gene sequencing technology can only read a few hundred base pairs at a time, in the past two decades, sequencing technology has made great progress, so that those once considered very difficult repeat sequence sequencing, become relatively easy.

“This is definitely a milestone.” By analyzing genetic information on the X chromosome, scientists may soon be able to overcome complex and difficult diseases, Wang said.

For example, there are well-known genes F8 (coagulation factor 8) and F9 (coagulation factor 9) on the X chromosome, and the lack of coagulation factors 8 and 9 can lead to haemophilia.

Because men have only one X chromosome, once problems occur, they cannot normally produce clotting factors 8 and 9. That’s why haemophilia usually occurs in men: women carry two X chromosomes, and if one chromosome has a problem and the other is normal, haemophilia usually doesn’t occur, but it’s passed on to the next generation.

Wang Qianghu believes that the new human genome sequence fills many gaps in the current human reference genome and opens up new areas for genomic research. But potential challenges remain, such as the fact that duplicate DNA fragments on chromosomes 1 and 9 are much longer than on chromosome X. Scientists plan to continue their efforts to close more unknown gaps.

At the same time, a number of genome projects for Chinese are also being implemented, Wang Qianghu said: “At present, the human reference genome is based on the European and American population as the original, but the European and American population and Chinese of the gene there are still nuances.” For example, professor Shen Hongbing of Nanjing Medical University, a member of the Chinese Academy of Engineering, found 19 susceptible genes associated with Chinese lung cancer through genome-wide association research, which can be used as a multigene genetic risk assessment index for lung cancer in Chinese groups to achieve forward-looking prevention. “