China's "core" read the deafness genetic code
January 25, 2019 Source: Health News Network Author: magic world,
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Collect a drop of neonatal heel blood, and extract the nucleic acid sample extracted from it into a piece of slide measuring 7.5 cm long and 2.5 cm wide and put it into a matching instrument of ordinary printer size to know the subject. Whether to carry the hereditary deafness gene. The Chinese original world's first hereditary deafness genetic detection chip system has benefited more than 3.2 million newborns in China and has gone abroad. Its research and development team, Tsinghua University, the People's Liberation Army General Hospital and Boao Bio-Group, won the second prize of the 2018 National Technology Invention Award.
Early diagnosis and prevention of cockroaches gave birth to China's "core"
Hearing impairment is the second largest birth defect disease in China. There are 20.54 million people with hearing disabilities in China, including more than 800,000 children aged 0-6, and 30,000 new children are added each year. Studies have shown that about 60% of severe deafness is caused by genetic factors; 4% to 5% of normal deafness gene carrying rate is the main cause of adult scorpion and the next generation of deaf children. Traditional deaf screening and diagnostic techniques are cumbersome, low-throughput, and labor intensive.
Cheng Jing, an academician of the Genetic Deafness Gene Diagnostic Chip System Project and an academician of the Chinese Academy of Engineering, said: "To solve these problems, we must first find the genes of the Chinese people, and then solve the existing detection chips and equipment problems."
Since 2003, the PLA's General Hospital of the People's Liberation Army has collected 7,630 clinical cases of deafness and 2,8 cases of normal individuals, and conducted molecular etiological studies on high-risk populations of hereditary deafness. GJB2, SLC26A4, 12SrRNA and GJB3 were identified as Chinese population. The main hereditary deafness gene and its 9 mutation hotspots. These genes and loci are the "targets" that need to be targeted for detection.
With the "target", it is necessary to upgrade the "gun". The core of the "gun" is the chip. The project team invented high-precision multiplex allele-specific amplification and general-purpose chip technology, skillfully introducing artificial mismatched base technology at appropriate positions of amplification primers, magnetic bead separation and enrichment of single-stranded DNA technology, and accurate surface tension Control hybridization technology, integrate these four technologies, and design a high-precision, high-sensitivity, high-throughput mutation site detection chip.
Cheng Jing said: "The low sensitivity of the chip requires the collection of a large number of samples, which is traumatic and difficult to achieve for newborns. Magnetic beads separation and enrichment of single-stranded DNA technology has improved the detection sensitivity of the chip by 25 times. Thus, a drop of foot With blood, a little oral saliva, hair follicles are enough."
Around the chip core technology, the project also invented a fully automatic liquid workstation, chip scanner, chip hybrid instrument, chip washer, chip spotter, five supporting instruments, covering sample preparation, hybridization reaction, post-hybridization cleaning and scanning, etc. process. "This complete set of instruments and solutions is suitable for large-scale screening applications, and can detect deafness gene sites of congenital deafness, drug-induced deafness, and delayed deafness." Cheng Jing revealed that the detection ability of hereditary deafness gene chip is from The first generation of 4 genes and 9 sites will be extended to the second generation of 4 genes and 15 sites. In the future, chip products covering more genes and sites will be developed to provide more powerful diagnosis for rare diseases. tool.
3.2 million newborn screening for deafness genes
Screening for high-risk populations of newborns and deafness is beneficial to avoid drug-induced deafness and reduce the birth rate of late-onset deafness and offspring. Cheng Jing said that women of childbearing age should pay special attention to drug-induced deafness screening because the drug-induced deafness gene can be protected by the maternal inheritance, tracking maternal members and issuing medication guidelines. In addition, the detection of congenital deafness early implantation of the cochlear implant helps restore hearing and does not miss the critical period of language development.
In 2009, Boao Bio-produced hereditary deafness gene detection chip system was put into the market, and it was promoted and applied in the fields of marriage and childbirth guidance, prenatal screening, screening for neonatal and high-risk groups, and diagnosis of deafness. In April 2012, Beijing carried out genetic screening for neonatal hereditary deafness and became the first city in the world to achieve genetic screening for neonatal deafness. A year later, the Beijing Municipal Health and Family Planning Commission commissioned a health economics expert to evaluate the implementation of the Beijing Deafness Gene Project screening. “The results are exciting.†Cheng Jing said, “The cost-benefit ratio of screening is 1:7.27, which means that early screening can save about 7 times the loss caused by treatment after onset.â€
Since then, more than 20 provinces (autonomous regions and municipalities) such as Chengdu, Zhengzhou, Fuzhou, Taiyuan, Nantong, Dongguan, Jinan, and Xinjiang have successively implemented genetic screening for neonatal hereditary deafness and incorporated them into the government's popular projects. By the end of 2018, more than 3.2 million newborns had been screened for genetic deafness in the country, and the total mutation rate was 4.4%. Among them, there were more than 8,400 drug-induced gene carriers, directly avoiding subjects and family members. About 80,000 people were paralyzed by improper use of drugs.
Chinese technology is going abroad
Hereditary deafness gene diagnostic chip technology has received international attention.
In 2014, the second largest medical center in the United States and the University of Miami Medical School initiated a request to the project research team. Cheng Jing said that at the request of the University of Miami, the team developed the first genetic detection chip and supporting reagents for detecting Caucasian hereditary deafness using the self-developed microfluidic array chip technology platform. The chip can simultaneously detect and Caucasians have 9 loci associated with 5 genes associated with hereditary deafness. At present, the chip has entered the clinical trial stage, and the results have been highly recognized by international counterparts.
Professor Liu Xuezhong, a member of the American Academy of Surgeons and director of the Hereditary Deafness Center of the University of Miami Medical School, pointed out that at the 10th International Conference on Cochlear Implants and Related Sciences in Asia and the Chinese Conference on Genetics in 2015, "Based on Molecules The results of the etiology study developed deafness chips and applied them to large-scale deafness screening, providing a new way for early diagnosis and prevention of caries."
At the beginning of 2016, the hereditary deafness gene diagnostic chip product was granted a medical device license issued by the Ministry of Health and Welfare of Taiwan and entered the Taiwan market. In July 2017, the genetic deafness gene diagnostic kit was awarded the medical device registration certificate issued by the Food and Drug Administration of the Ministry of Public Health of Thailand.
Cheng Jing said that in order to further improve efficiency, the team has successfully developed an all-in-one system based on advanced microfluidic chip technology, which can automatically complete hybridization, cleaning and scanning operations in 15 minutes to 20 minutes. Hybridization and cleaning time is better than before. Shortened by about 4 times. Preliminary experiments have shown that the entire inspection process can be completed in two hours.
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