Chromosome high-throughput sequencing analysis

Chromosome high-throughput sequencing technology can detect microdeletions and microduplications as small as 10kb by adjusting the sequencing depth, breaking the throughput limit in disease research and having high resolution, high sensitivity and high accuracy. advantages. High-throughput sequencing technology has low requirements for specimens. At the same time, maternal cell contamination can be eliminated by drawing maternal blood for comparative analysis. While performing conventional karyotype analysis, seed materials can be reserved and the specimens can be re-tested using high-throughput sequencing technology. Thereby improving the detection success rate.

Genetic testing is usually divided into chromosome-level and gene-level testing. Let me emphasize again that clinical chorionic villus sampling, amniotic fluid or cord blood puncture actually refer to means of obtaining fetal samples rather than detection methods. After obtaining fetal samples, corresponding testing methods will be selected based on different clinical indications, such as chromosome culture karyotype analysis, chromosome copy number testing, genetic testing, etc. At present, the most commonly used detection methods at the clinical chromosome level are karyotype analysis and chromosome copy number (CNV) detection, while there are many most commonly used detection methods at the gene level, such as high-throughput sequencing, Sanger sequencing, and MLPA (multiple ligation-dependent probes). amplification), quantitative PCR, etc.

How to find a suitable detection method? There are many testing methods at the genetic level, and they are all complementary to each other. It does not mean that the whole exome is the most complete. Each single gene disease has its own most suitable testing method. For example: The current preferred testing method for Duchenne muscular dystrophy (DMD) is MLPA rather than whole-exome testing. Because more than 70% of children with the disease are caused by exon deletion of the DMD gene. Therefore, before testing, doctors may need to fully communicate with testing laboratories and/or testing institutions to provide patients and their families with the most suitable testing method, not the "most expensive" or "most complete" one.

Current status of prenatal genetic testing in China Prenatal genetic testing is currently almost only carried out in large domestic hospitals. There are roughly three common clinical situations that require prenatal genetic diagnosis: 1. There is a history of related single-gene inheritance in the family, such as parents who are sick or have given birth to affected children, and the pathogenic variant site has been identified. In order to prevent the fetus from suffering from the disease again, 2. Abnormality found in pre-pregnancy screening: no genetic history, but some screening was done during or before pregnancy Checks, such as carrier screening for couples, deafness gene screening, or fragile Short limbs need to be ruled out for FGFR3 gene mutations (few hospitals carry out this genetic test).

How to interpret genetic testing reports? Due to the complexity of genetic testing and the large regional differences in genetic testing and consultation levels in the country, it is not easy to accurately interpret the corresponding genetic testing reports. But for the majority of pregnant women, there is the simplest way to read the report. That is, under the premise that the disease-causing gene locus has been determined, we only need to see whether the locus in the amniotic fluid test report is the same as that of the patient at home. It is enough to be the same as normal people: if it carries one, two or more pathogenic sites like the patients at home, it means that the fetus is still a patient; if it carries non-pathogenic sites like normal people, it means that the fetus is still a patient. point, that means the fetus is basically normal. But this is the most basic way to look at the results. The actual situation may be much more complicated, so I still want everyone to remember one sentence: "For genetic variation interpretation and genetic counseling, it is recommended to go to a regular prenatal diagnosis institution to find a professional geneticist." Consult a doctor."