Method for predicting mitochondrial DNA mutation threshold, fertility risk and egg taking number

Abstract

The invention discloses a method for predicting a mitochondrial DNA mutation threshold value, a fertility risk and an egg taking number. The method comprises the following steps: firstly, establishing a mitochondrial mutation incidence probability prediction model and estimating a mutation threshold value s, then establishing a fertility risk prediction model and predicting a fertility risk p of a mutation carrier, and then, establishing an oocyte extraction prediction model by utilizing binomial distribution, and calculating the PGT egg taking number of a mutation carrier. According to the method, the disease probability prediction model is used for estimating the threshold value of common mtDNA mutation, and the fertility risk and the PGT egg taking number of the mother are predicted. On the basis of the established fertility risk prediction model and an egg taking prediction model, the reproduction risk and the minimum PGT egg taking number required by reproduction of a healthy offspring can be calculated only by knowing the mitochondrial DNA mutation proportion of a mutation carrier, so that clinical doctors can carry out genetic management on families carrying mtDNA heteromutation and provide genetic counseling, and a standard guide of PGT is provided.

Description

technical field [0001] The invention relates to the technical field of mitochondrial disease prediction, in particular to methods for predicting mitochondrial DNA mutation threshold, fertility risk and number of eggs retrieved. Background technique [0002] Mitochondrial disease is one of the most common and serious genetic disorders with an estimated incidence of 1:4300. Mitochondrial DNA (mtDNA) mutations are a common cause of mitochondrial disease. Due to the lack of protective histones and imperfect DNA repair mechanisms, mtDNA mutations The rate is higher than that of nuclear DNA. Given that mitochondria can contain multiple copies of DNA, mtDNA mutations can affect all gene copies at the same time (called homoplasmy) or some copies (called heteroplasmy). In general, homoplasmic mutations are usually relatively It is mild and only affects one organ or tissue, while heteroplasmic mutations can affect multiple organ systems, leading to severe systemic mitochondrial geneti...

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Problems solved by technology

[0002] Mitochondrial disease is one of the most common and serious genetic disorders with an estimated incidence of 1:4300. Mitochondrial DNA (mtDNA) mutations are a common cause of mitochondrial disease. Due to the lack of protective histones and imperfect DNA repair mechanisms, mtDNA mutations The rate is higher than that of nuclear DNA. Given that mitochondria can contain multiple copies of DNA, mtDNA mutations can affect all gene copies at the same time (called homoplasmy) or some copies (called heteroplasmy). In general, homoplasmic mutations are usually relatively It is mild and only affects one organ or tissue, while heteroplasmic mutations can affect multiple organ systems, leading to severe systemic mitochondrial genetic diseases. At present, it is estimated that about 0.5% of the world's population carries pathogenic mtDNA mutations, which have been reported There are more than 300 pathogenic mtDNA mutations. However, there is no effective treatment for mitochondrial mutations. Since mtDNA mutations are only passed from mother to offspring, it is urgent to study methods to prevent maternal transmission of mitochondrial mutations.

[0003] A human oocyte contains about 100,000 mtDNA molecules. Due to the genetic bottleneck of mitochondria, only a small amount of mtDNA can be passed on during oogenesis, resulting in considerable differences in the mutation levels of offspring. Mutation levels, that is, mutations and normal The ratio of mtDNA is related to the occurrence of clinical symptoms and the severity of the disease. Only when the mutation level reaches a certain threshold, clinical symptoms will appear. The existence of genetic bottlenecks leads to females carrying mtDNA mutations, and their offspring have low mtDNA mutation levels. Determination makes the incidence of mitochondrial disease unpredictable, preimplantation genetic testing (PGT) can detect the level of mtDNA mutations in early embryos, and select the best embryos for transplantation to prevent the next generation of onset, PGT has been widely used to prevent mtDNA mutations However, the standard operating standard of PGT has not been established, and it is unclear how to select oocytes suitable for transplantation and how many oocytes need to be obtained before transplanting suitable embryos. Therefore, the present invention proposes a prediction Mitochondrial DNA mutation threshold, fertility risk and methods of egg retrieval to solve the problems existing in the prior art

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