Genetic disease high-throughput sequencing pathogenic mutation screening method based on core family

A screening method and a genetic disease technology, applied in the application and device fields of the above screening method, can solve the problems of being prone to errors and omissions, time-consuming and labor-intensive, etc.

Inactive Publication Date: 2021-02-19
SHANGHAI CHILDRENS HOSPITAL
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  • Claims
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Problems solved by technology

However, the manual method of core family analysis is very time-consu

Method used

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  • Genetic disease high-throughput sequencing pathogenic mutation screening method based on core family
  • Genetic disease high-throughput sequencing pathogenic mutation screening method based on core family
  • Genetic disease high-throughput sequencing pathogenic mutation screening method based on core family

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1 2

[0070] Example 1 Genotype Display Mode in Next Generation Sequencing

[0071] Genotype refers to the general term for the entire gene combination of an individual organism, reflecting the sum of the genetic material obtained by the organism from its parents. The genotype specifically used in genetics generally only represents the composition of alleles at individual or a few loci. For example, if the reference sequence of a certain SNP site is A, and the two alleles of the gene where the site is located in a person are A and T respectively, then the genotype of this person's site is A / T . The genotype contains a variety of mutation types, not only single base substitution, but also insertion, deletion, insertion / deletion, inversion and many other mutation types.

[0072] High-throughput sequencing technology, also known as next-generation sequencing technology, can determine the sequence of the target fragment, extract the sites different from the reference sequence, and rec...

Embodiment 2 2

[0114] Core Family Analysis in Example 2 Next Generation Sequencing

[0115] The core family analysis model for high-throughput sequencing of genetic disease-causing mutations is called the Trios model in English. The pathogenic mutations hidden under the disease phenotype confirm the origin of the disease. If high-throughput sequencing is performed on the proband, after the analysis finds a possible pathogenic mutation, and then the parents are verified by next-generation sequencing to determine the source of the pathogenic mutation in the proband, then this method of analysis is generally accepted. It is called proband analysis, not the core family analysis method mentioned in this article. More and more Trios family detection models have been used in domestic and foreign research literature on various genetic diseases in recent years. In 2014, an article was published on JAMA (Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, et al. Clinical exome seq...

Embodiment 3

[0119] The family combination type of embodiment 3 mutation

[0120] As mentioned above, the genotype of a certain mutation site in the proband has three situations, 0 / 0, 0 / 1, 1 / 1, and the parents also have the same three situations. A certain mutant genotype is combined, in theory, there are 27 kinds. They are: 0 / 00 / 00 / 0; 0 / 00 / 00 / 1; 0 / 00 / 01 / 1; 0 / 00 / 10 / 0; 0 / 00 / 10 / 1; 0 / 00 / 11 / 1; 0 / 01 / 10 / 0; 0 / 01 / 10 / 1; 0 / 01 / 11 / 1; 0 / 10 / 00 / 0; 0 / 10 / 00 / 1; 0 / 10 / 01 / 1; 0 / 10 / 10 / 0; 0 / 10 / 10 / 1; 0 / 10 / 11 / 1; 0 / 11 / 10 / 0; 0 / 11 / 10 / 1; 0 / 11 / 11 / 1; 10 / 00 / 0; 1 / 10 / 00 / 1; 1 / 10 / 01 / 1; 1 / 10 / 10 / 0; 1 / 10 / 10 / 1; 1 / 10 / 11 / 1; 1 / 11 / 10 / 0; 1 / 11 / 10 / 1; 1 / 11 / 11 / 1; plus special combinations belonging to other situations, a total of 28 kinds.

[0121] In the present invention, data analysis is performed on 10 families that have undergone whole-exon high-throughput sequencing experiments. The data for each combination is as follows:

[0122]

[0123]

[0124]

[0125] It can be seen from the above table that during the next-g...

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Abstract

The invention belongs to the field of gene mutation detection, and relates to a method for screening pathogenic mutations by using a core family analysis method based on genetic disease high-throughput sequencing data. The invention provides a genetic disease high-throughput sequencing pathogenic mutation screening method based on a core family, which comprises the following steps: obtaining a genome sample to be detected, the genome sample originating from filial generation and parents thereof; determining a DNA sequence of a genome sample to be detected by using a high-throughput method, andcomparing and annotating a sequencing result with a human reference genome to form an annotation file; analyzing and screening the annotation files by using a dichotomy, removing high-frequency mutation, and classifying the detected gene mutation; removing non-pathogenic mutations from the classification and annotation of the detected gene mutations. The method provided by the invention can become an effective tool for high-throughput sequencing analysis of genetic diseases, can quickly and accurately find out pathogenic sites, and realizes standardization, process and semi-automation of analysis.

Description

technical field [0001] Based on the high-throughput sequencing data of genetic diseases, the invention uses a core family analysis method to screen pathogenic mutations, and belongs to the field of gene mutation detection of genetic diseases in medicine. The present invention also provides the application and device of the above screening method. [0002] technical background [0003] At present, high-throughput sequencing represented by whole exome sequencing is the main method for the detection and diagnosis of human genetic diseases. High-throughput sequencing can discover a large number of mutations, determine the harmfulness of these mutations, and find out and confirm the pathogenic genes and pathogenic sites that cause patients, which are the main tasks of genetic disease genetic testing. [0004] Among the variants obtained by sequencing, some variants have a higher distribution frequency in the population. Higher distribution frequency means that if the variant is ...

Claims

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Application Information

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IPC IPC(8): C12Q1/6869C12Q1/6883G16B20/50G16B20/20G16B20/30
CPCC12Q1/6869C12Q1/6883C12Q2600/156G16B20/20G16B20/30G16B20/50C12Q2535/122
Inventor 杨永臣张颖宋小珍张泓李嫔黄如方
Owner SHANGHAI CHILDRENS HOSPITAL
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