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Method and system for non-invasive detection of fetal chromosomal aneuploidy

A chromosome and Y chromosome technology, applied in the field of medical testing, can solve problems that affect the accuracy of the final result, do not consider the sequence preference between chromosomes, and construct an optimization model for sex chromosome data.

Active Publication Date: 2015-12-02
BOAO BIOLOGICAL CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, the above detection methods also have their own limitations: First, the GC bias of sequencing not only exists within the same chromosome, but also exists between different chromosomes, and the above method only considers the GC bias when solving GC bias. The sequencing bias caused by the difference in GC content of each sequence in each chromosome does not consider the bias of sequences between chromosomes
This causes a large deviation between the base percentage of the calculated chromosome and the real value, which affects the accuracy of the final result
Secondly, because the distribution of sex chromosomes in male fetuses is different from that of autosomes, and the above method does not separately construct an optimized model for sex chromosome data when performing aneuploidy analysis, the above method can only determine autosomal aneuploidy Abnormal, and can not make a good judgment for abnormal aneuploidy of sex chromosomes

Method used

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  • Method and system for non-invasive detection of fetal chromosomal aneuploidy
  • Method and system for non-invasive detection of fetal chromosomal aneuploidy
  • Method and system for non-invasive detection of fetal chromosomal aneuploidy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] Example 1: Building a reference database

[0095] 1. Select control blood samples

[0096] 500 peripheral blood samples from pregnant women whose gestational age was greater than or equal to 12 weeks and had no chromosomal abnormalities in karyotype analysis were selected to form the control blood samples in the reference database A (ReferenceA). Among them, the blood samples of 200 pregnant women with normal female fetuses constitute the control blood samples in the reference database B (ReferenceB).

[0097] 2. Accurate positioning of sequencing data

[0098] Compare the sequencing data with the human genome standard sequence hg19 to determine the exact position of the base sequence on the chromosome.

[0099] 3. Quality control of sequencing data

[0100] In order to ensure the quality of the sequencing results and avoid the interference of some repetitive sequences, low-quality sequences were eliminated, and the bases located in the tandem repeat and transposable...

Embodiment 2

[0107] Example 2: Construction of determination parameters and threshold ranges for X chromosome aneuploidy in male fetuses

[0108] 1. Calculate the Z value of X and Y chromosomes in male fetuses

[0109] Using ReferenceB as a reference database, calculate the Z values ​​of fetal X and Y chromosomes in the blood samples of pregnant women carrying normal male fetuses according to formula 1, that is, Z X and Z Y .

[0110] Z i =(x i -μ i ) / σ i (Formula 1)

[0111] i: chromosome number;

[0112] x i : Unique base percentage of chromosome i in the analysis data;

[0113] mu i : The average value of the Unique base percentage of chromosome i in the reference database;

[0114] b i : The standard error of the Unique base percentage of chromosome i in the reference database.

[0115] 2. Construct Z in male fetus X and Z Y relationship model between

[0116] According to the calculation formula of Z value, Z X and Z Y Both are related to the concentration of fetal D...

Embodiment 3

[0126] Embodiment 3: detection of the blood sample to be tested

[0127] 1. Whole genome sequencing of blood samples to be tested

[0128] Seven pregnant volunteers participated in this test, and the blood samples were numbered N1-N7. The results of karyotype analysis showed: 1 fetus with trisomy 21, 1 fetus with trisomy 13, 1 fetus with trisomy 18, and 1 male fetus with an extra Y chromosome , 1 pregnant with a female fetus lacking one X chromosome, 1 pregnant with a normal female fetus, and 1 pregnant with a normal male fetus.

[0129] The peripheral blood of each pregnant woman was drawn, centrifuged to obtain plasma, and then DNA was extracted from the plasma, using the IonProton of Life Company TM Sequencers perform large-scale, high-throughput sequencing. The above blood samples were collected by Guangzhou Women and Children's Medical Center.

[0130] 2. Count the percentage of Unique bases in chromosomes in the blood sample to be tested

[0131] By comparing and fi...

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Abstract

The invention belongs to the medical detection field, and discloses a method and a system for noninvasive detection of fetus chromosome aneuploid. The disclosed detection method and system also relate to a method and a system for elimination of sequencing GC preference in chromosomes and among chromosomes and a method and a system used for the relation model of the Z values of X and Y chromosomes in a normal male fetus. Through elimination of influences of sequencing GC preference in chromosomes and among chromosomes, the relation model of the Z values of X and Y chromosomes in a normal male fetus is built, and the determination threshold of difference between the theoretical value and the actual value of the Z value of the X chromosome is built. The accurate detection of fetus chromosome aneuploid, especially sex chromosome aneuploid is achieved.

Description

technical field [0001] The invention relates to the field of medical detection, in particular to a method for non-invasive detection of fetal chromosomal aneuploidy and a system for non-invasive detection of fetal chromosomal aneuploidy. Background technique [0002] Chromosomal aneuploidy is the most common chromosomal abnormality in fetuses, which can be divided into autosomal aneuploidy and sex chromosome aneuploidy according to different chromosome types. Autosomal aneuploidy mainly includes trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome), among which trisomy 21 is the most common , the incidence rate is about 1 / 800. Sex chromosome aneuploidy mainly includes Klinefelter syndrome (47, XXY), XYY syndrome, Turner syndrome (45, X) and superfemale syndrome (47, XXX), and the male incidence is about 1 / 500 , the female incidence rate is about 1 / 850. Prenatal diagnosis of fetal chromosomal aneuploidy is an important means to reduce bi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/68G06F19/20
CPCC12Q1/6881
Inventor 糜庆丰彭春芳刘海量何铮章芬陈样宜
Owner BOAO BIOLOGICAL CO LTD
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