Genetic Data Reconstruction for Accurate Chromosome Copy Number
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current genetic data measurement techniques for pre-implantation genetic diagnosis (PGD) and prenatal diagnosis are unreliable, costly, and prone to errors such as allele drop-out (ADO), especially when analyzing single cells or small DNA samples, which can lead to incorrect genetic screening results and ethical dilemmas.
Innovation Solution
A system that uses secondary genetic data from related individuals, such as parents, siblings, or other embryos, to reconstruct and clean noisy genetic data from embryos or fetuses, improving the accuracy of chromosome copy number determination and disease-linked gene identification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If genetic data is measured from single cells or small DNA samples, then the cost and complexity of the procedure is reduced, but the measurement precision and reliability deteriorate due to allele drop-out and other errors
Solution Approach 1:
The patent introduces parental genetic data as an intermediary element to mediate between the noisy single-cell measurements and the true genetic state. By using parental genotypes as reference information, the system can distinguish true alleles from measurement errors, thereby improving measurement precision without requiring more expensive or complex direct measurement methods
Solution Approach 2:
The patent creates a virtual copy of the genetic information by inferring embryonic genotypes from parental data. This copying approach allows the system to obtain reliable genetic information indirectly through computational inference rather than direct physical measurement, resolving the contradiction between measurement reliability and cost
2Loss of time
If genetic data is measured from single cells or small DNA samples, then the procedure becomes faster and simpler, but the reliability of genetic screening deteriorates
Solution Approach 1:
The patent implements a feedback mechanism where parental genetic data is used to validate and correct single-cell measurements. The system continuously compares measured alleles against expected parental inheritance patterns, identifying and correcting errors such as allele drop-out, thereby maintaining high reliability despite using rapid single-cell measurement methods
Solution Approach 2:
Parental genetic data serves as an intermediary reference that bridges the gap between rapid single-cell measurements and reliable genetic screening. This intermediary information allows the system to achieve both speed and reliability by using computational inference to compensate for measurement limitations
3Ease of operation
If traditional genetic screening methods are used, then the procedure is straightforward, but the accuracy of aneuploidy detection and disease-linked gene identification deteriorates
Solution Approach 1:
The patent merges traditional single-cell genetic measurement with parental genotype analysis into a unified screening system. By combining these two data sources computationally, the system maintains the operational simplicity of direct measurement while achieving high accuracy through integrated analysis of multiple genetic references
Solution Approach 2:
The patent creates a multi-functional system that simultaneously performs aneuploidy detection, disease-linked gene identification, and genotype validation using a single integrated approach. This universal system handles multiple diagnostic functions without requiring separate complex procedures, maintaining ease of operation while improving accuracy
Data Source
AI summary
Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.