Single Cell Genetic Map Construction via Whole Genome Sequencing
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Solution Overview
Problem
Current methods for constructing genetic maps in humans are limited by the difficulty in obtaining sufficient progeny for statistical analysis, particularly for mammals, and are unable to effectively amplify unknown genes and fragments, resulting in a one-sided and deficient genetic map.
Innovation Solution
A method and device for constructing a genetic map using whole genome sequencing of a single cell, aligning the data to a reference sequence, deducing genotypes through maximum parsimony of recombination, and dividing chromosomes into linkage regions to determine recombination rates, which can be used to construct a comprehensive genetic map, especially for mammals like humans.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional methods of constructing genetic map are used based on statistical analysis of randomly allocating homologous recombination event, then the method can be applied to species with sufficient progeny, but it cannot be well applied to humans and mammals due to lack of sufficient progeny for statistical analysis
Solution Approach 1:
Instead of analyzing multiple progeny to infer parental haplotypes (traditional approach), the patent inverts the approach by directly sequencing single sperm cells to obtain paternal haplotypes directly, eliminating the need for multiple progeny samples
Solution Approach 2:
The patent uses whole genome amplification to copy the genomic DNA from a single sperm cell, creating sufficient DNA material for sequencing and analysis, thereby enabling genetic map construction from a single cell
2Measurement precision
If only known genes are amplified for analysis using traditional methods, then the analysis can be performed with available primers, but unknown genes and fragments cannot be analyzed, resulting in a one-sided and deficient genetic map
Solution Approach 1:
The patent employs whole genome sequencing technology that can simultaneously sequence all genomic regions including known genes, unknown genes, and non-coding regions, eliminating the need for gene-specific primers and providing comprehensive genetic information in a single analysis
Data Source
AI summary
Provided are the method and device for genetic map construction and the method and device for haplotype determination of a single cell. Wherein the method for genetic map construction includes: whole genome sequencing for at least a single cell from a same species, aligning the sequencing data to reference sequences respectively to determine genotypes of SNP sites, determining male parent a/female parent b typing results of SNP genotypes of a single cell based on the genotypes of SNP sites, dividing the chromosome of the species into linkage regions based on the male parent a/female parent b typing results of SNP genotypes, determining the variation ratio of a/b between two linkage regions to obtain recombination rate between every two continuous linkage regions, determining recombination map of a single cell according to the recombination rate, wherein the boundary site of a and b is the recombination site, determining the recombination rate of each recombination rate based on the recombination map to construct a genetic map of the species.