SYSTEM AND METHOD FOR CLEANING NOISY GENETIC DATA FROM TARGET INDIVIDUALS USING GENETIC DATA FROM GENETICALLY RELATED INDIVIDUALS
A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available, are disclosed. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention incomplete genetic data is acquired from embryonic cells, fetal cells, or cell-free fetal DNA isolated from the mother's blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals.
1 . A method of determining the number of copies of a chromosome of interest or a segment of the chromosome in a fetal cell, the method comprising the steps:
obtaining an isolated fetal cell from the bloodstream of the mother of the fetus,
performing whole genome amplification on the isolated fetal cell, whereby amplified DNA is produced, and
obtaining quantitative DNA sequence information at a plurality of loci in the amplified DNA, wherein the DNA sequence information is sufficient to determine the number of copies of the chromosome or chromosome segment of interest in the fetal cell.
2 . The method according to claim 1 , wherein the whole genome amplification is performed by multiple strand displacement amplification reaction.
3 . The method according to claim 1 , wherein the whole genome amplification is performed by degenerate oligonucleotide primer amplification.
4 . The method of claim 1 , wherein a plurality of the loci have at least two alleles and the quantity of each allele in the amplified DNA is measured.
5 . The method of claim 4 , wherein the quantity of each allele is measured relative to the other allele at the same locus.
6 . The method of claim 4 , wherein the analysis comprises the step of hybridizing the amplified DNA to a nucleic acid array.
7 . The method of claim 6 , wherein the nucleic acid array is a bead array.
8 . The method of claim 1 , wherein the fetal cell is isolated by a fluorescence activated cell sorter.
9 . The method of claim 1 , wherein the fetal cell is isolated by an antibody.
10 . The method of claim 1 , comprising the step of comparing allelic data from the amplified DNA to parental allelic data from the loci of at least one biological parent of the fetus.
11 . The method of claim 10 , further comprising the step of obtaining a tissue sample from the biological parent and obtaining the parental allelic data from the sample.
12 . The method of claim 11 , wherein the parental allelic data is obtained by DNA sequencing.
13 . The method of claim 1 , wherein a plurality of fetal cells are isolated.
14 . The method of claim 13 , wherein no more than 10 fetal cells are isolated.