Patent Document ID: 9547748
Application ID: 13641080
Patent Flag: 1

Claim One:
1. A method to determine a fetal chromosomal abnormality, which method comprises: a) obtaining sequence information of multiple polynucleotide fragments from a sample; b) assigning said fragments to chromosomes based on said sequence information by comparing the sequence of the fragments with a reference human genomic sequence; c) calculating coverage depth and GC content of a chromosome based on said sequence information, wherein the coverage depth of the chromosome is the ratio between the number of fragments that assigns to said chromosome and the number of Reference Unique Reads of said chromosome, and the GC content of the chromosome is the average GC content of all fragments that assign to said chromosome, wherein the Reference Unique Reads are fragments of a chromosome that have unique sequences each of which is unambiguously assigned to a single chromosomal location; d) calculating fitted coverage depth of said chromosome using said GC content of said chromosome and an established relationship between coverage depth and GC content of said chromosome, wherein the relationship is in the formula: 
 cr i,j =f ( GC i,j )+ε i,j , j= 1,2,. .. , 22 ,X,Y, wherein f(GC i,j ) represents the function for the relationship between coverage depth and the corresponding GC content of sample i, chromosome j, ε i,j represents the residual of sample i, chromosome j, and wherein the fitted coverage depth is calculated according to the formula: 
 c{circumflex over (r)} i,j =f ( GC i,j ), j= 1,2,. .. , 22 ,X,Y ; and e) comparing said fitted coverage depth to said coverage depth of said chromosome by a statistical hypothesis test to determine a fetal chromosomal abnormality selected from the group consisting of aneuploidy, polyploidy, monosomy, trisomy, and a sex chromosome abnormality.