Assay systems for determination of fetal copy number variation

Abstract

The present invention provides processes for determining accurate risk probabilities for chromosome dosage abnormalities. Specifically, the invention provides non-invasive evaluation of genomic variations through chromosome-selective sequencing and non-host fraction data analysis of maternal samples.

1 - 20 . (canceled) 
     
     
         21 . A computer-implemented process to calculate a risk of a fetal aneuploidy in a maternal serum or plasma sample from a pregnant female, the computer-implemented process comprising the following steps:
 1) estimating the chromosome dosage of a first fetal chromosome in the maternal sample;   2) estimating the chromosome dosage of one or more other fetal chromosomes in the maternal sample;   3) providing data on prior risk of aneuploidy for at least the first fetal chromosome based on extrinsic characteristics;   4) calculating a value of the likelihood that a first fetal chromosome is aneuploid by comparing the chromosome dosage of the first fetal chromosome to the chromosome dosage of the one or more other fetal chromosomes in view of the prior risk of aneuploidy;   5) calculating a value of the likelihood that the first fetal chromosome is disomic by comparing the chromosome dosage of the first fetal chromosome to the chromosome dosage of the one or more other fetal chromosomes in view of the prior risk of aneuploidy; and   6) calculating a risk of aneuploidy of the first fetal chromosome based on the calculated values of likelihood.   
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The process of  claim 21 , wherein the maternal sample comprises cells. 
     
     
         25 . The process of  claim 21 , wherein the data on prior risk of aneuploidy comprises information related to maternal age. 
     
     
         26 . The process of  claim 21 , wherein the data on prior risk of aneuploidy comprises information related to gestational age. 
     
     
         27 . The process of  claim 21 , wherein the chromosome dosage of the first chromosome is estimated interrogating at least twenty polymorphic loci on the first chromosome. 
     
     
         28 . The process of  claim 27 , wherein the chromosome dosage of the first chromosome is estimated by interrogating at least fifty polymorphic loci on the first chromosome. 
     
     
         29 . The process of  claim 21 , wherein the chromosome dosage of the first chromosome is estimated by interrogating at least five informative loci on the first chromosome. 
     
     
         30 . The process of  claim 29 , wherein the chromosome dosage of the first chromosome is estimated by interrogating at least twenty informative loci on the first chromosome. 
     
     
         31 . The process of  claim 21 , wherein the value of the probability of an aneuploidy is an odds ratio. 
     
     
         32 . The process of  claim 21 , wherein the value of the probability of an aneuploidy for the first fetal chromosome is based on a value of the likelihood of the chromosome being trisomic and a value of the likelihood of the chromosome being disomic. 
     
     
         33 . The process of  claim 21 , wherein the value of the probability of a chromosome dosage abnormality for the first fetal chromosome is based on a value of the likelihood of the chromosome being monosomic and a value of the likelihood of the chromosome being disomic. 
     
     
         34 . The process of  claim 21 , further comprising the following step:
 interrogating at least twenty polymorphic loci on a first fetal chromosome in the maternal sample and   interrogating at least twenty polymorphic on a second fetal chromosome in the maternal sample.   
     
     
         35 . The process of  claim 34 , further comprising the following step:
 determining fetal DNA contribution to the maternal sample.   
     
     
         36 . The process of  claim 35 , wherein the calculated values of likelihood are determined in view of the fetal DNA contribution to the maternal sample.