Risk calculation for evaluation of fetal aneuploidy

Abstract

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

We claim: 
     
         1 . A computer-implemented process to calculate a risk of a fetal chromosome dosage abnormality in a maternal sample comprising:
 estimating the chromosome dosage for two or more chromosomes in the maternal sample;   determining a fetal nucleic acid proportion in the maternal sample;   calculating a value of likelihood that a fetal chromosome is aneuploid by comparing the chromosome dosage of a first chromosome to the chromosome dosage of a second chromosome in view of the fetal nucleic acid proportion in the maternal sample;   calculating a value of likelihood that the fetal chromosome is disomic by comparing the chromosome dosage of the first chromosome to the chromosome dosage of the second chromosome in view of the fetal nucleic acid proportion in the maternal sample;   calculating a risk of a fetal chromosome dosage abnormality for the fetal chromosome based on the value of the likelihood of the chromosome being aneuploid and the value of the likelihood of the chromosome being disomic.   
     
     
         2 . The process of  claim 1 , wherein the value of the likelihood is reported as an odds ratio. 
     
     
         3 . The process of  claim 1 , wherein the fetal nucleic acid proportion is determined using the dosage of two or more chromosomes in the maternal sample. 
     
     
         4 . The process of  claim 1 , wherein a total fetal nucleic acid proportion for the maternal sample is determined. 
     
     
         5 . The process of  claim 1 , wherein the aneuploidy is a result of one or no copies of a chromosome or part of a chromosome. 
     
     
         6 . The process of  claim 1 , wherein the aneuploidy is a result of three or more copies of a chromosome or part of a chromosome. 
     
     
         7 . The process of  claim 1 , wherein the maternal sample is a cell free maternal sample. 
     
     
         8 . The process of  claim 7 , wherein the cell free maternal sample is maternal plasma or serum. 
     
     
         9 . The process of  claim 1 , wherein the maternal sample comprises cells. 
     
     
         10 . The process of  claim 1 , further comprising the step of adjusting the value of the likelihood using extrinsic information. 
     
     
         11 . The process of  claim 10 , further comprising the step of adjusting the value of the likelihood using information related to maternal age. 
     
     
         12 . The process of  claim 10 , further comprising the step of adjusting the value of the likelihood using information related to gestational age. 
     
     
         13 . A computer-implemented process to calculate a risk of a fetal chromosomal anueploidy in a maternal sample comprising:
 estimating the chromosome dosage for two or more chromosomes in the maternal sample;   determining a fetal nucleic acid proportion in the maternal sample;   calculating a value of likelihood that a fetal chromosome is aneuploid by comparing the chromosome dosage of a first chromosome to the chromosome dosage of a second chromosome in view of the fetal nucleic acid proportion in the maternal sample;   calculating a value of the likelihood that the fetal chromosome is disomic by comparing the chromosome dosage of the first chromosome to the chromosome dosage of the second chromosome in view of the fetal nucleic acid proportion in the maternal sample;   calculating a risk of a fetal chromosome dosage abnormality for the fetal chromosome based on a value of the likelihood of the chromosome being aneuploid and a value of the likelihood of the chromosome being disomic.   
     
     
         14 . The process of  claim 13 , wherein the fetal nucleic acid proportion is determined using the dosage of two or more chromosomes in the maternal sample. 
     
     
         15 . The process of  claim 13 , wherein a total fetal nucleic acid proportion for the maternal sample is determined. 
     
     
         16 . The process of  claim 13 , wherein the aneuploidy is a result of one or no copies of a chromosome or part of a chromosome. 
     
     
         17 . The process of  claim 13 , wherein the aneuploidy is a result of three or more copies of a chromosome or part of a chromosome. 
     
     
         18 . The process of  claim 13 , wherein the maternal sample is a cell free maternal sample. 
     
     
         19 . The process of  claim 18 , wherein the cell free maternal sample is maternal plasma or serum. 
     
     
         20 . The process of  claim 13 , wherein the maternal sample comprises cells. 
     
     
         21 . The process of  claim 13 , further comprising the step of adjusting the value of the likelihood using extrinsic information. 
     
     
         22 . The process of  claim 21 , further comprising the step of adjusting the value of the likelihood using information related to maternal age. 
     
     
         23 . The process of  claim 21 , further comprising the step of adjusting the value of the likelihood using information related to gestational age.