Detecting Genetic Abnormalities

Abstract

The present invention is directed to compositions and methods for detecting genetic abnormalities. The present invention encompasses methods and compositions for comparing alleles in a sample containing both maternal and fetal nucleic acids in order to identify genetic abnormalities.

1 . A method for determining whether a fetus has at least one genetic abnormality, said method comprising comparing at least three alleles, wherein said comparing identifies said at least one genetic abnormality. 
     
     
         2 . A method according to  claim 1 , wherein said comparing comprises detecting the number of molecules of each of said at least three alleles. 
     
     
         3 . A method according to  claim 1 , wherein said three alleles are alleles of a tandem single nucleotide polymorphism (SNP). 
     
     
         4 . A method according to  claim 2 , wherein said comparing comprises calculating a haplotype ratio. 
     
     
         5 . A method according to  claim 1 , wherein two of said at least three alleles are maternal alleles and one of said at least three alleles is a paternal allele that is not present in the maternal genome. 
     
     
         6 . A method according to  claim 5 , wherein said comparing comprises determining the number of molecules of each of said at least three alleles in said sample, and wherein if the number of molecules of said two maternal alleles is equal, said fetus has at least one genetic abnormality. 
     
     
         7 . A method according to  claim 5 , wherein said comparing comprises determining the number of molecules present in said sample for each of said at least three alleles, and wherein if the number of molecules of the three alleles is in the relationship of peak, x and peak+2x, the fetus has at least one genetic abnormality. 
     
     
         8 . A method according to  claim 5 , wherein said comparing comprises determining the number of molecules present in said sample for each of said at least three alleles, and wherein if the number of molecules of the three alleles is in the relationship of peak, x and peak+x, the fetus does not have a genetic abnormality. 
     
     
         9 . A method according to  claim 1 , wherein one of said at least three alleles is a paternally-inherited fetal allele. 
     
     
         10 . A method according to  claim 9 , wherein said comparing comprises calculating an allelic ratio, and wherein said paternally-inherited fetal allele serves as an internal standard for said allelic ratio. 
     
     
         11 . A method according to  claim 1 , wherein said at least three alleles comprise a member selected from:
 a deletion, an insertion, a variant sequence, methylation, and any combination thereof.