METHODS FOR ASSESSING GENOMIC INSTABILITIES
The invention generally relates to methods for assessing a fetal abnormality.
1 . A method of assessing a fetal abnormality, the method comprising:
analyzing a nucleic acid from a sample comprising fetal nucleic acid;
identifying one or more genomically unstable loci in the nucleic acid;
assigning a weighted value to each genomically unstable locus; and
assessing a fetal abnormality based on the weighted values.
2 . The method according to claim 1 , wherein the weighed value is based on severity of the genomically unstable locus.
3 . The method according to claim 1 , wherein the weighted value is based on a type of genomic instability.
4 . The method according to claim 3 , wherein the type of genomic instability is selected from the group consisting of additions, deletions, substitutions, translocations, alterations, amplifications, and single nucleotide polymorphisms.
5 . The method according to claim 1 , wherein the weighted value is based on a location of the genomically unstable locus.
6 . The method according to claim 5 , wherein the location is selected from the group consisting of: location on a chromosome, proximity to telomeres, and proximity to known or suspected locations of genomic instabilities found in certain fetal abnormalities.
7 . The method according to claim 1 , wherein the weighted value is based on a number of nucleotides within each genomically unstable locus.
8 . The method according to claim 1 , wherein analyzing comprises sequencing the nucleic acid.
9 . The method according to claim 8 , wherein sequencing is sequencing-by-synthesis.
10 . The method according to claim 8 , wherein identifying comprises comparing the sequenced nucleic acid to a reference nucleic acid to thereby identify the genomically unstable loci.
11 . The method according to claim 1 , wherein prior to the assigning step, the method further comprises categorizing the genomically unstable loci.
12 . The method according to claim 11 , further comprising deriving a weighted sum for each category.
13 . The method according to claim 11 , wherein categorizing is based on a type of genomic instability.
14 . The method according to claim 11 , wherein categorizing is based on a location of the genomically unstable locus.
15 . The method according to claim 1 , wherein the sample is a maternal sample.
16 . The method according to claim 15 , wherein the maternal sample is blood or amniotic fluid.
17 . The method according to claim 1 , wherein the sample is a fetal sample.