Patent ID: 11879157
Assignee: NIPD GENETICS PUBLIC COMPANY LIMITED
Field: Biotechnology (Chemistry)
Classification: CPC C | IPC C

Claim 15:
16. A method of determining the status of a genetic condition or a fetal risk of inheriting a genetic condition, the method comprising:
(a) preparing a sequencing library from a sample comprising maternal and fetal DNA;
(b) hybridizing the sequencing library to a pool of single-stranded TArget Capture Sequences (TACS), wherein the pool of TACS comprises a plurality of TACS families directed to different genomic sequences of interest, wherein each TACS family comprises a plurality of member sequences, wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions with respect to a reference coordinate system for the genomic sequence of interest, and further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length, each member sequence having a 5′ end and a 3′ end;
(ii) each member sequence binds to the same genomic sequence of interest at least 50 base pairs away, on both the 5′ end and the 3′ end, from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements; and
(iii) the GC content of the pool of TACS is between 19% and 80%, as determined by calculating the GC content of each member within each family of TACS;

(c) isolating members of the sequencing library that bind to the pool of TACS to obtain an enriched library;
(d) amplifying and sequencing the enriched library;
(e) performing statistical analysis on the enriched library sequences to thereby determine maternal carrier status at the loci of interest associated with different genetic conditions;
(f) selecting, after step (e), the sample comprising maternal and fetal DNA carrying a variant allele associated with an inheritable genetic condition;
(g) obtaining a paternal DNA sample and performing steps (a)-(e) on the paternal DNA sample to determine paternal carrier status;
(h) selecting, after step (g), the paternal DNA sample carrying a variant allele associated with an inheritable genetic condition in common with the sample comprising maternal and fetal DNA carrying the variant allele associated with the inheritable genetic condition;
(i) determining fetal risk of inheriting a genetic condition based on maternal carrier status selected in step (f) and paternal carrier status selected in step (h).