Methods for disease detection

• US 7,811,757 B2
• Filed: 09/07/2006
• Issued: 10/12/2010
• Est. Priority Date: 09/08/1999
• Status: Expired due to Fees

• Current Assignee: Esoterix Genetic Laboratories LLC (Laboratory Corporation Of America Holdings)
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Shuber, Anthony P.
• Primary Examiner(s): Chunduru; Suryaprabha
• Application Number:
  US11/517,808
• Publication Number:
  US 20070202513A1
• Time in Patent Office: 1,496 Days
• Field of Search: 435/6, 435/91.2, 536/24.33, 536/23.1
• US Class Current: 435/6.12
• CPC Class Codes: C12Q 1/6881 for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574

Abstract

The present invention provides methods for detecting disease by analysis of a patient sample to determine the integrity of nucleic acids in the sample.

Claims

1. A method of detecting fetal abnormality, the method comprising the steps of:

conducting a plurality of amplification reactions on a nucleic acid to produce a plurality of nucleic acid fragments of different lengths, wherein the nucleic acid is obtained from maternal blood comprising fetal cells or fetal cellular debris;

qualitatively determining amplification level in the plurality of amplification reactions; and

identifying fetal abnormality if the qualitative amplification level is greater than a pre-determined threshold level.

2. The method of claim 1, wherein the fetal abnormality is associated with genomic instability.

3. The method of claim 1, wherein the step of qualitatively determining comprises:

assigning a binary score to each reaction such that the binary score indicates if a positive amplification takes place; and

determining a total score indicative of the amplification level for the plurality of amplification reactions based on the binary score in each reaction.

4. The method of claim 1, wherein the plurality of amplification reactions are conducted at a single genomic locus.

5. The method claim 1, wherein the plurality of amplification reactions are conducted on a plurality of different genomic loci.

6. The method of claim 1, wherein the pre-determined threshold level is the level of amplification determined in a normal sample.

7. The method of claim 1, wherein at least one amplified nucleic acid fragment is at least 200 bp in length.

8. The method of claim 1, wherein at least one amplified nucleic acid fragment is at least 400 bp in length.

9. The method of claim 1, wherein at least one amplified nucleic acid fragment is at least 800 bp in length.

10. The method of claim 1, wherein at least one amplified nucleic acid fragment is at least 1.3 Kb in length.

11. The method of claim 1, wherein at least one amplified nucleic acid fragment is at least 1.8 Kb in length.

12. The method of claim 1, wherein at least one amplified nucleic acid fragment is at least 2.4 Kb in length.