# US 2014/0193817 A1 · Methods and kits useful for detecting an alteration in a locus copy number

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- Number: US 2014/0193817 A1
- Document ID: US20140193817A1
- Status: Published application
- Kind: A1
- Application number: 14/184,735
- Filed: 2014-02-20
- Published: 2014-07-10
- Earliest claimed: 2003-09-22
- Assignees: Trisogen Biotechnology Limited Partnership
- Applicants: Trisogen Biotechnology Limited Partnership
- Inventors: David HALLE
- Web page: https://patentgrep.com/patent/US20140193817A1

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 2600/154: Methylation markers
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

A method of identifying an alteration in a locus copy number is provided. The method is effected by determining a methylation state of at least one gene in the locus, wherein a methylation state differing from a predetermined methylation state of the at least one gene is indicative of an alteration in the locus copy number.

## Claims

### Claim 1

A method of identifying locus amplification, the method comprising determining a methylation state of at least one gene in the locus, said gene being selected having an expression pattern which is compatible with two gene copies, wherein an increase in methylation state of said at least one gene in the locus compared to a methylation state of said at least one gene in a non-amplified locus is indicative of locus amplification.

### Claim 2

A method of prenatally identifying locus amplification, the method comprising:
determining a methylation state of at least one gene at the locus in a prenatal chromosomal DNA, said gene being selected having an expression pattern which is compatible with two gene copies, wherein an increase in methylation state of said at least one gene in the locus compared to a methylation state of said at least one gene in a non-amplified locus is indicative of locus amplification in the prenatal subject.

### Claim 3

A method of prenatally testing Down's syndrome, the method comprising determining a methylation state of at least one gene in a prenatal chromosome 21, wherein said at least one gene is selected having an expression pattern which is compatible with two gene copies and whereas an increase in a state of said methylation of said at least one gene compared to a methylation state of said at least one gene in a non-amplified locus is indicative of amplification of said at least one gene, thereby prenatally diagnosing Down's syndrome.

### Claim 4 (depends on 3)

The method of claim 3, wherein said determining methylation state of said at least one gene is effected by:
(i) restriction enzyme digestion methylation detection;
(ii) bisulphate-based methylation detection;
(iii) mass-spectrometry analysis;
(iv) sequence analysis; and/or
(v) microarray analysis.

### Claim 5 (depends on 3)

The method of claim 3, wherein prenatal chromosomal DNA is obtained by:
(i) amniocentesis;
(ii) fetal biopsy;
(iii) chorionic villi sampling;
(iv) maternal biopsy;
(v) blood sampling;
(vi) cervical sampling; or
(vii) urine sampling.

### Claim 6 (depends on 3)

The method of claim 3, wherein said at least one gene is selected from the group consisting of C21Orf18, PKNOX1, APP (X127522), H2-calponin (gi:4758017), M28373, AF038175, AJ009610, AI830904, BE896159, AP000688, AB003151, NM—005441, AB004853, AA984919, AP001754, X99135, AI635289, AF018081, AI557255, BF341232, AL137757, AF217525, U85267, D87343, AA436684, NM—000830, NM—001535, D87328, X64072, AU137565, L41943, U05875, U05875, Z17227, AI033970, AI421115, AB011144, NM—002462, M30818, U75330, AF248484, Y13613, AB007862, AL041002, AA436452, BE795643, U73191, U09860, AP001753, BE742236, D43968, AV701741, BE501723, U80456, W55901, X63071, AI421041, NM—003895, D84294, AB001535, U75329, U61500, NM—004627, AL163300, AF017257, AJ409094, AF231919, NM—032910, NM—198155, AY358634, NM—018944, NM—001006116, NM—058182, NM—017833, NM—021254, NM—058187, NM—145328, NM—058188, NM—058190, NM—153750, AK001370, NM—017447, NM—017613, NM—003720, NM—016430, NM—018962, NM—004649, NM—206964, AK056033, NM—005534, NM—015259, NM—021219, NM—002240, AF432263, AF231919, AJ302080, NM—198996, NM—030891, NM—001001438, NM—032476, AJ002572, NM—013240, NM—021075, NM—138983, NM—005806, NM—002606, NM—003681, NM—015227, NM—058186, NM—58190, NM—58190, NM—004339, NM—144770, NM—020639, NM—020706, NM—005069, NM—194255, NM—018964, BC000036, NM—006948, AF007118, NM—080860, NM—006758, NM—006447, NM—013396, NM—018669, NM—018963, NM—004627, NM—015358, NM—015565, AJ409094, AF231919, NM—032910, NM—198155, AY358634, NM—018944, NM—001006116, NM—058182, NM—017833, NM—021254, NM 016940, NM—058187, NM—145328, NM—058188, NM—058190, NM—153750, AK001370, NM—017447, NM—017613, NM—003720, NM—016430, NM—018962, NM—004649, NM—206964, AK056033, NM—005534, NM—015259, NM—021219, NM—002240, AF432263, AF231919, AJ302080, NM—198996, NM—030891, NM—001001438, NM—032476, AJ002572, NM—013240, NM—021075, NM—138983, NM—005806, NM—002606, NM—003681, NM—015227, NM—058186, NM—58190, NM—58190, NM—004339, NM—144770, NM—020639, NM—020706, NM—005069, NM—194255, NM—018964, BC000036, NM—006948, AF007118, NM—080860, NM—006758, NM—006447, NM—013396, NM—018669, NM—018963, NM—004627, AK023825, NM—015358, NM—015565, NM—032195.1, NM—032261.3, NM-058181.1, NM-199071.2, NM—508188.1, NM 017445, NM 015056, RH25398, AF432264, NM 002388, NM 010925, NM 001008036, NM-024944.2, NM-017446,2 and NM—005806.1.