US 12,006,547 B2
Detection of chromosome interactions as indicative of amyotrophic lateral sclerosis
Alexandre Akoulitchev, Oxford (GB); Aroul Selvam Ramadass, Oxford (GB); Ewan Hunter, Oxford (GB); and Matthew Salter, Oxford (GB)
Assigned to Oxford BioDynamics PLC, Oxford (GB)
Appl. No. 16/652,959
Filed by Oxford BioDynamics PLC, Oxford (GB)
PCT Filed Oct. 1, 2018, PCT No. PCT/GB2018/052808
§ 371(c)(1), (2) Date Apr. 1, 2020,
PCT Pub. No. WO2019/069067, PCT Pub. Date Apr. 11, 2019.
Claims priority of provisional application 62/566,756, filed on Oct. 2, 2017.
Prior Publication US 2020/0407790 A1, Dec. 31, 2020
Int. Cl. C12Q 1/6883 (2018.01)
CPC C12Q 1/6883 (2013.01) [C12Q 2600/106 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/156 (2013.01); C12Q 2600/158 (2013.01); C12Q 2600/178 (2013.01)] 2 Claims
OG exemplary drawing
 
1. A process for selecting a human individual and treating the selected human individual, wherein the selected human individual is in need of therapy for amyotrophic lateral sclerosis (ALS), wherein selecting the human individual is by:
detecting the absence of a first chromosome interaction,
detecting the presence of a second chromosome interaction,
detecting the presence of a third chromosome interaction,
detecting the presence of a fourth chromosome interaction,
detecting the presence of a fifth chromosome interaction,
detecting the absence of a sixth chromosome interaction,
detecting the absence of a seventh chromosome interaction,
detecting the absence of an eighth chromosome interaction,
detecting the presence of a ninth chromosome interaction,
detecting the absence of a tenth chromosome interaction,
detecting the absence of an eleventh chromosome interaction,
detecting the absence of a twelfth chromosome interaction,
detecting the presence of a thirteenth chromosome interaction,
detecting the presence of a fourteenth chromosome interaction,
detecting the presence of a fifteenth chromosome interaction,
detecting the presence of a sixteenth chromosome interaction, and
detecting the presence of a seventeenth chromosome interaction
in a sample from the human individual;
and treating the selected human individual for amyotrophic lateral sclerosis (ALS) by administering an agent which is therapeutic for amyotrophic lateral sclerosis (ALS);
wherein said detecting comprises:
(i) cross-linking of chromosome regions which have come together in a chromosome interaction;
(ii) subjecting said cross-linked regions to cleavage to form cross-linked cleaved nucleic acid;
(iii) ligating said cross-linked cleaved nucleic acid ends to form ligated nucleic acid; and
(iv) detecting the presence or absence of the ligated nucleic acid;
wherein:
the ligated nucleic acid corresponding to the first chromosome interaction is detected by the probe sequence
(SEQ ID NO: 2)
TCACCACACATCACCCCCTTGCTCCTCCTCGAGTCTTGGTGACCACAAC
AGGGTGCCACC,
the ligated nucleic acid corresponding to the second chromosome interaction is detected by the probe sequence
(SEQ ID NO: 3)
GAGGTGGGTGAATCATGAGGTCAAGGGTTCGACAATAGTTGAGAATCTC
CAACCACCTGG,
the ligated nucleic acid corresponding to the third chromosome interaction is detected by the probe sequence
(SEQ ID NO: 4)
GGCCTTATAGTCAGCTGATCAGGTGAAATCGATTGGTCCTTAGGATCAGC
 
TACCATTTGC,
the ligated nucleic acid corresponding to the fourth chromosome interaction is detected by the probe sequence
 (SEQ ID NO: 5)
GAGGCAGGCGGATCACAAAGTCAAAAGATCGATAACTTCAATAATAGTTA
 
CAGATGCAAA,
the ligated nucleic acid corresponding to the fifth chromosome interaction is detected by the probe sequence
 (SEQ ID NO: 6)
AGCACCATATCTGGGATGTAGCTATTGCTCGAGATTGCAGTGAGCTGTGA
 
TCACACCTCT,
the ligated nucleic acid corresponding to the sixth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 7)
TCTTCCCTCTTTTTAAAACCACCATTCATCGACCCCACACATCCTGTGCC
 
ACTCTACTGC,
the ligated nucleic acid corresponding to the seventh chromosome interaction is detected by the probe sequence
(SEQ ID NO: 8)
TAACCATTATGCATCACTAACATAGCATTCGATATGATATGCTCAGTTTA
 
GTTAGGGAAA,
the ligated nucleic acid corresponding to the eighth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 9)
GGCTCAGGAAGAGAACTATTTGTCTCTTTCGACACGCACATGCAGGACAC
 
TCACACGTAG,
the ligated nucleic acid corresponding to the ninth chromosome interaction is detected by the probe sequence
 (SEQ ID NO: 10)
GTTGGGTGGATCCCTTGAGCTCAGGAATTCGAAGAATGATTTTTCAGCCC
 
GTGTGGAAGG,
the ligated nucleic acid corresponding to the tenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 11)
ATCAAAAGAAAATAGATACTTGTCTTACTCGAGTTGAATAAAATCCTCAG
 
CTTTCTGTCC,
the ligated nucleic acid corresponding to the eleventh chromosome interaction is detected by the probe sequence
(SEQ ID NO: 12)
AAAAGAAACTGTGAAAAGTTGTCACATTTCGATTAAATCCAAAAAGGTCT
 
TCTATGAGGC,
the ligated nucleic acid corresponding to the twelfth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 13)
TTAAAAGTATAGTAGTTGGCATTAACATTCGACCTTTTTCTGTTTCAGTA
 
ACCAACCCAG,
the ligated nucleic acid corresponding to the thirteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 14)
CATCAACTAATAGTTAAACATTATAATATCGACTGAAGACCTTTCATACT
 
GTAAGATTCA,
the ligated nucleic acid corresponding to the fourteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 15)
CATCAACTAATAGTTAAACATTATAATATCGAGTCTGCAGTGAGCTGAGA
 
TCACACTGCC,
the ligated nucleic acid corresponding to the fifteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 16)
TTATTCCTTTCCAAATAGTTAAAATTATTCGAAACTTTTAAGAATCAATA
 
TAAAATTTCC,
the ligated nucleic acid corresponding to the sixteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 17)
CATAATTATAAATTAAAAAATGACACTATCGATTATGTCCAGTGTTTCTT
 
GGTTGGTGTC,
and
the ligated nucleic acid corresponding to the seventeenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 18)
CAGAGCACTAAGATAGACTTCTAAGGTTTCGAGGCATATAGCTCCAGCTG
 
TATTGAGGTA.