Detection of chromosome interactions as indicative of amyotrophic lateral sclerosis

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.

2. The process according to claim 1 wherein the detecting comprises specific detection of the ligated nucleic acid by quantitative PCR (qPCR), wherein the probe comprises:

a fluorophore covalently attached to the 5′ end of the probe, and/or

a quencher covalently attached to the 3′ end of the probe.