HiC: method of identifying regulatory interactions between genomic loci

Patent metadata

Field	Value
Publication number	US-12146186-B2
Application number	US-202016990543-A
Country	US
Kind code	B2
Filing date	Aug 11, 2020
Priority date	Sep 25, 2008
Publication date	Nov 19, 2024
Grant date	Nov 19, 2024

Abstract

The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.

First claim

The invention claimed is:

1. A method, comprising;
a) providing;
i) a crosslinked mammalian genome comprising a plurality of joins, wherein the each of said plurality of joins comprises two ligated nucleic acid sequences; and
ii) a plurality of paired end sequencing adaptors;

b) ligating said plurality of paired end sequencing adaptors to the said plurality of joins;
c) sequencing each of said two ligated nucleic acid sequences with said plurality of paired end sequencing adaptors; and
d) aligning each of said sequenced two ligated nucleic acid sequences to have identity with a first genomic region and a second genomic region on a mammalian genome reference sequence;
e) detecting a regulatory element within said second genomic region that interacts with said first genomic region.

2. The method of claim 1 , wherein said crosslinked mammalian genome comprises a crosslinked human genome.

3. The method of claim 1 , wherein said crosslinked mammalian genome comprises a crosslinked non-human genome.

4. The method of claim 1 , wherein said first genomic region comprises an open reading frame sequence.

5. The method of claim 1 , wherein said second genomic region comprises a regulatory gene.

6. The method of claim 5 , wherein said regulatory gene interacts with said open reading frame sequence.

7. The method of claim 4 , wherein said open reading frame sequence encodes a protein associated with a medical condition.

8. The method of claim 7 , wherein said medical condition comprises cancer.

9. The method of claim 7 , wherein said medical condition comprises a cardiovascular disease.

10. The method of claim 7 , wherein said medical condition comprises a kidney disease.

11. The method of claim 7 , wherein said medical condition comprises an autoimmune disease.

12. The method of claim 7 , wherein said medical condition comprises a pulmonary disease.

13. The method of claim 7 , wherein said medical condition comprises a pancreatic disease.

14. The method of claim 7 , wherein said medical condition comprises a muscular disease.

15. The method of claim 7 , wherein said medical condition comprises a bone disease.

16. The method of claim 7 , wherein said medical condition comprises a blood disorder.

17. The method of claim 7 , wherein said medical condition comprises a sleep disorder.

18. The method of claim 5 , wherein said regulatory gene comprises an enhancer.

19. The method of claim 5 , wherein said regulatory gene comprises a silencer.

20. The method of claim 5 , wherein said regulatory gene comprises an insulator.

Assignees

• Univ Massachusetts
• Massachusetts Inst Technology
• Harvard College
• Whitehead Inst Biomedical Res
• Presidents And Fellows Of Harvard Univ

Inventors

• Dekker Job
• Aiden Erez Lieberman
• Van Berkum Nynke
• Gnirke Andreas
• Lander Eric
• Nusbaum Chad
• Williams Louise
• Melnikov Alexandre
• Giannoukos Georgia

Classifications

• C12Q1/68 Primary

  involving nucleic acids · CPC title

• C12Q1/6837 Primary

  using probe arrays or probe chips (C12Q1/6874 takes precedence) · CPC title