HiC: method of identifying interactions between genomic loci

Patent metadata

Field	Value
Publication number	US-9708648-B2
Application number	US-201615137988-A
Country	US
Kind code	B2
Filing date	Apr 25, 2016
Priority date	Sep 25, 2008
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

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 for identifying an interaction frequency, comprising;
a) providing;
i) a cell comprising at least one chromosome, wherein said at least one chromosome comprises a first region and a second region; and
ii) a junction marker;

b) extracting said at least one chromosome from said cell;
c) incorporating said junction marker into said extracted chromosome; and
d) identifying an interaction frequency between said first region and said second region.

2. The method of claim 1 , wherein said method further comprises fragmenting said at least one chromosome into fragments.

3. The method of claim 1 , wherein said junction marker comprises biotin.

4. The method of claim 1 , wherein said first and second regions are located on the same chromosome.

5. The method of claim 1 , wherein said first and second regions are located on different chromosomes.

6. The method of claim 1 , wherein said interaction frequency identifies a long range interaction.

7. The method of claim 1 , wherein said interaction frequency identifies a short range interaction.

8. The method of claim 1 , wherein said interaction frequency identifies a close neighbor interaction.

9. The method of claim 1 , wherein said at least one chromosome comprises a human chromosome.

10. The method of claim 1 , wherein said at least one chromosome comprises a yeast chromosome.

11. The method of claim 2 , further comprising digesting said chromosome fragments with a restriction endonuclease wherein a first region fragment comprising a first sticky end and a second region fragment comprising a second sticky end are created.

12. The method of claim 11 , further comprising filling in said first sticky end and said second sticky end to create a first blunt end and a second blunt end; and ligating said first and second blunt ends, wherein said first region and said second region are joined.

13. The method of claim 2 , further comprising digesting said chromosome fragments with an exonuclease.

Assignees

• Univ Massachusetts
• Massachusetts Inst Technology
• Harvard College
• Whitehead Inst Biomedical Res

Inventors

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

Classifications

• C12Q1/6837 Primary

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

• C12Q1/68 Primary

  involving nucleic acids · CPC title