Further information about LACHESIS, including source code, documentation and a user's guide are available at: http://shendurelab.github.io/LACHESIS.

Manuscript describing LACHESIS was published as: Burton JN#, Adey A, Patwardhan RP, Qiu R, Kitzman JO, Shendure J#. Chromosome-scale scaffolding of de novo genome assemblies based on chromatin interactions. Nature Biotechnology 2013 Dec;31(12):1119-25. doi: 10.1038/nbt.272. PubMed PMID: 24185095.

http://shendurelab.github.io/LACHESIS/

Address of the bookmark: http://shendurelab.github.io/LACHESIS/

https://gold.jgi.doe.gov/

Address of the bookmark: https://gold.jgi.doe.gov/

https://www.hiv.lanl.gov/components/sequence/HIV/search/search.html

Address of the bookmark: https://www.hiv.lanl.gov/components/sequence/HIV/search/search.html

The NCBI Datasets datasets command line tools are datasets and dataformat .

Use datasets to download biological sequence data across all domains of life from NCBI.

Use dataformat to convert metadata from JSON Lines format to other formats.

Conda download:

https://anaconda.org/conda-forge/ncbi-datasets-cli

Buld Download

 https://www.ncbi.nlm.nih.gov/datasets/builder/?tax_id=29979

Address of the bookmark: https://www.ncbi.nlm.nih.gov/datasets/docs/v1/quickstarts/command-line-tools/

Address of the bookmark: https://github.com/CMU-SAFARI/AirLift

Address of the bookmark: https://www.science.org/doi/10.1126/science.abj6987

What Are Chromosome Rearrangements?

Chromosome rearrangements are structural changes that alter the normal configuration of chromosomes. These changes can involve large segments of DNA — from thousands to millions of base pairs — and can occur spontaneously, be inherited, or result from exposure to mutagens (like radiation or chemicals).

Common Types of Rearrangements:

1. Deletions – Loss of a chromosome segment

2. Duplications – Repetition of a segment

3. Inversions – A segment breaks off, flips, and reattaches

4. Translocations – Segments exchange places between non-homologous chromosomes

5. Insertions – A segment is inserted into another part of the genome

These changes can disrupt genes directly or affect gene regulation, leading to disease.

How Do Chromosome Rearrangements Cause Disease?

The impact of a rearrangement depends on which genes are involved, how much DNA is affected, and when the rearrangement occurs (in development vs. adulthood). Here are some key mechanisms:

• Gene disruption: Breaking a gene can lead to loss of function or the creation of a non-functional protein.

• Gene fusion: Joining parts of two genes may form a novel hybrid gene with new functions (common in cancer).

• Dosage effects: Extra or missing gene copies can disturb the balance of gene expression.

• Position effects: Moving a gene to a new regulatory environment may silence or over-activate it.

Chromosome Rearrangements in Human Disease

1. Developmental Disorders

• Cri-du-chat syndrome: Caused by a deletion on chromosome 5p. Affected infants often have a high-pitched cry and intellectual disability.

• Williams syndrome: Results from a microdeletion on chromosome 7q, affecting genes related to cardiovascular and cognitive function.

2. Cancer

Cancer is perhaps the most striking example of disease caused by chromosome rearrangements.

• Chronic Myeloid Leukemia (CML): Caused by a translocation between chromosomes 9 and 22, forming the Philadelphia chromosome. This creates the BCR-ABL fusion gene, which drives uncontrolled cell growth.

• Burkitt lymphoma: Involves translocation of the MYC gene, leading to excessive cell division.

• Ewing sarcoma: A fusion of EWSR1 and FLI1 genes through translocation promotes tumor development.

3. Infertility and Miscarriages

Balanced rearrangements (like inversions or translocations) in carriers may not cause disease directly but can result in:

• Recurrent miscarriages

• Infertility

• Birth defects in offspring

Detecting Rearrangements

Thanks to modern genomics, chromosome rearrangements can now be detected with high precision using:

• Karyotyping – Classic method for detecting large rearrangements

• FISH (Fluorescence In Situ Hybridization) – Uses fluorescent probes to target specific DNA sequences

• Array CGH (Comparative Genomic Hybridization) – Detects copy number changes across the genome

• Whole Genome Sequencing (WGS) – Identifies even small or complex rearrangements at base-pair resolution

Looking Forward: The Future of Chromosome Medicine

Understanding chromosome rearrangements is now central to:

• Personalized medicine

• Genetic counseling

• Targeted therapies, especially in cancer (e.g., tyrosine kinase inhibitors for BCR-ABL fusion)

With the rise of long-read sequencing and single-cell genomics, even previously “invisible” rearrangements are being uncovered, offering new insights into both rare diseases and common conditions.

Final Thoughts

Chromosome rearrangements remind us that genetics isn't just about which genes we have — but where they are, how they're arranged, and when they're active. As our tools grow sharper, so does our ability to diagnose, understand, and treat diseases rooted in genomic architecture.

In a way, the genome is like a book not just defined by its words, but also by how the chapters are ordered. Rearranging them can create a new story — sometimes harmful, sometimes insightful — and understanding these changes is key to writing a healthier future.

Further information about fragScaff, including source code, is available at:https://sourceforge.net/projects/fragscaff/files.

Manuscript describing fragScaff was published as: Adey A, Kitzman JO, Burton JN, Daza R, Kumar A, Christiansen L, Ronaghi M, Amini S, L Gunderson K, Steemers FJ, Shendure J#. In vitro, long-range sequence information for de novo genome assembly via transposase contiguity. Genome Research 2014 Dec;24(12):2041-9. doi: 10.1101/gr.178319.114. PubMed PMID: 25327137.

Address of the bookmark: https://sourceforge.net/projects/fragscaff/files/

Address of the bookmark: https://www.encodeproject.org/data-standards/reference-sequences/

We have sequenced the CHM13hTERT human cell line with a number of technologies. Human genomic DNA was extracted from the cultured cell line. As the DNA is native, modified bases will be preserved. The data includes 30x PacBio HiFi, 120x coverage of Oxford Nanopore, 70x PacBio CLR, 50x 10X Genomics, as well as BioNano DLS and Arima Genomics HiC. Most raw data is available from this site, with the exception of the PacBio data which was generated by the University of Washington/PacBio and is available from NCBI SRA.

A UCSC browser is available for v2.0 (as well as legacy v1.0 and v1.1 versions). An interactive dotplot visualization of all genomic repeats is also available from resgen.io. Known issues identified in the assembly are tracked at CHM13 issues.

MORE at https://github.com/marbl/CHM13

Address of the bookmark: https://www.science.org/doi/10.1126/science.abj6987