BOL: Related items

Alien_Hunter : prediction of putative Horizontal Gene Transfer (HGT) events

Jit — Sun, 07 Jan 2018 19:11:18 -0600

Alien_hunter is an application for the prediction of putative Horizontal Gene Transfer (HGT) events with the implementation of Interpolated Variable Order Motifs (IVOMs).

An IVOM approach exploits compositional biases using variable order motif distributions and captures more reliably the local composition of a sequence compared to fixed-order methods. Optionally the predictions can be parsed into a 2-state 2nd order Hidden Markov Model (HMM), in a change-point detection framework, to optimize the localization of the boundaries of the predicted regions. The predictions (embl format) can be automatically loaded into the freely available Artemis genome viewer.

Address of the bookmark: http://www.sanger.ac.uk/science/tools/alien-hunter

Ribbon !!

Jit — Fri, 21 Oct 2016 04:54:30 -0500

Visualization has played an extremely important role in the current genomic revolution to inspect and understand variants, expression patterns, evolutionary changes, and a number of other relationships. However, most of the information in read-to-reference or genome-genome alignments is lost for structural variations in the one-dimensional views of most genome browsers showing only reference coordinates. Instead, structural variations captured by long reads or assembled contigs often need more context to understand, including alignments and other genomic information from multiple chromosomes. We have addressed this problem by creating Ribbon (genomeribbon.com) an interactive online visualization tool that displays alignments along both reference and query sequences, along with any associated variant calls in the sample. This way Ribbon shows patterns in alignments of many reads across multiple chromosomes, while allowing detailed inspection of individual reads (Supplementary Note 1). For example, here we show a gene fusion in the SK-BR-3 breast cancer cell line linking the genes CYTH1 and EIF3H. While it has been found in the transcriptome previously, genome sequencing did not identify a direct chromosomal fusion between these two genes. After SMRT sequencing, Ribbon shows that there are indeed long reads that span from one gene to the other, going through not one but two variants, for the first time showing the genomic link between these two genes (Figure 1a). More gene fusions of this cancer cell line are investigated in Supplementary Note 2. Figure 1b shows another complex event in this sample made simple in Ribbon: the translocation of a 4.4 kb sequence deleted from chr19 and inserted into chr16 (Figure 1b). Thus, Ribbon enables understanding of complex variants, and it may also help in the detection of sequencing and sample preparation issues, testing of aligners and variant-callers, and rapid curation of structural variant candidates (Supplementary Note 3). In addition to SAM and BAM files with long, short, or paired-end reads, Ribbon can also load coordinate files from whole genome aligners such as MUMmer. Therefore, Ribbon can be used to test assembly algorithms or inspect the similarity between species. Supplementary Note 4 shows a comparison of gorilla and human genomes using Ribbon, highlighting major structural differences. In conclusion, Ribbon is a powerful interactive web tool for viewing complex genomic alignments.

Script at https://github.com/MariaNattestad/ribbon

Address of the bookmark: http://genomeribbon.com/

SVfinder: Tool for detecting genomic rearrangement form DNA-seq data

Robert M Willioms — Thu, 14 Dec 2017 15:51:40 -0600

SVfinder provides genome-wide detection of structural variants from next generation paired-end sequencing reads.

Address of the bookmark: https://github.com/cauyrd/SVfinder

When Chromosomes Shift: Understanding Chromosome Rearrangement and Human Disease

BioStar — Fri, 11 Apr 2025 01:07:17 -0500

In the vast and complex world of genetics, our chromosomes are like carefully arranged bookshelves — each holding critical information that defines who we are. But what happens when those books are shuffled, inverted, or swapped? The answer lies in a phenomenon known as chromosome rearrangement, a powerful force behind many human diseases, from developmental disorders to cancer.

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:

Deletions – Loss of a chromosome segment
Duplications – Repetition of a segment
Inversions – A segment breaks off, flips, and reattaches
Translocations – Segments exchange places between non-homologous chromosomes
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.