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.

To address the challenges of describing and estimating virodiversity, a team of investigators from Center for Infection and Immunity (CII) and EcoHealth Alliance began in jungles of Bangladesh - home to the flying fox.

Reference:

http://economictimes.indiatimes.com/news/news-by-industry/et-cetera/mammals-harbour-at-least-320000-new-viruses/articleshow/22253268.cms

http://www.bbc.co.uk/news/science-environment-23932400

Now a day, geneticists have developed a language of their own. They are pouring lots of money and energy to read the entire genomic text and understand the gods own code ATGC. It is somewhat fascinating, not only for geneticist but also for non-biologist to know that there are several conserved blocks in genome which remain conserved over hundreds of millions of years. There have been several researches on conserved blocks and non-conserved regions to understand the mechanism and importance of all these regions (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675965/). The finding indicates conservation and rearrangements of certain evolutionary important genes play an important role in evolution/adaptive changes (http://www.nature.com/nature/journal/v491/n7424/abs/nature11622.html https://academic.oup.com/gbe/article/8/8/2442/2198198/Novel-Insights-into-Chromosome-Evolution-in-Birds , http://science.sciencemag.org/content/346/6215/1311).

But the puzzle remains open, how to correctly define the synteny (presence of two or more genes on the same chromosome) and conserved synteny (presence of two or more genes on chromosome of each of the two species) on several genomes.

Figure: Image generated with Evolution Highway (EH) tool http://eh-demo.ncsa.illinois.edu/ 

Keeping the new approach to define conserved synteny in mind there have been various algorithms developed to identify the conserved homologous synteny blocks (HSB) amongst species. Some of them which were commonly used for synteny detections are:

SyntenyTracker ( http://www-app.igb.uiuc.edu/labs/lewin/donthu/Synteny_assign/html/),

SyntenyTracker was shown to be an efficient and accurate automated tool for defining HSBs using datasets that may contain minor errors resulting from limitations in map construction methodologies.

CoGe (http://genomevolution.org/CoGe/SynFind.pl )

Satsuma (http://evomics.org/learning/genomics/satsuma/)

Cinteny (http://cinteny.cchmc.org/) ,

Cinteny server can be used for finding regions syntenic across multiple genomes and measuring the extent of genome rearrangement using reversal distance as a measure.

OrthoCluster (http://krono.act.uji.es/noticias/orthocluster-a-new-tool-for-mining-syntenic-blocks)

A new tool for mining syntenic blocks in comparative genomics

SynMap (http://genomevolution.org/wiki/index.php/SynMap),

SyMAP (http://www.symapdb.org/)

SyMAP (Synteny Mapping and Analysis Program) v4.0 is an automated system for identifying and displaying genome synteny alignments. The genomes may be represented by sequenced chromosomes (pseudomolecules), by draft sequence contigs, or by FPC physical maps (with BAC-end or marker sequence).

http://genomevolution.org/CoGe/SynMap.pl

RegionMiner (http://www.genomatix.de/online_help/help_regionminer/orthologous.html)

SyntenyMiner is being developed as an application to visualize and interrogate comparisons among multiple complete genome sequences. http://syntenyminer.sourceforge.net/

AutoGRAPH ( http://autograph.genouest.org/),

AutoGRAPH is an integrated web server for multi-species comparative genomic analysis. It is designed for constructing and visualizing synteny maps between two or three species, determination and display of macrosynteny and microsynteny relationships among species, and for highlighting evolutionary breakpoints.

SynChro(http://www.lgm.upmc.fr/CHROnicle/SynChro.html)

SynChro is a tool designed to define conserved synteny blocks. It reconstructs synteny blocks between pairwise comparison of multiple genomes. The reconstructed synteny blocks may overlap each other, be included in one another or duplicated due to micro-rearrangements.

SyntenyView ( http://www.cbs.dtu.dk/dtucourse/cookbooks/nikob/exercises/gf1_output_5.html),

Ensembl 'SyntenyView' shows conservation of large-scale gene order between species pairs. A brief summary of the calculation method appears at the bottom of this help page.  The left of a 'SyntenyView' page displays a diagram of chromosomes with blocks of conserved synteny. The right of a page shows homology matches between individual genes within syntenic blocks.

SynBrowse ( http://www.synbrowse.org/),

SynBrowse (Synteny Browser) is a generic sequence comparison tool for visualizing genome alignments both within and between species. It is intended to help scientists study and analyze synteny, homologous genes and other conserved elements between sequences. This software is useful in studying genome duplication and evolution. It can also aid in identifying uncharacterized genes, putative regulatory elements and novel structural features of study species by comparing to a well annotated reference sequence, thus enabling genome curators to refine and edit annotations of species that have incomplete genome annotations.

Sibelia (http://arxiv.org/abs/1307.7941).

A comparative genomic tool: It assists biologists in analysing the genomic variations that correlate with pathogens, or the genomic changes that help microorganisms adapt in different environments. Sibelia will also be helpful for the evolutionary and genome rearrangement studies for multiple strains of microorganisms.

GSV (http://cas-bioinfo.cas.unt.edu/gsv/homepage.php)

Genome Synteny Viewer allows users to upload files which contain synteny regions between two or more genomes and interactively visualize the synteny between them. GSV also allows users to upload annotation files to visualize annotated regions in addition to synteny regions.

MicroSyn (http://www.lgm.upmc.fr/CHROnicle/SynChro.html)

MicroSyn software as a means of detecting microsynteny in adjacent genomic regions surrounding genes in gene families. MicroSyn searches for conserved, flanking colinear homologous gene pairs between two genomic fragments to determine the relationship between two members in a gene family.

SynOrth (http://synorth.genereg.net/)

Synorth [s n ôrth], named in combination of "synteny" and "ortholog", is designed for the study of evolutionary changes of genomic regulatory blocks (GRBs) in vertebrate genomes, and especially the changes following the whole-genome duplication in teleost fish, by tracing the ortholog genes gain and loss in ancient synteny blocks.

SyDiG (http://www.ncbi.nlm.nih.gov/pubmed/21441096)

Uncovering Synteny in Distant Genomes.

MapSynteny  (http://www.automatizacionysistemas.com/download.html)

MapSynteny is a macro in MS Excel® able to create images to show the relationship between genetic maps and large sequences (scaffolds, chromosomes, BACs, etc.). Based on tab – delimited BLAST results and some formulas, a suitable image of syntenic relationships or physical mapping can be obtained. http://www.automatizacionysistemas.com/Poster_MapSynteny.pdf

One of the best synteny tutorial for beginer @ http://www.nature.com/scitable/topicpage/synteny-inferring-ancestral-genomes-44022

Reference:

http://www.nature.com/scitable/topicpage/synteny-inferring-ancestral-genomes-44022

http://www.nature.com/nature/journal/v491/n7424/full/nature11622.html

http://en.wikipedia.org/wiki/Synteny

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675965/

Following are the list of journals publishing pint-sized articles go by various names, such as genome reports, genome announcements, genome notes or genome letters, but will be referred to here broadly as genome reports.

1. Genome Announcements, American Society for Microbiology, Genome announcement, Impact factor 1.3,  A 500-word report stating that the genome of a particular organism (prokaryote, eukaryote or virus) has been sequenced and providing a citable record of the corresponding GenBank submission. Must include abstract but no text headings can be used except for ‘Acknowledgments’ and ‘References’. Cannot include figures, tables or supplemental material to present data or analysis.

Link: https://mra.asm.org/

2. Genome Biology and Evolution, Oxford University Press, Genome report, Impact factor 4.2, Focused 1500-word papers (up to six tables or figures) that publish the main evolutionary message of new genome sequences as they become submitted to GenBank. May also contain specifically focused comparative analyses of previously published genomes that contain a substantial and novel insight of broadest evolutionary significance.

Link: https://academic.oup.com/gbe

3. Journal of Biotechnology, Elsevier, Genome announcement, Impact factor 2.9, A 500-word report announcing the availability of the completely annotated genome sequence of a biotechnologically relevant organism in the corresponding database (for eukaryotes, advanced draft genomes will also be considered). Articles can contain an Abstract, a brief report on the organism and its biotechnological relevance, a table summarizing the genome features, References and an Acknowledgement. Figures are generally not allowed.

Link: https://www.journals.elsevier.com/journal-of-biotechnology

4. Journal of Genomics, Ivyspring, Genome note, Impact factor N/A, A 1000-word report (10 reference limit; conclusions not permitted) describing novel data sets from high-throughput analysis of genotypes, phenotypes, gene expression, metabolomes, proteomes or genome assemblies.Standard metrics for data quality and the experimental design must be clearly reported.

Link: http://www.jgenomics.com/

5. Memórias do Instituto, Oswaldo Cruz Oswaldo Cruz Foundation, Genome announcement and highlight, Impact factor 1.6, Dedicated to publishing new genome information from eukaryote parasites, virus, bacteria and their respective vectors, as well as re-sequencing or comparative genome analyses. Should occupy no more than three printed pages including figures and/or tables.

Link: http://memorias.ioc.fiocruz.br/

6. Molecular Ecology Resources, Wiley, Genomic resources note,  Impact factor 3.7, Short notes on newly assembled and annotated transcriptomes, genome fractions or whole genomes, and/or a library of SNP/SSR markers.Authors submit a short manuscript describing how the resource was developed and where the data can be accessed. Do not appear in journal as individual papers but are instead published as part of a summary article.

Link: https://onlinelibrary.wiley.com/journal/17550998

7. Standards in Genomic Science, BioMed Central (Springer), Short genome report, Impact factor 3.2, Short (∼500-word) article on newly sequenced genome. Article format must follow guidelines and template (available from journal Web site) put forward by the SGS. Any manuscripts not using template or that are missing key figures, tables and/or references (as per the guidelines) will be returned to authors. Rationale of the content model is to provide information that is consistently and uniformly presented for rapid and easy consumption by both human and machine readers. 

Link: https://standardsingenomics.biomedcentral.com/

8. 3biotech, Springer, Short genome report, Impact factor 1.3, Short (∼500-word) article on newly sequenced genome. Article format must follow guidelines (available from journal Web site).  Genome of a particular organism (prokaryote, eukaryote or virus) has been sequenced and providing a citable record of the corresponding GenBank submission.

Link: https://link.springer.com/journal/13205

Name of the post: Senior Research Fellow (SRF)
Duration: 2 year
Salary: Rs. 28000/- per month + 30% HRA
Eligibility: MSc (life sciences) with 2 years research experience, NET/GATE qualified
Desirable: Experience in the field of Genomics, Epigenomics & Bioinformatics
SELECTION PROCEDURE FOR ALL INDIA INSTITUTE OF MEDICAL SCIENCES (AIIMS DELHI) – SENIOR RESEARCH FELLOW POST:

Candidates can apply on or before 15/03/2015
No Detailed information about the selection process is mentioned in the recruitment notification
HOW TO APPLY FOR SENIOR RESEARCH FELLOW VACANCY IN ALL INDIA INSTITUTE OF MEDICAL SCIENCES (AIIMS DELHI):

Deadline: 15.03.15 Submit your C.V in Room No. 2099 (Molecular Cytogenetics Lab), 2nd floor, Reproductive Biology, All India Institute of Medical Sciences, New Delhi-110029 or Email CV to: ashutoshhalder@gmail.com Your CV should include the details of your work experience & degrees along with two references with e-mail and contact number Only 10 shortlisted (on merit) candidates will be invited for interview. No TA/DA will be applicable for the same

Address of the bookmark: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783527/

https://www.crick.ac.uk/research/labs/charles-swanton

1. How to perform basic quality checks on the input data
2. How to run a short read assembler on Illumina data
3. How to run a long read assembler on Pacific Biosciences or Oxford Nanopore data
4. How to improve the accuracy of a long read assembly using short reads
5. How to assess the quality of an assembly

https://bioinformaticsdotca.github.io/high-throughput_biology_2017

Address of the bookmark: https://bioinformaticsdotca.github.io/high-throughput_biology_2017_module6_lab