BOL: Related items

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.

Landry Lab

Thu, 17 Jul 2014 14:33:57 -0500

EVOLUTIONARY AND INTEGRATIVE CELL BIOLOGY

Our research is at the crossroad between cell biology, ecological genomics, systems biology, molecular evolution and population genetics. We study the architecture and evolution of protein and signalling networks.

More at http://landrylab.ibis.ulaval.ca/

320000 viruses in mammals yet to sequenced in future!!!

Rahul Agarwal — Tue, 03 Sep 2013 08:35:30 -0500

With current biological technique improvements, finally it is now possible to look at millions of unknown viruses at genomic level and understand the mechanism. According to available data, close to 70 per cent of emerging viral diseases such as HIV/AIDS, West Nile, Ebola, SARS, and influenza, are zoonoses - infections of animals that cross into humans.

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

J. Aires de Sousa Research Group

Wed, 12 Mar 2014 09:57:25 -0500

We are involved in the development of methods and software in chemoinformatics. Current main projects are:

1.automatic learning of chemical reactivity and metabolism,
2.simulation of NMR spectra,
3.modelling of properties of ionic liquids, and
4.representation of molecular chirality.

More at http://joao.airesdesousa.com/

Tools to detect synteny blocks regions among multiple genomes

Jitendra Narayan — Mon, 16 Sep 2013 17:12:02 -0500

The synteny block (which etymologically means “on the same ribbon”) is a collection of contiguous genes located on the same chromosome. These block regions have mostly been preserved by genome rearrangements, and so synteny blocks from two related species (e.g., humans and mice) will be roughly similar but flipped around on the respective genomes. Ovcharenko et. al. define it as ‘any conserved sequence blocks, regardless of whether it encompasses multiple genes, an area containing single genes, or areas devoid of known genes to be considers as synteny block as long as there is conservation at the sequence level. Today, however, biologists usually refer to synteny as the conservation of blocks of order within two sets of chromosomes that are being compared with each other. This concept can also be referred to as shared synteny. The NHBLI/NCBI Glossary define synteny as “Two genes which occur on the same chromosome are syntenic; however, syntenic genes may or may not be "linked."

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/

Linux SSH Client Commands for Bioinformatics

Rahul Nayak — Thu, 13 Mar 2014 17:16:32 -0500

Here come on let play with the following basic command line usage of the ssh client.

1. Check your SSH Client Version:

Checking for your SSH client is very sare, but sometimes it may be necessary to identify the SSH client that you are currently running and it’s corresponding version number. The SSh client can be identified as follows

$ ssh -V
OpenSSH_3.9p1, OpenSSL 0.9.7a Feb 19 2013

$ ssh -V
ssh: SSH Secure Shell 3.2.9.1 (non-commercial version) on i686-pc-linux-gnu

2. Connect and login to remote host:

The First time when you login to the remotehost from a localhost, it will display the host key not found message and you can give “yes” to continue. The host key of the remote host will be added under .ssh2/hostkeys directory of your home directory, as shown below.

localhost$ ssh -l jit remotehost.example.com

jit@remotehost.example.com password:

remotehost.example.com$

The Second time when you login to the remote host from the localhost, it will prompt only for the password as the remote host key is already added to the known hosts list of the ssh client.

localhost$ ssh -l jit remotehost.example.com
jit@remotehost.example.com password:
remotehost.example.com$

For some reason, if the host key of the remote host is changed after you logged in for the first time, you may get a warning message as shown below. This could be because of various reasons such as 1) Sysadmin upgraded/reinstalled the SSH server on the remote host 2) someone is doing malicious activity etc., The best possible action to take before saying “yes” to the message below, is to call your sysadmin and identify why you got the host key changed message and verify whether it is the correct host key or not.

localhost$ ssh -l jit remotehost.example.com

jit @remotehost.example.com's password:
remotehost$

4. Debug SSH Client:

Sometimes it is necessary to view debug messages to troubleshoot any SSH connection issues. For this purpose, pass -v (lowercase v) option to the ssh as shown below.

Example without debug message:

        localhost$ ssh -l jit remotehost.example.com
        warning: Connecting to remotehost.example.com failed: No address associated to the name
        localhost$

Example with debug message:

        locaclhost$ ssh -v -l jit remotehost.example.com
        debug: SshConfig/sshconfig.c:2838/ssh2_parse_config_ext: Metaconfig parsing stopped at line 3.
        debug: SshConfig/sshconfig.c:637/ssh_config_set_param_verbose: Setting variable 'VerboseMode' to 'FALSE'.
        debug: SshConfig/sshconfig.c:3130/ssh_config_read_file_ext: Read 17 params from config file.
        debug: Ssh2/ssh2.c:1707/main: User config file not found, using defaults. (Looked for '/home/jit/.ssh2/ssh2_config')
        debug: Connecting to remotehost.example.com, port 22... (SOCKS not used)
        warning: Connecting to remotehost.example.com failed: No address associated to

5. Escape Character: (Toggle SSH session, SSH session statistics etc.)

Escape character ~ get’s SSH clients attention and the character following the ~ determines the escape command.
Toggle SSH Session: When you’ve logged on to the remotehost using ssh from the localhost, you may want to come back to the localhost to perform some activity and go back to remote host again. In this case, you don’t need to disconnect the ssh session to the remote host. Instead follow the steps below.

i. Login to remotehost from localhost: localhost$ssh -l jit remotehost
ii. Now you are connected to the remotehost: remotehost$
iii. To come back to the localhost temporarily, type the escape character ~ and Control-Z. When you type ~ you will not see that immediately on the screen until you press and press enter. So, on the remotehost in a new line enter the following key strokes for the below to work: ~

    remotehost$ ~^Z
    [1]+ Stopped                 ssh -l jit remotehost
    localhost$

iv. Now you are back to the localhost and the ssh remotehost client session runs as a typical unix background job, which you can check as shown below:

    localhost$ jobs
    [1]+ Stopped                 ssh -l jit remotehost

v. You can go back to the remote host ssh without entering the password again by bringing the background ssh remotehost session job to foreground on the localhost

    localhost$ fg %1
    ssh -l jit remotehost
    remotehost$

Bioinformatician duties and jobs !!!

Jitendra Narayan — Wed, 05 Mar 2014 14:32:26 -0600

Needle in a haystack ... ohh yes this is what bioinformatician do. We handle and analyse, Terabytes and Petabytes of genomic data on daily basis.

Basic Notions in Molecular Biology and Genetics

Antony Campos — Sun, 16 Mar 2014 18:15:29 -0500

This is a presentation about some fundamental concepts applied in molecular biology and genetics, also it contains a little bit of the experience that one of our members has gained in his years of undergraduate state related to molecular cloning. Our research group, called "BIOPHARM" (Acronymus of Laboratory of Bioinformatics and Pharmacogenetics), was stablished on 2007, took it a bit of years to make it real this initative, although, nowadays, we're working on some projects involved in those fields. This research group belongs to the Department of Biochemistry, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima, Perú. We try to encourage research initiatives, helping them and also we use to participate in differents courses, congress and symposiums.

Alignment of closely related whole genomes/scaffolds

Rahul Nayak — Fri, 29 Jan 2016 10:37:27 -0600

With the relative ease and low cost of current generation sequencing technologies has led to a dramatic increase in the number of sequenced genomes for species across the tree of life. This increasing volume of data requires tools that can quickly compare multiple whole-genome sequences, millions of base pairs in length, to aid in the study of populations, pan-genomes, and genome evolution.This bookmaks have been created to report new tools for whole genome alignments.

Please report new whole genome alignment tools under comment sections.

Address of the bookmark: http://www.cs.utoronto.ca/~brudno/721.full.pdf

Gerstein Lab

Wed, 19 Mar 2014 12:48:20 -0500

The focus of the Gerstein Lab is interpreting personal genomes, particularly in relation to disorders, such as cancer. This endeavor has a number of related aspects described below. Moreover, the approaches we take have broad connections to a variety of data-intensive fields, within the emerging discipline of data science.

Personal Genome Variation: SVs
Human Genome Annotation: Processing Next-Gen Sequencing Data
Comparative Genomics: Pseudogenes as Molecular Fossils
Protein Structure and Function: Macromolecular Motions
Analysis of Diverse Networks
Genomics at the Forefront of Data Science

Lab page: http://www.gersteinlab.org/