Hirschsprung’s disease affects the large intestine in the human body. This disease is caused by missing nerve cells in certain segments of the colon, which in turn brings about obstruction of bowel movement. If untreated, a patient may develop enterocolitis and this could lead to death. The only way to treat Hirschsprung’s disease is through surgery.

There is strong evidence linking this disease to genetic factors. More than eight genes have been found to be associated with the disease. The majority of the cases appear to be multigenic.

A study done by M. Ruiz-Ferrer et al (2008) described the Neurotrophic Factor 3 (NTF-3) gene as one of the causal genes in Hirschsprung’s disease. NTF-3 encodes for a protein growth factor which supports the survival and differentiation of neurons and synapses in the peripheral and central nervous systems. The SNP variation is postulated to produce immature functional NTF-3 proteins in neural crest cell precursors, in turn altering the NTF-3/TrkC signaling pathway and influencing inadequate Enteric Nervous System (ENS) development.

To view the mutation that occurs in NTF-3, please follow the instructions below:

  1. Click HERE and submit query.
  2. Click on the Score to view alignment.

Reference: Journal of pediatric surgery

Dengue fever has long been a menace in tropical and equatorial countries, including Africa, Malaysia, Thailand, India and Brazil. It remains one of the deadliest infectious diseases to date, having first struck as an epidemic in the 1950s. The World Health Organization reports that up to 2.5 billion people, constituting two fifths of the world’s population, are at risk from dengue. This staggering statistic is made even worse by current estimates that some 50 million people throughout the world are affected by dengue every year.

What is known of this lethal disease? For starters, dengue fever is caused by viruses transmitted by the Aedes mosquito, predominantly Aedes aegypti. These dengue viruses contain single stranded, positive sense RNA and belong to the genus Flavivirus, family Flaviviridae. There are four types of dengue viruses (classified as DEN-1 to DEN-4) which are immunologically related, yet different enough to not be affected by cross-protection. To date, there is no vaccine that offers protection against dengue viruses, and any vaccine developed must be able to immunise patients against all four serotypes effectively. This makes the early screening and identification of viral isolates even more vital.

One effective approach is to rapidly identify all the major and minor dengue serotypes using phylogenetics applications. This approach then makes it possible to design multivalent vaccines which could offer cross-protection against all dengue virus sub-types.

This process can be laborious and slow, as the genomes to be compared need to fetched and collated, after which pair-wise distance matrices need to be derived. In contrast, SynaTree™ provides an easy interface for collating the genomes to be compared, then rapidly generates distance measures from multi-comparisons, and provides an output file suitable for drawing phylogenetic trees. The collation and analysis of viral and bacterial genomes can be completed in a matter of minutes.

To generate a phylogenetic tree of new dengue viral strains using SynaTree, please follow the instructions below:

Stage 1: Generating a distance matrix using SynaTree

  1. Click HERE.
  2. Select the ‘Dengue Viral Genome’ database.
  3. Under the sequence expression box, type ‘dengue’ and select ‘List Sequence’. A list of all dengue viruses will appear in a box below.
  4. Click the ‘Add All’ button under the Sequence List header. All the sequences will be transferred to the box below, under the header ‘Selected Sequence’.
  5. Click ‘TREE’ to run the programme and wait for the data file to be generated.
  6. Once the results window appears, click ‘SAVE’ to save the results file on your computer.

Stage 2: Drawing a phylogenetic tree from the SynaTree data file

  1. If you do not already have SplitsTree on your computer, download and install the SplitsTree software from HERE.
  2. Open the SynaTree data file from the SplitsTree “Open” command.

Figure 1: The SplitsTree graph of the dengue phylogenetic tree using SynaTree

A major outbreak of hand-foot-mouth disease (HFMD) was recently reported in China. HFMD is caused by Enteroviruses such as EV71 or Coxsackie A16. Both viruses, however, lead to similar symptoms such as fever, mouth ulcers and a rash on the hands and feet. But unlike Coxsackie, EV71 infection can lead to encephalitis which can be fatal. Cases of fatal encephalitis occurred during outbreaks of HFMD in Malaysia in 1997 and in Taiwan in 1998.*

Genetically, EV71 is closely related to Coxsackie A16. To find sequence similarities between the two viruses, SynaCompare™ can be used to conduct a rapid and sensitive comparison. The dot-plot result shows a vague diagonal line, which indicates that there is limited homology between the two viruses. Potentially, these regions could be useful in identifying epitopes that can be targeted for cross-protective vaccine design against both viruses.

To run the comparison, please follow the instructions below:

  1. Click HERE and submit query.

Source: China View.

* Centres for Disease Control and Prevention

Back to Newsletters