Newly discovered CLU gene involved in Alzheimer’s Disease
Incurable. Progressively degenerative. Terminal.
Alzheimer’s Disease (AD) is the most common form of dementia, a highly damaging brain disorder. Until recently, only one gene, APOE4, had been shown to be associated with AD, and this was way back in 1993. However, in June this year, three new genes – CLU, CR1 and PICALM were discovered through an AD genome-wide association study. A discovery that has researchers quietly optimistic about better understanding AD.
The CLU gene encodes a protein called clusterin which is associated with the clearance of cellular debris such as amyloid. Levels of clusterin tend to rise in order to protect the brain when the brain tissue becomes inflamed or injured. Mutations within CLU may remove the protective benefit of clusterin. There is a high probability this could lead to AD, which is partially characterised by a buildup of amyloid protein plaques in brain tissue.
In the course of their study, the researchers also discovered 13 other genes with possible links to AD which could potentially lead to the development of treatment for this disease.
Using SynaTate™, it can be seen that the potentially active region of CLU is on the third forward reading frame and searching this region using SynaSearch™ reveals significant homologies to clusterin in several different species. Having homologies to different species opens up doors for in vivo mutation studies of CLU expression in well known animal models such as mice.
SynaTate and SynaSearch can also be used to analyse the CR1 and PICALM genes.
Journal Reference: Nature Genetics
Step 1 of 5
Click here, then click on .
Step 2 of 5
On the results page, select the region that shows high SIGNIFICANCE by holding the left-click and dragging it across the entire selection as shown.

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Right click inside the selected region to view options available.
Select Search nucleotide sequence.

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Select Nucleotide-protein for the query type. Under the Target database panel, click on the dropdown menu bar and select Swiss-Prot UPKB Release 57.8.
Then click on the ‘Submit query‘ button.

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The results show that the SIGNIFICANCE region of CLU matches clusterin which has homology in many species including the European rabbit (Oryctolagus cuniculus), horse (Equus caballus), dog (Canis familiaris) and mouse (Mus musculus).
To view the alignments in further detail, click on the individual scores next to the hit.

NOVEMBER 2009


Breast Cancer
Diagnosis and Treatment Options
Stopping a deadly killer
Here’s a chilling thought: it is estimated that 1 in 8 women will be affected by breast cancer at some point during their adult life. It is the leading cause of cancer deaths among women. The global statistics are alarming, 7 million new cases are diagnosed every year, with nearly 1½ million women dying from the disease.
The link between mutations in genes and Breast cancer has been well documented.
The guilty gene
The best characterised gene in Breast cancer research is BRCA1. In normal cells this gene repairs mistakes in DNA. But when mutations arise in BRCA1, it loses its function. This is thought to trigger tumour formation.
A recent publication reported the use of a chemical inhibitor to selectively target BRCA1-deficient cells. DZNep (3-deazaneplanocin A) was used to inhibit the polycomb gene EZH2, which is known to be over-expressed in breast tumours. The success of the inhibitor indicates that EZH2 is a druggable target.
A design for hope
To measure expression levels of EZH2 in BRCA1-deficient human breast tumours and cell lines, a suitable probe has to be designed that is specific for the EZH2 gene.
SynaProbe is tailor-made to create such a probe. This on-line application designs and selects suitable oligomer probes for a gene of interest, in this case, EZH2. It is complemented by SynaHybridise, which verifies probe sequence specificity, to ensure that the risk of false positives is reduced as much as possible.
Both these applications can also be used for designing probes to detect and quantify other genes that are involved in Breast cancer such as Bmi-1, Ink4A and Ink4B.
To design a suitable probe, please follow the steps below:
Step 1 of 3
Click here, to submit your query.
Step 2 of 3
On the results page, click on to verify probe sequence specificity.

Step 3 of 3
The result demonstrates that the selected probe is specific, with only one possible binding site in the genome.

Read the full paper here: Breast Cancer Research 2009.

Prostate cancer is the most common type of cancer that affects human males. It is often asymptomatic and develops over a long period of time. Nearly 750,000 men are diagnosed with prostate cancer every year. Interestingly the incidence is highest in Scandinavia, Western Europe and North America, and lowest in South and East Asia. This suggests a strong genetic component to cancer susceptibility.

However, contrary to this finding, and in common with other cancers, a virus has recently been associated with the most severe forms of prostate cancer.

In September 2009, researchers from Utah discovered that the Xenotropic murine leukaemia virus (XMRV) was found in 27% of the 200 prostate cancer cases investigated. The virus seems to associate itself with the most aggressive tumours. This important discovery could lead to the production of a vaccine based upon an anti-viral antibody, as is the case with Cervical cancer and Human Papilloma Virus.

What is interesting is that the virus has an androgen response element and seems to grow better in the presence of testosterone. This could be a very important step towards understanding how the cancer is triggered and subsequently, how it can be controlled.

A major XMRV integration site has been mapped to a gene encoding a suppressor of androgen receptor transactivation (APPBP2). It can be hypothesised that upon XMRV infection, androgen receptor transactivation is increased by the blocking of APPBP2, which could be the trigger for cancer. Comparing the sequence of APPBP2 to XMRV using SynaCompare identifies two short domains which are highly homologous and could be the sites of insertion, leading to the disruption of the protein.

Step 1 of 3
Click here, then click on .
Step 2 of 3
On the results page, click on to view thick lines.
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Two short homologous domains can be seen.

Right click and move cursor to select region and click inside selected region to zoom in.

It can be hypothesized that these homologous regions could be the sites of insertion, leading to the disruption of the protein.
Source : BBC News.

Annotation of functional domains

Traditional herbal remedies offer great potential as alternative therapeutics for human diseases. However, most species that have shown promising results are poorly characterised in terms of active ingredients or mechanism of action.

An interesting recent discovery was that of a key component in lemongrass called citral, which prompts in vitro cancer cells to commit suicide via apoptosis. The mechanism by which apoptosis is induced by citral has not been fully characterised and there is little sequence information pertaining to citral production in lemongrass.

It is known that cinnamyl alcohol dehydrogenase is involved in the production of citral. We identified a protein for cinnamyl alcohol dehydrogenase from Ocimum basilicum (sweet basil) and used it to determine the locations of potential active regions/domains. We subsequently searched the Swissprot protein database to identify other potential plant candidates that contain similar functional regions/domains. This analysis could help increase the understanding of citral and how it may be used in the treatment of cancer.

An example of the usage of an online application in investigating cinnamyl alcohol dehydrogenase is shown below.

To annotate and search for similar proteins in other plants, please follow these steps:

Step 1 of 4
Click here, then click on .
Step 2 of 4

Select the entire region and left click within the selected region window.
Step 3 of 4

As can be seen from the Swissprot keywords, the SIGNIFICANCE peaks correspond to cinnamyl alcohol dehydrogenase. Again select the entire region of the graph as shown.

Right click within the selection and choose 'Synasearch sequence'.

Step 4 of 4

The region highlighted in blue is a potential genic region, and shows that cinnamyl alcohol dehydrogenase is quite conserved among selected plant species e.g. Medicago, Eucalyptus and Nicotiana (tobacco).

The sequences from these plants can then be further investigated to determine if they share the same capability of inducing cancer cell apoptosis.

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