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Posts from the ‘Gene’ Category

Wikis as Tools in Genetics

I’ve been planning to write about these wikis that can be very useful tools in the hands of researchers for a long time. The first one is WikiPathway which is an open platform dedicated to the curation of biological pathways by and for the scientific community.


The second is the WikiGenes which aims to build the database of evolutionary knowledge on


The reason why I mention the third one now is there is a new publication focusing on the pros and cons of using a wiki in genetics research. In Wikipedia, Andrew and his friends created the Gene Portal a year ago and later analyzed the usability and the results.

Annotating the function of all human genes is a critical, yet formidable, challenge. Current gene annotation efforts focus on centralized curation resources, but it is increasingly clear that this approach does not scale with the rapid growth of the biomedical literature. The Gene Wiki utilizes an alternative and complementary model based on the principle of community intelligence. Directly integrated within the online encyclopedia, Wikipedia, the goal of this effort is to build a gene-specific review article for every gene in the human genome, where each article is collaboratively written, continuously updated and community reviewed. Previously, we described the creation of Gene Wiki ‘stubs’ for approximately 9000 human genes. Here, we describe ongoing systematic improvements to these articles to increase their utility. Moreover, we retrospectively examine the community usage and improvement of the Gene Wiki, providing evidence of a critical mass of users and editors. Gene Wiki articles are freely accessible within the Wikipedia web site, and additional links and information are available at Wikipedia.

Potential new treatment for cystic fibrosis?

I just found an interesting article at the PHG Foundation about a new potential treatment for cystic fibrosis, a genetic condition affecting the exocrine (mucus) glands of the lungs, liver, pancreas, and intestines. It is caused by a mutation in the CFTR gene. The product of that gene is a a chloride ion channel that plays role in creating digestive juices and mucus. If there is no normal copy of the gene, the person will be affected by CF.

The new drug VX-770 was developed by the Cystic Fibrosis Foundation in collaboration with Vertex Pharmaceuticals; it targets the defective CFTR protein to improve chloride transport. The Cystic Fibrosis Trust supports a group at the University of Bristol in investigating how new drugs restore function to defective CFTR proteins; group leader Dr David Sheppard reported results at the BA Festival of Science indicating that the new drug could cause a near 50% reduction in salt levels in sweat and a 10% improvement in lung function in cystic fibrosis patients. He said: “The early results with VX-770 suggest that drug therapies which target defects at the root of the disease have the potential to improve greatly the quality of life of CF patients”

Here is a video describing the symptoms:

Gene Genie 34: Summertime

This is the first time I host Gene Genie since January. Gene Genie is the blog carnival of clinical genetics and personalized medicine. Enjoy the numerous posts and articles focusing on these interesting fields of medicine.


Many thanks to Ricardo Vidal for the logo!

Gene – Phenotype:

Walter Jessen at Highlight HEALTH had a great post, Neurofibromatosis: From Genes to Complications to Treatments.

On Science Blog, you can read more about women’s genes and alcoholism.

Daniel MacArthur at Genetic Future presented the adventure gene.

Steve Murphy, our Gene Sherpa, informed us about a new gene in atrial fibrillation.

Rebecca Taylor at Mary Meets Dolly talked about a lesson in genetic testing: the I148T mutation.

said Rett Syndrome was on Fox Show.

Yann Klimentidis analyzed some skin cancer and pigmentation genetic variants.

Chavonne Jones at Human Genetics Disorders posted an article and a video about Marfan Syndrome.

Genetic Testing:

Aaron Rowe at Wired listed 10 reasons why regulators should not hinder genetic testing.

The DNA Testing Blog talked about DNA testing for members of the military.

Personalized Medicine:

Jason Bobe at The Personal Genome shared the Wired article of Thomas Goetz with us.

Andrew Yates at Think Gene reviewed the deCODEme Genome Browser.

A Forum for Improving Drug Safety featured genetic influence in antidepressant effectiveness.

At Genetic Future, you can read more about the challenges of psychiatric genetics.

Yann Klimentidis analyzed structure-informative SNPs among European Americans.

Deepak Singh at BBGM said thinks your SNPs are your information.

The question at Genomeboy is to sink or to swim.

Dr. Eric Topol introduces the Genomic Medicine Resource Center with a discussion of personal genomics.

Wikis and Else:

Larry Moran at Sandwalk presented a Gene Wiki. Check the comments out as well.

According to Wired, Genes Don’t Explain African AIDS Epidemic.

Evolgen tried to help us answer the question, how many genes we share with our twentieth cousin.

The 35th issue of Gene Genie will be hosted on the 3rd of August. Don’t forget to submit your articles via the official page.

And also check the Gene Genie official blog out! If you’d like to host an edition, don’t hesitate to contact me at berci.mesko [at]

Gene2MeSH: Automated Literature Based Genome Annotation

Some weeks ago, I mentioned on Twitter how hard it is to find proper gene-disease associations in Pubmed, the database of health-science data. Some days later, P. F. Anderson sent me this link: Gene2MeSH.

According to her:

Gene2MeSH was described 2 me as mapping various terms used 2 describe the same gene, or genes assoc w/ medical term

I gave it a try and made a search for psoriasis:

It looks like an interesting and useful idea, while the MeSH heading column seems to be totally unnecessary, for example.

I will keep on using it and will let you know how it goes.

Further reading:

Personalized Medicine: Real Clinical Examples!

There are more than 60 articles in the personalized medicine category on my blog and I have a page dedicated to this emerging field of medicine. I also wrote a summary about it. But now it is time to show you some real examples; some cases and ideas that could play a major role in the future of healthcare. Genetic tests and pharmacogenetic variants which are used in clinical practice or will be used soon. I would like to consider this post as a continuously developing collection or database of examples and ideas. Please let me know if you know other examples of personalized medicine that were published in a peer-reviewed journal.


  • Azathioprine (AZA) and 6-mercaptopurine (6- MP) in inflammatory bowel disease¹:

Thiopurine S-methyltransferase (TPMT) is a key metabolic enzyme for azathioprine (AZA) and 6-mercaptopurine (6- MP), 2 widely used medications in the treatment of IBD. AZA is metabolized to 6-MP and subsequently 6-thioguanine (6-TG), the active metabolite. 6-MP can be inactivated by either TPMT or xanthine oxidase to nontoxic products. SNPs in the TPMT gene reduce TPMT activity, shunting metabolism to 6-TG and increasing toxicity, particularly neutropenia; TPMT deficiency can serve to lower the starting dose or to alternative therapies. TPMT enzyme (phenotype) activity in red blood cells and genotype testing to detect the major mutations that lower TPMT activity are both available and used by most physicians in the United Kingdom, including 75% of gastroenterologists. Approved by the US Food and Drug Administration (FDA), TPMT testing has led to relabeling for AZA and 6-MP to provide genomic information to providers.

  • Methotrexate in Crohn’s disease¹:

This pharmacogenetic test is used in IBD treatment. The SNPs of methylenetetrahydrofolate reductase (MTHFR) are associated with increased toxicity of methotrexate used to treat Crohn’s disease.

  • Her2/neu positivity in breast cancer²:

HER2/neu is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor.

Human epidermal growth factor receptor 2-overexpressing breast cancer is known to be associated with particularly aggressive disease and poor prognosis. On the other hand, human epidermal growth factor receptor 2/neu overexpression may predict response to endocrine therapy or chemotherapy. Nevertheless, trastuzumab increases the clinical benefit of first-line chemotherapy in patients with metastatic breast cancers that overexpress human epidermal growth factor receptor 2. In the pretrastuzumab era, retrospective analyses have shown that human epidermal growth factor receptor 2 overexpression is an adverse prognostic factor associated with an increased risk of disease recurrence and death. In the trastuzumab era, this drug has changed the natural history of human epidermal growth factor receptor 2-positive breast cancer, either in the metastatic or, according to the most recent evidences, in the adjuvant setting.

  • VKORC1 and CYP2C9 polymorphisms in warfarin metabolism³:

Warfarin is the most widely prescribed oral anticoagulant, but there is greater than 10-fold interindividual variability in the dose required to attain a therapeutic response. Pharmacogenetic analysis of two genes, the warfarin metabolic enzyme CYP2C9 and warfarin target enzyme, vitamin K epoxide reductase complex 1 VKORC1, confirmed their influence on warfarin maintenance dose. Possession of CYP2C9*2 or CYP2C9*3 variant alleles, which result in decreased enzyme activity, is associated with a significant decrease in the mean warfarin dose. Several single nucleotide polymorphisms (SNPs) in VKORC1 are associated with warfarin dose across the normal dose range. Haplotypes based on these SNPs explain a large fraction of the interindividual variation in warfarin dose, and VKORC1 has an approximately three-fold greater effect than CYP2C9. Algorithms incorporating genetic (CYP2C9 and VKORC1), demographic, and clinical factors to estimate the warfarin dosage, could potentially minimize the risk of over dose during warfarin induction.

FDA approved it last year.

  • CYP2C19 polymorphism in Helicobacter pylori–related disorders¹:

The treatment of H pylori infection requires a multidrug regimen that contains multiple antibiotics plus proton pump inhibitors (PPIs) or histamine-2 receptor blockers for eradication. Pharmacogenetic studies have revealed potentially important host genetic variability to PPI response; CYP2C19 SNPs define patients as rapid (RM), intermediate (IM), or poor metabolizers (PM). Asian populations demonstrate a higher frequency of PMs, higher PPI efficacy, and may have better H pylori eradication at standard doses. With omeprazole the most sensitive to CYP2C19 variation, H pylori eradication rates may vary with specific PPIs and are generally lower; higher PPI doses may be needed in RMs. Pretreatment PPI genotyping improves H pylori eradication rates but cost effectiveness has not yet been studied.

  • UGT1A1 polymorphism in irinotecan treatment of colon cancer¹:

Irinotecan, a topoisomerase I inhibitor, is a first-line treatment for colon cancer, alone or in combination. Delivered as a prodrug, irinotecan must be metabolized to SN-38, an active compound that is then inactivated by UDP glucuronosyltransferases (UGTs). Variability in one of these enzymes, UGT1A1, leads to accumulation of SN-38 and increased toxicity, most notably neutropenia and diarrhea. Specific UGT1A1*28 and UGT1A1*6 (in Asians) SNPs markedly increase irinotecan toxicity risk. Further, Gilbert’s syndrome, a benign disorder of indirect hyperbilirubinemia, is caused by the same mutations and predicts irinotecan toxicity. The FDAhas relabeled irinotecan and approved tests for UGT1A1*28 SNPs; UGT1A1*6 analysis will be additionally needed for Asian patients. UGT1A1 testing may prevent severe irinotecan toxicity through dose reduction or switching to an alternative oxaloplatin-based regimens. For oxaloplatin, genetic testing for SNPs in the DNA repair genes XRCC1, ERCC1, and ERCC2 and glutathione-S-transferase (GST), predict better response, although diagnostic tests for these mutations are not yet routinely available.

  • Polymorphism of 5-fluorouracil in the treatment of gastric cancer¹:

Even with the arrival of new biologic agents against colon cancer, 5-fluorouracil (5-FU) remains a mainstay of treatment but carries a high risk of adverse effects. Multiple SNPs in DPYD decrease DPY enzyme activity, which would normally inactivate 5-FU and its orally administered prodrug capecitabine; heterozygotes for these genetic variants reach a prevalence of 3%–5%. Cost effectiveness will determine the usefulness of DPD enzyme assays or genotype testing for DPYD variants prior to using 5-FU or capecitabine. In addition, genetic variants in the thymidylate synthase promoter lead to decreased tumor response to 5-FU–based regimens. Pharmacogenetic lessons learned in colon cancer treatment seem to apply to gastric cancer.


  1. Patel KK, Babyatsky MW. Medical Education: A Key Partner in Realizing Personalized Medicine in
    . Gastroenterology. 2008 Mar;134(3):656-61.
  2. Ferretti G, Felici A, Papaldo P, Fabi A, Cognetti F. HER2/neu role in breast cancer: from a prognostic foe to a predictive friend. Curr Opin Obstet Gynecol. 2007 Feb;19(1):56-62.
  3. Yin T, Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 – rationale and perspectives. Thromb Res. 2007;120(1):1-10. Epub 2006 Dec 11.

Personalized Genetics: Research in the News

When I started to share the most recent news and improvements of personalized genetics or genomic medicine, it wasn’t an easy job to find 4-5 articles a week. Now, my bookmark is totally full and I have to write posts focusing on different aspects of this special field of medicine. This time, while a whole genome sequencing costs less than 60,000$, genomic research should be in the focus:

Consumers also lack confidence and knowledge about genetic testing. They are generally concerned with privacy and the possibility of discrimination in health insurance and employment. However, consumers were interested in the genomic technology that can lead to better diagnosis and care for certain diseases – the ones for which they and their family members are at increased risk.

These genomic companies have taken a huge financial and clinical risk in bringing these tests to the market. The tests are in their infancy and each of these companies are transparent in advising their customers of this fact. That said, massive scientific research continues to take place to build on the knowledge base of these tests, so that they may be refined. This process will never end.


After gathering extensive experimental information on the metabolic networks of three different single-celled organisms, the researchers built a general quantitative model that can be used to control and restore biological function to cells impaired by a genetic defect or by other factors that compromise gene activity. Their network-based method does this by targeted deletion of genes, forcing the cell to either bypass the functions affected by the defective gene or to compensate for the lost function.

Demo Account at 23andMe: Analyze Your Demo Genes!

I thought I should create an account at 23andMe and see what happens with my demo genes. Of course, you cannot analyze your own genes (or you can, if you ordered their service), but the genetic background of the Mendel-family. I started with the Gene Journal where you can check whether you have elevated risk for some specific medical conditions.


It’s not so easy to tell you your exact risk, because even if some single nucleotide polymorphisms (SNP) in your genome indicate an elevated risk for heart disease for example, there might be some others SNPs we don’t know yet which lower your risk. So it’s really hard to give you a reliable result. That’s why it would be so important to talk with a geneticist about your genomic data. As your doctor won’t send you your lab results to analyze at home, your genomic data should be examined by a physician as well.

So here are the medical conditions they analyze (among others):


Research confidence is crucial. What does it mean?

Established Research topics meet 23andMe’s criteria for findings that are very likely to reflect real effects. The scientific community has largely reached consensus on these topics.

Generally, associations in these topics were discovered in studies of at least 1,000 cases and 1,000 controls and then replicated in a second, independent study of similar size. However, we may also include associations discovered in smaller studies if the scientific community has reached broad consensus that the effect is real.

You can browse your genome by body parts or organ systems if you wish:


Then I switched to Ancestry where you can explore your origins through DNA. In the Maternal Ancestry page, there is a map showing the locations of your haplogroup. What is a haplogroup? 23andMe has the answer:

Haplogroups are families of mitochondrial DNA types that all trace back to a single mutation at a specific place and time. Technically, every new mutation creates a new haplogroup, but geneticists only label the ones that help them trace significant events in human prehistory, such as the migration of people to the Americas or the expansion of agriculture from the Near East.


But my favourite tool is the Family Inheritance where you can browse among the genomes of the members of your family. Just compare your immune system compatibility to your sister’s or compare any set of genes.


After that, in the Genome Labs, make some genome-wide comparisons like this one in the Mendel family so you can find out how similar you are with your father or mother.


Then don’t forget to browse your own SNPs gene by gene.


At last, download your own data which would take about 5MB.

To sum it up, the whole site is colorful, these tools are easy to use, but after getting an e-mail about my genomic data and logging onto the site, I would like to talk with a geneticist because these results might lead to medical decisions and these decisions should be made by medical professionals and should be based on peer-reviewed data and evidence-based medicine, and not online tutorials.

Further reading:

Wikipedia: Reliable Sources and Gene Wiki

Wikipedia is a good first place to go to do your research, but should never be the last place to finish with!

We’ve got more than 2 million articles now so our only aim at this stage is to fill up the medical articles with proper references. For those who would like to know more about Wikipedia’s citation policy, check out this: WikiProject Medicine/Reliable sources.

Wikipedia’s medical articles, while not a source of medical advice, are nonetheless an important health information resource. Therefore, it is vital that medical articles be based on reliable published sources. These guidelines supplement the general guidelines at Wikipedia:Reliable sources with specific attention to sources appropriate for medical and health-related articles. The ideal source for such articles would be a general or systematic review in a reputable medical journal, or a widely recognised standard textbook written by experts in a field. It is also useful to reference seminal papers on the subject to document its history and provide context for the experts’ conclusions.


An other great project is the Gene Wiki presented by

The goal is to create gene stubs for every gene in the human genome. The stubs will have some minimal amount of structured content – links to important databases, GO annotations, PDB structures, etc. It’s our hope/expectation that these stubs will then seed contributions from experts in the field, specifically the “free-text” and unstructured sort of knowledge for which there really isn’t a great resource available.

If you’re interested, check out this link (warning – large page with long load time!) which lists the ~8000 (and counting) pages at Wikipedia that have incorporated structured content from our effort.

If you plan to contribute to this project, take a look at these categories and pages:

Further reading:

Gene Genie #23: Paradise of Genomics

Is it a paradise? You can decide after going through all the submitted articles. It’s my pleasure to host the newest edition of Gene Genie, the blog carnival of clinical genetics and personalized medicine.

Many thanks to Ricardo Vidal for the logo!

Let’s start with some clinical genetics-related news:

Terra Sigillata talks about the genetics of autism. Don’t forget to check out the comments as well!

Walter Jessen at Highlight Health focuses on the genetics of panic disorder.

I must agree with the opinion of Misha Angrist at Genomeboy: God forbid an Alzheimer’s diagnosis ever bums anyone out.

Elaine Warburton at Genetics and Health shares a new finding with us: Genetic manipulation ‘fixes’ Fragile X syndrome

I’m pretty optimistic as we can see some steps forward in clinical genetics.
We should move on now and focus on the genes!

Ramūnas Janavičius at Cancer-Genetics comes up with a series on breast cancer, the complexity of BRCA genes and COBRA.

Yann Klimentidis features ACTN3 which is an important gene for bodybuiders and powerlifters.

Sandra Porter at Discovering Biology in a Digital World hunts for huntingtin, the gene of Huntington disease.

BabyLab describes p53 & microRNA.


The next section is dedicated to the scientific and other aspects of human genetics:

Larry Moran at Sandwalk features the human genetic variation “Breakthrough”.

Flags and Lollipops dreams about a super-semantic-web-enabled phenotype database.

On Scienceroll, I provided some more tips on how to search for genetic conditions.

Jason Bobe at The Personal Genome is not too happy about the shortage of physician-geneticists in the United States.

And the friends of Simon Greenhill would use mtDNA to predict population size.


The last section belongs to my favourite topic, personalized medicine:

Lygeia Ricciardi at Project Healthdesign presents the Best Practices for Employers Offering PHRs.

Hsien-Hsien Lei at Eye on DNA shares the first personal genome results from 23andMe and deCODEme with us.

Corpus Callosum focuses on a really important subject: Genetic Testing for Antidepressant Medication Response.

Steve Murphy, the gene sherpa, says some words about his genetic company, Helix Health.

Deepak Singh at Business|Bytes|Gene|Molecules writes really deep-minded posts these days, the one I chose now is Your Personal Health: A little warning.

Blaine Bettinger at The Genetic Genealogist points out an interesting service, myDNAchoice – Are Your Surfing Habits the Result of Your Genome?

If you are a regular reader of Scienceroll and have seen some of my past editions, you know what is coming next. Yes, the finish with a funny genetics-related video, a rap about chromosomal mutations:

The 24th issue of Gene Genie will be hosted by Biomarker-driven mental health 2.0 on the 20th of January. Don’t forget to submit your articles via the official page.

And also check out the Gene Genie official blog! If you’d like to host an edition, don’t hesitate to contact me at berci.mesko [at]

Steps Forward in Clinical Genetics

As I promised I’m here again to keep you up-to-date about the wonderful realm of clinical genetics. While there is a shortage of geneticists in the US and in other parts of the world as well, we can see some improvements regarding certain medical conditions. Let’s start with fragile X syndrome.

Fragile X syndrome is the most common cause of mental retardation. As Wikipedia says:

Mutation of the FMR1 gene leads to the transcriptional silencing of the fragile X-mental retardation protein, FMRP. In normal individuals, FMRP binds and facilitates the translation of a number of essential neuronal RNAs. In fragile X patients, however, these RNAs are not translated into proteins.

Original source: Wikimedia Commons under Free Art License

The researchers of the Picower Institute for Learning and Memory at MIT have reversed symptoms of mental retardation and autism in mice. The FMRP protein binds to the mGR5 receptor on the surface of brain cells. A drug that inhibits the receptor may be useful in treating young Fragile X patients in the future. Check out the great report of Kristina Chew at AutismVox.

Second, FDA approved Kuvan for treatment of phenylketonuria (PKU), an other main cause of mental retardation.

Kuvan works by increasing phenylalanine hydroxylase enzyme activity in PKU patients with some residual PAH enzyme function. This then leads to an increased breakdown (metabolism) of phenylalanine (Phe), resulting in lower levels of Phe in the blood.

And last, but far not least, here is a fantastic article about mutations in breast cancer at Open Medicine. Kelly A Metcalfe and Steven A Narod present a common case and tell us how to help the patients with specific and accurate information or risk. Some weeks ago, Ramunas at Cancer-Genetics shared BOADICEA, a breast and ovarian cancer risk/mutation probability calculation web-application, with us.


And Hsien-Hsien Lei at Eye on DNA presented Opaldia, a genetic testing company that will offer the Diagenic breast cancer blood test in 2008.

The test detects gene expression patterns in peripheral (circulating) blood and is touted as being able to diagnose asymptomatic breast cancer before it can be detected by manual breast exam or mammograms.

Aren’t these announcements fantastic? Or am I too optimistic?


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