Category Archives: Genetics

Genetics

Pharmacogenetic tests on the market

Certainly one of the best web resources for pharmacogenetics is the PharmGkB database that collects all kind of data about the relationships among drugs, diseases and genes. Of course you could sequence your genome or run expression profiling on a liver sample. However, you are probably here to find out what (serious!?) pharmacogenetic tests are already on the market.

Much can be said about the usefulness of such tests; I have doubts if there will ever be such personalized treatment as I can foresee some logistic problems to validate it ;-) More likely are group based therapies, maybe restricted to geographic ancestry. Here is a (first and very) preliminary collection of commercially available pharmacogenetic tests:

  • CYP2D6, CYP2C9 and CYP2C19 collectively account for about 40 percent of drug metabolism mediated by cytochrome P-450 (Roche). The AmpliChip CYP450 Test is the world’s first pharmacogenetic microarray-based test approved for clinical use. CYP2D6 metabolizes codeine into morphine. A variation in CYP2D6 varies with race and leads to a lower elimination rate of the antidepressants Prozac (a selective serotonin reuptake inhibitors); the alternatively used drug Celexa is metabolized by CYP2C19 (as well as omeprazole). Other examples include clopidogrel (metabolized by CYP3A4) and cyclophosphamide (by CYP2B6) and vitamin K (by CYP2C9)
  • NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A carriers are rapid and slow acetylators for example of isoniazid or procainamide (Roche)
  • HER2+ women may get herceptin (Roche, Bayer, PathVysion)
  • TP, DPD are the rate limiting catabolic enzymes of 5-fluorouracil metabolism (Roche)
  • Mitochondrial A155G variants are tested for aminogylcoside side effect (Humatrix)
  • A Warfarin sensitivity test will be in clinical use next year (Kimball Genetics). It will test for variations in CYP2C9 and VKORC1
  • An UGT1A1 gene variant is associated with leukopenia if prescribed camptosar, a drug for colon cancer (Oncoscreen)
  • A TPMT variant is associated with slow metabolism of 6-mercaptopurine, used in the treatment of childhood leukemia and inflammatory bowel diseases (Pharmaco-Gendia)
  • Epigenomics is currently developing tests based on DNA methylation
  • Tyrosine kinase inhibitor gleevec inhibits the ABL, ARG, SCF/KIT, and PDGFRA and PDGFRB kinases in CML. Mutations in ABL can arise as secondary mutations in previously sensitive leukemias (Pharmaco-Gendia)

Needless to say that I have excluded here specific HIV mutations that may induce resistance to particular drugs (as I learned last week on a bioinformatics meeting here by Thomas Lengauer). I have also excluded all kind of sex-specific marker (e.g. SRY testing) and the whole nutrigenomics stuff.

Who knows more, for example about lansoprazole effectiveness, UGT1A9 and mycophenolic acid, UGT1A1 and irinotecan, COMT genotype and amphetamine response, pharmacogenetics of COX-2 inhibitors, and GRP78 responsiveness to chemotherapy? Is there any commercial test available for these genes? It seems that somebody should start a wiki on that, yea, yea.

Addendum 31-12-09

Here is another gene list; only 6 tests have been approved by the FDA; Nature reports about Oncotype DX and Prostate Px as well as MammaPrint. See also an UK based paper

HLA-B*5701 was most commonly tested to identify those at risk of abacavir hypersensitivity among patients with HIV. A number of barriers to testing were identified, including lack of clinician knowledge and a lack of scientific evidence.

 

CC-BY-NC Science Surf accessed 20.12.2025
Allergy, Genetics

INDELligent

I am detailing in a forthcoming paper in “Allergy”, that the contradicting results found with ADAM33 (the first positionally cloned asthma gene) probably results from a rather poor design of all follow-up studies.
It does not make so much sense to repeat over and over the same few SNP marker; instead a full resquencing of the linkage region would be necessary. From the analysis of public LD maps it is even possible that neighboring genes may be responsible for the observed associations.
I have also doubts if the SNP-centric view is always leading to success. BTW there is a new database of over 400,000 non-reduandt indels of which 280,000 are validated by comparison with other human or chimpanzee genomes (see Mills et al., the indels are available in dbSNP under the “Devine_lab” handle).

 

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Genetics

Best of two worlds

Finally, linkage and association data can be used together after downloading new software using genotype inference.

It reduces the number of genotyping reactions and increases the power of genome-wide association studies. Our method combines sparse marker data from a linkage scan and high-resolution SNP genotypes for several individuals to infer genotypes for related individuals.

Sure, we

Genetics

Geo IP identification

The Geo IP database is available at Maxmind and allows to trace your home city from IP addresses. Here is a quick and dirty script to upload the Geo IP data into MySQL:

|wj_geo.cmd|

I would also put an index on loc_id. Finally the database should be available as

SELECT city
FROM GeoLiteCity INNER JOIN GeoLiteCityBlocks ON GeoLiteCity.locID = GeoLiteCityBlocks.locID
WHERE $myIP >= startIpNum AND $myIP <= endIpNum;

where $myIP is calculated as

substr($_SERVER['REMOTE_ADDR'],0,3) * 16777216 +
substr($_SERVER['REMOTE_ADDR'],4,3) * 65536 +
substr($_SERVER['REMOTE_ADDR'],8,3) * 256 +
substr($_SERVER['REMOTE_ADDR'],12,3)

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics

A low-cost system for a PDF literature archiv I

Getting a scientific paper on your harddisk is quite simple. I am using a Fujitsu Scan Snap that can process a single page in a few seconds. The resulting PDF needs to be further tweaked by OCR recognition like ABBY FineReader (I couldn’t find any good open source alternative). FR will leave your PDF intact while adding recognized text as an overlay (or “underlay”). Unfortunately FR does not support batch processing but your OS will do by using a windows scripting engine like CLRscript. We also need a tool to extract a text file from the modified PDF. A good choice is pdftotext — look at the sourcecode and the DRM discussion before compiling it with a compiler like Cygwin. The following perl script doesn´t do anything than traversing your target directory and creating a batch file. As filenames offered by publishers are rather strange, I would first start to create some clean file names by replacing all spaces and brackets with something innocent like underscores.
perl.exe ocr.pl rename h:\pdf\2008\*.*
Now we create text files from the PDFs (usually done better by XPDF than directly by GDS).
perl.exe ocr.pl extract h:\pdf\2008\*.pdf
The resulting textfiles may be inspected: very small file sizes usually indicate no valid extraction and should be deleted before starting the OCR step as OCR is only done when text files are missing.
perl.exe ocr.pl ocr h:\pdf\2008\*.pdf
In the last step you may want to repeat the extract step.

ocr.zip
|wj_ocr.txt|

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics

Some are hybrids, some are not

Microchimerism is an interesting phenomenon that describes the hosting of foreign cells in an individuum – the prefix micro relates to the rather low counts of foreign cells (see the self discussion).
It is believed (but unproven) that most cases of microchimerism relate to the persistence of fetal cells in the maternal organism. The background of microchimerism is extremely complicated as highlighted in a recent review about the immunology of placentation in mammals. This paper has some nice cartoons about the types of placentation (epitheliochorial, endothelichorial and haemochorial) where the invasive potential of fetal trophoblast cells is the culprit of reciprocal (?) cell traffic between mother and fetus. The highest risk is found in women with induced abortion; cell count is ranging from 0 to 21 male cells per 100,000 female cells in peripheral blood; transfer may occur from mother <-> child, twin <-> twin, or sib <-> mother <-> sib.
Microchimerism has been examined in transplantation medicine (where the recipient replaces the outer donor organ epithelium), in blood transfusion and HCT, as well as in some autoimmune diseases (systemic sclerosis, SLE, thyroiditis, PBC). A clinical review reports that fetal cells have been found to persist for many years, probably for a lifetime.
I have doubts if that is true as I am not aware of any quantitative long-term study. Nearly all studies identified only male cells in women although now genomic studies of single cells are possible allowing a much better identification of foreign cells. If you are looking for a PhD thesis, microchimerism could be your field!
I already wondered if microchimerism could lead to genotyping errors, a question that can now easily be tested on the garbage of genotyping labs: We usually have genotyping errors in the 1-10 o/oo range; sometimes we see also triallelic SNPs. As far as I can renember, microchimerism has never been analyzed in the allergy field, although allergy can transplanted as well as asthma. Yea, yea.

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics

Are genes becoming more important with increasing age?

I found an apparent paradox between two studies. John Whitfield did a twin study in Australia and concluded that shared environmental effects decreased with age (from about 50% to 10%) while additive genetic effects increased. The new Sardinian study found higher heritabilities among younger individuals and explained that by an increase of environmental insults with age. Nice said, but who is right?

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics

WordPress as CMS

I have read many useful (and also some less useful) comments how to squeeze WordPress to work as a CMS.

I did not want to make any major changes to scripts that would be lost after an upgrade. I did not want to have extra plugins to change home (for example by creating an overriding home.cfm). I did not want to have any new categories. I did not want to change permalink structure. I still need my directory plugin to work, I still need the blog (some redirects even loose the blog address!) and I wanted to keep the RSS feed.

After several hours I came up with an very simple solution: Take a standard page and rename its title and slug to “Home” – assign a special “Home” template – redirect htaccess to this page. The only trick is to make the “Home” template work: it is basically a copy of the index.cfm in your WordPress theme directory where the line calling loop.php is being replaced with a slightly modifed loop code.

myblog.php
|wj_myblog.php|

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics

HUGO Changing Offensive Gene Names

Hsien Hsien Lei has a good comment on gene names approved by Human Genome Organisation (HUGO) Gene Nomenclature Committee which are nevertheless offending . Some of the inappropriate names are LFNG – lunatic fringe homolog (Drosophila), MFNG manic fringe homolog (Drosophila) as well as SHH sonic hedgehog homolog (Drosophila). There are many more names that arise only from a particular culture (like death executioner Bcl-2); it seems also a particular kind of humour to call a deaf mouse Beethoven. Yea, yea.

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics

Why we should believe professional cyclists

I renember a nice meeting in South Sardinia in 2002 (see my figure below) where a lot of famous people gathered for interesting talks in a wonderful surrounding.
A spin off from this Ogliastra Genetics Park – as the authors called it – is now a paper in PLOS Genetics that examines the heritability of 98 quantitative cardiovascular traits in 6,148 Sardinians.
Although the authors did not measure hematocrit, RBC related counts had an extremely high heritability (MCV 0.76, MCH 0.78). Hemoglobin was somewhat lower (0.47) which might in part be attributable due to some local selection factors. This result comes largely unexpected, as the high heritability of the MCV was not known so far.
In the absence of any assay for exogeneous EPO, hematocrit is used as an indirect parameter for testing athletes. I already wondered why cyclists are having such high values (if we exclude illegal drug use). This seems to be a genetically trait by self-selection – an anemic cyclist will not participate in the Tour de France. Yea, yea.

123-2325_img.JPG

Addendum

Here is an answer to the question what makes a champion ;-)

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics, Philosophy

On the “Self”

If I would ever find the time, I would write a book on the “self”. Inspired by the Eccles/Popper book that I bought as a student, I always wondered how different the self is being defined in sociology, psychology/psychiatry, philosophy and theology.
As my current focus is more on genetics and immunology, I found a paper by Francisco Borrego on the “missing self” quite interesting as it highlights the genetic self is determined mainly by MHC class I molecules, where only NK cells transfected with H-2Dd were able to confer resistance for being self-attacked. It would be nice if other disciplines could also provide such simple answers, yea, yea.

Addendum

I have another suggestion: Zfp608 protects mouse mothers against immune-mediated attack by fetal cells.

Is there also a “digiself“?

Our identity has, for many years, existed quite independent of our physical incarnation in government, financial and other institutional databases. We are not real to the bank or other authorities unless we can produce something that links our physical self to our “real identity” in their database. We have many versions of this digital identity – or digiSelf, as I like to call it – spread among many databases, each with its unique characteristics, and inferred behaviours. Each one is more real to the institution – and ironically, to the people in that institution – than our physical self, what we consider to be our real self.

 

CC-BY-NC Science Surf accessed 20.12.2025
Genetics

Don´t leave orphan links

Tim Berner Lee argued in his article “Cool URLs don´t change” to set always a server redirect if you have moved a page.
The frequently seen page reload using the header tags <META HTTP-EQUIV=REFRESH CONTENT="0;URL=http://new.server.de/tips_tricks/">
 is only suboptimal as spider will not follow them. Put instead one of the following lines in your your Apache con/http.conf or into the .htaccess file of your directory.

.htaccess
|wj_htaccess.txt|


Preventing bots from increasing your server load is another suggestion.

 

CC-BY-NC Science Surf accessed 20.12.2025