Allelic specific expression

This topic has fascinated me since I read the Pastinen paper from the Hudson group (with updates in Science and Hum Mol Gen; the field probably started with the Yan paper). We had even written a DFG grant application that was not funded.

ASE uses a rather simple principle where the allelic ratio of a heterocygous SNP within a RNA transcript is taken as a measure of gene expression from the different chromosomes (that are carrying either the one or the other SNP allele). A ratio of 0.5 indicates equal expression and becomes distorted if a gene on one chromosome is imprinted or silenced by another way. The ratio can be rather easily determined by MALDI-TOF genotyping of cDNA by pooling protocols. I wonder why this hasn´t been more used as it is probably a more precise measurement than the artificially “self-normalized” expression ratios in classical gene-expression profiling (as Fan pointed out recently).

ASE seems to be much more common than I thought: 53% of all genes showed allele expression differences in at least one individual. Having such a screening instrument at hand, it could even help to clear our SNP genotyping lists. Yea, yea.

Another difference between men and women

Aside from sex hormones, circulating vitamin D – calcidiol – serum levels show a consistent difference between men and women. Ok – I know that

  1. nuclear receptors are hormone-dependent transcription factors (Drané P, Mol Cell 2004; 16:187)
  2. 25-OH-D3 hydroxylase is upregulated by estradiol-17 (forgot reference)
  3. endometrium expresses VDR during cycling (Vigano, J Mol Endo 2006; 36:415)

but what is really responsible for this difference? A new Cell paper now shows that tamoxifen (an estrogen receptor antagonist) disrupts calcium homeostasis in yeast. Yea, yea.


Don´t read this if you haven´t finished your thesis.

Tadataka Yamada -former chairman of research and development for SmithKline Beecham Pharamaceuticals- is quoted in The Lancet of August 12, 2006, that “99% of what we do in industry fails”.

John Ioannides revises his PLOS statement from “most” research finding is false to “up to 90%” for a moderate risk factors with limited replication. Given the fact that many negative studies are never published, also academia would be in the Yamada range.

I should have been taught that earlier. Yea, yea.

Geneticists and NBIA-PKAN

Geneticists continue to publish about “Hallervorden-Spatz” or “former Hallervorden-Spatz” syndrome.

The German NBIA patient group advocates for many years that these names should be abandoned (the American patient group even formally changed its name 2003). NBIA is a rare inherited neurological movement disorder characterized by the progressive degeneration of the nervous system; NBIA means “neurodegeneration with brain iron accumulation”. Another frequently used disease synonym is pantothenate kinase-associated neurodegeneration (PKAN).

The clinical syndrome has been described by the neurologist Julius Hallervorden and the neuropathologist Hugo Spatz. Robert Jay Lifton does not h>ave any material about Hallervorden and Spatz in “The Nazi Doctors: Medical Killing and the Psychology of Genocide but Ernst Klee in “Auschwitz, die NS-Medizin und ihre Opfer” and Benno Müller-Hill in “Murderous science” mentions both. Professor Hugo Spatz (1888-1969) was docent in Munich 1923, director of Kaiser-Wilhelm-Institut Berlin 1937-1945 and director of Max-Planck-Institut für Hirnforschung Gießen 1948-1957. Professor Julius Hallervorden (1882-1965) was department head at Kaiser-Wilhelm-Institut Berlin 1938-1945 and at MPI for Brain Research from 1948 on.

The former director of Max-Planck association Professor Hubertus Markl mentioned their involvement in Nazi euthanasia in his lecture on Oct 14, 2000 at MDC in Berlin-Buch (own translation): “Recent research showed that brains of hundreds of euthasia victims killed between 1939 and 1944 in Brandenburg-Görden, were mis-used for research purposes. In a single case Julius Hallervorden was present in person, while children were killed in Görden and brains consecutively analysed in his laboratory… As a biologist it remains for me to declare that this is an eternal dishonor for German bioscience.”

The sib similiarity problem

We have done affected sib pair studies for many years with moderate success as we already described five years ago. Professor John Edwards brought to my attention the “sib similiarity problem“, that is still not widely known. ASP studies are based on “the premise that a set of ASPs will share more than the expected proportion of alleles at a disease-susceptibility locus with the implication that these were the sole cause for excess sharing”. This is not necessarily true and may be one reason of the failure of ASP studies. More or less by chance, I found that that the observation of 1 discordant sib in ASP families be an extremely powerful. “Being sane in an insane world” e.g. being healthy while having most of the risk alleles and all the environment risk that made the sibs ill. Yea, yea.

Who is who in German genetic research?

You may want to start with names listed at Laborjournal. Aside from universities major institutes are with Max Planck and Helmholtz. Main funding comes by DFG (Deutsche Forschungsgemeinschaft, who lists all their projects at GEPRIS) and by BMBF (German Ministry of Research) with a few projects online at National Genome Research Network.

More about parents and self

I would be interested to learn more about the rate of non-matching parent-child SNP assays (preferably Affymetrix technology as current Illumina chips do not include low MAF variants).

This could tell us something about the role of de novo somatic mutations: Read more in a recent TIGS paper by Kenneth Weiss. Has anyone checked different tissues of the same individual and looked for mosaics? Or traced the fate of blood transfusions? Or followed up a single individuals over a couple of years?

This idea is also fuelled by a recent Cell paper that shows Sticker’s sarcoma to be transmitted among dogs by licking or biting tumor-affected areas. Yea, yea.

Pater emon o en tois ouranois – About paternity testing

The Lord’s prayer has been translated into nearly all languages (where 1,377 languages are online). Having a father in heaven is comforting but from a genetic standpoint we don´t take it literally (in contrast to some other family relationships in the Lutheran tradition).

Although pedigrees usually list only father names, the absolute amount of DNA transmitted from father to children is less than for women, who always transmit a long X as well as mitochondrial DNA. When testing for paternity in family studies, my experience is that about 3% of the children do not match with their fathers (while I have never found a mother that did not match). This fact does not seem to be new: Already the Romans knew that “Mater certa, pater semper incertus“.

Is DNA testing for paternity really so important as many commercial websites make you to believe? Genes are part of our existence, environment is another as well as what WE want to achieve in life. Nay, nay, genes are not so important knowing so many wonderful non-genetic fathers.

From misunderstanding to dogma

The Nature Reviews Genetics Timeline features an interesting story on human chromosome numbers. Theophilus Painter in his 1921 Science paper wrote: “In my own materials the counts range from 45 to 48 apparent chromosomes” which was interpreted for obvious reasons to be 46 or 48 (Painter probably saw a bended chr1 as 2 different ones). Textbooks then reported 48 human chromosomes for 3 decades until the classical paper of Tijo in 1956 paper who confirmed 46 human chromosomes. Gartler believes that Tijos unusal background have made him likely to question authority. Yea, yea.

What’s in a name?

What’s in a name? That which we call a rose. By any other word would smell as sweet. From Romeo and Juliet (II, ii, 1-2).

Geographical distribution of names may indicate spreading of gene variants – a fact that has been ignored so far in genetic research. If you are interested in European names, here are some interesting links. It is now even possible to draw your name on a map – on the fly. Yea, yea.

Here is map of my name (yes, a couple of errors, but the locations are close to what I have found in our 70 year old family register).




Not invited to Lindau?

Lindau at Lake Constance hosts the annual Nobel laureate meeting. In addition some 500 young students from all over the world can listen to the Laureates’ lectures and to engage in discussions with them. Not invited? There are some excellent interviews available (for 2003-2005 but we are all waiting for 2006).

Interested in the history of DNA discovery? There is a wonderful Linus Pauling website that has it all: A wealth of primary sources – over three hundred letters, manuscripts, photographs, published papers, audio-visual snippets and more – provide an important scholarly perspective on the DNA story. Yea, yea.


Ever failed with a grant application? Sad? Don´t worry, submit your grant somewhere else.

This will, however not work in Bornemouth. As the local newspaper says: “A new telephone system has been launched in Bournemouth town centre that aims to stop troublemakers from getting into bars, clubs and pubs. Doorlink enables doorstaff to take pictures of any problem drinkers via their mobile phones and within seconds circulate them to other venues in a bid to stamp out violent behaviour.” Yea, yea.


If you are invited to a party just mention genetically modified (GM) food and you will be center of the crowd. There are many national and internationally bodies that deal with GM food (see the dissertation of Scholderer). As far as we do not know what makes and allergen and allergen, I would always care when introducing any modification. There is a way round, however, that GM food can also have less allergen content – just found a preprint of a gene-silenced tomato. This German-Spanish group managed by RNAi silencing to reduce protein Lyc e 3 with led to reduced skin reactivity of tomato allergic probands. BTW – do you renember our fake food hypothesis? Yea, yea. BTW The best tomato bread can be found in Barcelona.