A zebra takes its stripes wherever it goes

This week ends with another African proverb and some thoughts on transcription factor binding sites.

Commenting on the work of Janssens that “there is no inherent reason that CRMs [cis regulatory modules] must lie on a contiguous segment of DNA or that they must contain clusters of sites”, Halfon still expresses the hope that “we should be able to identify the regulatory elements for any gene starting with only the DNA sequence”.

Although an old dream, I am now rather sceptical if this prediction will ever work. Recognize the differences of my drawing compared to original figure: I am introducing even another level of temporal relationships. There might be even a close relationship to yesterdays post on “retaliation“, yea, yea.

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Do not run after a cart that will not take you

Starting with another African proverb, here are some thoughts about evolution, design and the difference of chimps and humans. Yes, I am biased, I know.

I have learned that there are mainly three differences between chimps and human – the ability to run, a larger brain size and the language/speech capability. The only trait that can directly observed is the ability to run (check Munich marathon: Neither brain size and language can be directly observed :-) BTW, I renember having seen a family that walk on feet and hands – quadrupedal locomotion is a recessive trait linked to chromosome 17p, the way we all start our lifes).

So genetics is playing a big role in the human < -> ape differentiation. Or did the differentation select the genes?

You will understand my great expectations when now reading one of the first serious papers about the chimp and the human lineage. It is about pseudogenization, the gene loss during separation of species. The authors show 80 non-processed pseudogenes inactivated in the human lineage – while gently negelecting the fact of another 7868 or so pseudogenes in the human pseudogene database.

There is also nothing about my favorite trait bipedalism (only a ridiculous quote of pseudogenization of the sarcomeric myosin gene MYH16 that should relate to hominin masticatory muscles that “may have allowed the brain size expansion”, uhhh. It is also hard to understand how gain of ability should be caused by loss of gene function, yea, yea.

Dr. Livingstone, I presume?

Asthma in Africa: I will touch this issue in more detail in a forthcoming editorial in PLos Medicine. Africa has fascinated me since childhood when I read books of Paul White, Albert Schweitzer and tried to get everything our library had about David Livingstone and Morton Stanley. Here is a further link that we couldn’t place in the editorial – a 2 month helicopter trip from Hamburg to Kapstadt including daily GPS data to watch a heli flying in Google Earth, simply the best, I have seen in the internet this year, yea.

And the winner is…

Don´t miss the Ig Noble Ceremony. For example:

  • Why woodpeckers don’t get headaches
  • An electromechanical teenager repellant
  • Calculating the number of photographs you must take to (almost) ensure
    that nobody in a group photo will have their eyes closed
  • Consequences of erudite vernacular utilized irrespective of necessity:
    problems with using long words needlessly
  • Termination of intractable hiccups with digital rectal massage

yea, yea.

Are randomized clinical trials gold standard?

A new paper in the Deutsche Ärzteblatt argues that there should be alternatives to RCTs. The reasons are manifold

  • selection bias towards more severely ill patients
  • selection towards too homogeneous samples
  • patients may decline participation
  • physician may decline participation
  • bias towards larger cities and universities
  • usually “hard” endpoints that ignore quality of life, compliance, side effects
  • usually only short time studies
  • protocol may deviate from daily practice in medical routine

Community-based studies may therefore not be as bad, yea, yea.

Addendum

An extended and reworked version of this blog can be found in issue 45 of the “Deutsche Ärzteblatt“, page A3019, 10th November 2006.

Genetic archaeology

While doing a study of European population stratification, I came across an older but interesting study of old testament priests that compares the Levi tribe (where Moses was a member) with the Cohanim tribe (descendents of Moses’s brother Aaron who served as priests). The investigators traced patrilineal inheritance since the temple period 3,000 -2,000 years until present, and showed current levites unlike the Cohanin having a heterogeneous origin. The coalescence of of Cohanim chromosomes is dated to between Exodus and the destruction of the first temple in 586 BC.

Most current research is dedicated to between species comparisons but unfortunately the wonderful older Y and mtDNA approaches haven´t kept pace with the current SNP technology developement. There would be many intersting studies possible following the timeline of European history, yea, yea.

Beauty is skin deep but ugly goes all the way to the bones

Sorry, the original title of this paper is “Nothing but skin and bone“. It is an excellent JCI review of two diverse systems that do not seem to have so many common denominators. As the authors state a recurring theme is Wnt (a family of secreted glycoproteins) signalling during early patterning and for morphogenesis of skin appendages – common mesenchymal progenitors support both tissues. What the authors neglected is the effect of vitamin D signal in skin and bone, yea, yea.

Genomics of a single cell

This is a fascinating area – methods for amplifying DNA from single cells for complete genome sequencing. The current approach uses isothermal multiple displacement amplification MDA, followed by 454 sequencing. Biotechnology is getting closer towards its origins, yea, yea.

Addendum

We can now add also single cell protein analysis – microfluidic devices that can dissolve and separate proteins before quantifying them by fluorescence in confocal microscopy. Several groups tried to increase the signal-noise ratio by decreasing capillary dimension (leading to clogging) while the new study widens the excitation laser.

Towards a framework of SNP interaction

The forthcoming SNP whole genome association studies will draw a lot of attention. I already have the problem of many interacting SNPs where I am suggesting to divide significant results in 3 compartments – local (LD effects), longrange (cis transcription factor effects) and pathway effects (gene family, system wide effects). The main problem are false positives that can even not be overcome by techniques like FDR. Yea, yea.

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