Tag Archives: Genetics + Biology

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.

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.

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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Systems biology

A nature genetics paper shows that a single mutation in Pseudomonas has pleiotropic effects – not limited to the level of proteins in the particular network but changing also their relationships. Sounds like a soccer match where a player has to leave  the court – which changes positions of all remaining players. “The adaptive mutation draws proteins into tighter coregulation”, yea, yea.

Bereshit bara Elohim et hashamayim ve’et ha’arets…

The genesis – the common book of Jewish and Christian faith – reports the begining of the world. Interestingly , the creation of living things include also genes in the same instance: “1.11 let the earth spawn grass and leaves that make seeds…” We have been told that reverse genetics may not be used any more. Whats about forward genetics? Yea, yea.

Munich, Pettenkofer, Nazis and Public Health: An obligation

Reading the biography of Max Pettenkofer you will discover unexpected turns (starting his career as a third class actor in Augsburg) but also recognize him as one of the founders of Public Health (with a big impact on Munich city development by canalization and foundation of a fire department). Munich had been on the forefront even before the foundation of the famous Boston Public Health school.

With Volksgesundheit the idea of Public Health became perverted by the Nazis. With Erbgesundheit in mind the Nazis even tried to eradicate genes from the gene pool. Munich became Hauptstadt der Bewegung, and its university even awarded Mengele (the later physician in Auschwitz) a PhD degree.

During post-war period there was probably no epidemiological research in Munich, with Public Health only an unimportant discipline in the medical curriculum. When doing a first major epidemiological study in Munich at the end of the 1980ies and a first genetic population based study in the mid 1990ies, I felt a particular obligation for informed consent where any misuse of genetic data should be avoided.

Unfortunately, these goals are being threadened by an increasing ignorance of informed consent and missing legislative framework for genetic testing in Germany.

10 commandments

  1. There is only one human genome.
  2. You should not misuse it for any other purpose than continuing human lineage
  3. Observe the order of exons and introns and nongenic sequences.
  4. Recognize recombination and preserve it for a long lifespan.
  5. Do not knockout genes.
  6. Do not mix genomes.
  7. Do not steal sequences from other genomes.
  8. Do not assign wrong functions to genes.
  9. Do not use chromosomes in other cells.
  10. Do not be jealous on your neighbours sequence nor on your neighbors wife sequence nor on your neigbours children sequence.

Yea, yea.

Siddur, mantra, prayer

The Jewish siddur, the Buddist mantra and Christian prayer all contain repeating elements. Why does our genome also has has so many long and short interdispersed repeats – to give life a stable background on an ever changing environment? Yea, yea.

SQL injection and retrovirus infection

What is similiar to SQL injection (in webforms) and retrovirus infection (of mammals)? I think there is always a vulnerable situation (tainted variable by unexpected data entry – or double strand break and ligation) that allows foreign code to be inserted. What is different? Retrovirus insertion is probably position specific while SQL injection can even determine its own target. Yea, yea.

Reading behind the lines

-moblog– Eran Segal et al. describe in Nature a genomic code for correct nucleosome attachment of genomic DNA. DNA must be positioned for access to functional sites of gene activity where 147 bases are wrapped around each nucleosome core. AT is favored where phosphodiesterase backbones face inward and GC where it faces outward. Distance between nucleosomes may be variable – as the accompanying editoral by Timothy Richmond explains (the enigmatic histone H1 question). Do genomes use nucleosome DNA preference to target transcription factor towards appropriate sites? This might expain why current transcription factor models are rather poor as they are using only sequence binding matrices. It reminds me to steganograpy, algorithmic procedures that can be used to hide secret messages in in pictures without affecting the visual impression. Yea, yea.

See no evil, hear no evil, …

See no evil, hear no evil, do not evil: The lessons of immune privilege” is the title of an excellent paper by Jerry Niederkorn in nature immunology. He basically says that there are only 3 human organs that allow foreign tissue grafts: eye, brain and pregnant uterus. If we leave the special situation of the uterus aside, and see the yes as an extension of the brain – there is only the brain that is no attcked by the immune self. Being still under influence of the Popper/Eccles discussion of the brain and its self , here is my back on the envelope picture of social self < -> immune self < -> conscious mind. Yea, yea.

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