Category Archives: Genetics

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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Magic tooth

David Wang from the school of Dentistry of UCLA makes an astonishing claim in a company interview about the 1.5 l saliva that we produce every day: “…Real-time changes in our body could be monitored by having sensors to sense changes … implant a tooth with a sensor … that comes into the astronaut’s oral cavity…”. Even genomic and proteomic analytes are possible if we think of recent lab on a chip developments. Yea, yea.

Pushing the limits of cytogenetic FISH

-moblog- HMG has an interesting paper of Fei Sun and Renee H. Martin – showing a first visable recombination map of the male human genome. They obtained testicular samples from 10 males where each contributed 100 pachytene-stage cells. Chromosomes were identified by blue CREST centromere coloring and yellow MHL1 coloring of crossing over sites. Unfortunately the paper is not so easy to read but they have excellent figures. On average there are 50 cross-overs per set (which is more than I expected). The total number goes down from 52 at age 30y to 46 at age 80y (which may explain the higher chance of aneuploidy at a higher age). Individual crossover frequencies look extremely variable, chromosomal locations are clustering at different site -see my recent blog on recombinogenic sequences. Activity at centromeres was always low while chromosome 21q showed a high individual variablity. Why was there never detailed workup of physical and linkage map? Nay, nay.

Kernel function

Slashdot corbettw writes “This article on Yahoo Science News describes a new finding that explains how the thalamus is used by your brain to essentially boot your brain, and provide for central processing and control of all impulses going to and from the cortex. The article describes its function as an operating system, but from the description it actually seems closer to the functions of a kernel.” That’s true if we see a kernel as abstraction layers for hardware, especially for memory, processors and I/O that allows hardware and software to communicate. It is probably a monolithic kernel that executes all the code in the same address space. Nay, nay.

Role of Faust

-moblog- Edge The Third Culture has a long portrait of Craig Venter: “… His enemies have nicknamed him Darth Venter and accused him of putting the future of biology in jeopardy … journalists have cast him in the role of Faust…” The Celera genome admired in the East Room of the White House had been a composite of 5 different people including Venters own DNA (read about DNA sources). He is now going to make his private DNA public as well as an autobiography. Is anybody interested in reading any of the two? Nay, nay.

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.

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.

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.