Papers of the week (w47)

Dennis' paper of the weekThursday again already? Well, after the positive feedback from colleagues and friends I must continue. I like ambitious goals and hope that the epilepsy genetics community finds this new series on papers of the week helpful. Let’s start with a Science paper by McConnell and collaborators on somatic copy number variations in neurons, a paper that was also mentioned in a recent post. I wanted to know more about the single cell sequencing methodology.

McConnell et al. applied a modified version of an already established protocol (Navin et al., Nature, 2011). After flow-sorting, whole genome amplification (WGA) of DNA followed by massively parallel sequencing is applied. The problem with this method is the unevenness of the amplification during WGA, leading to difficulties in assembling de novo and inaccurate identification of copy number variants (CNV) or heterozygous single-nucleotide changes in single mammalian cells. A recent paper in Nature biotechnology by Gole et al. presents MIDAS (microwell displacement amplification system) as a new and improved method for all kinds of single cell sequencing applications. For us it in epilepsy research, the most significant improvement might be the ability to detect small somatic CNVs in individual human adult neurons with “minimal sequencing effort”.

Why do we sleep? In a new review published in Sci. Transl. Med Yang and colleagues compiled the current understanding of molecular clocks and their connection to human physiology and disease. Given that several seizure types are depending on the time of the day, this knowledge might also be useful in epilepsy research, for example by interpreting WGS generated candidate gene lists.

What keeps scientists motivated? Here is a short comment in the “Science in person series”, easy to read, which might upgrade your coffee break. However, for some people motivation is just the beginning, true dedication to your research starts when you let your body become a laboratory to study the sand fly Tunga penetran. (It’s probably against some law to ask a PhD student to proxy for you). Living on the host this parasite can produce a painful condition called tungiasis that makes it difficult to walk and can lead to other infections.

Are there common variants which confer risk for more than one neurodevelopmental diseases? Several recent meta studies have shown evidence for this hypothesis in the last years. This week a new study suggests that a intergenic SNP significantly predicts postmortem cerebellar gene expression of NDST3 and thereby confers risk to schizophrenia as well as bipolar disorder. Epilepsy may be accompanied by autism or schizophrenia. Therefore, epilepsy-related meta analyses are promising too.

Copy number variations have been shown to be rare but significant risk factors in a broad range of neurodevelopmental diseases including epilepsy. Carvalho and colleagues explored the mutational load near 67 breakpoint junctions and observe a high mutational load owing both to increased de novo SNV and indel mutation rates.

Males, females, mating and the interneuronal signal transmission. The following study published in Cell will inspire some newspapers or TV shows to discuss this topic on another level. Make sure that you know the original cell article: In their study Crickmore and Vosshall demonstrate that male flies are less committed to continue mating with females as the likelihood of mating success increases  and this behavior can be modified by manipulation of interneuron transmission.

This second blog post contained hardcore genomics and general scientific highlights. I hope you like the mix. Otherwise we can always go back to writing about Justin Bieber.