Recent interesting facts in genomics!

Human genetic knockouts point to a resilient human genome

According to this paper published in Science, the human genome is more resilient than previously expected and can tolerate a certain amount of disrupted genes without any observable phenotypic effect. The authors "sequenced the exomes of 3222 British Pakistani-heritage adults with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. [...] Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate.".
Interested? Read the full paper: "Health and population effects of rare gene knockouts in adult humans with related parents"

Genetic alterations in regulatory elements could predict personal health history

This paper published on PLoS Computational Biology analyze the impact of personal genetic variants on conserved regulatory elements and how this information could be used to predict health related traits. By analyzing transcription factor binding sites disrupted by an individual’s variants and then look for their most significant congregation next to a group of functionally related genes, the authors found that the top enriched function is invariably reflective of medical histories. As stated by authors these "results suggest that erosion of gene regulation by mutation load significantly contributes to observed heritable phenotypes that manifest in the medical history". They also developed a computational test to interpret personal genomes based on their approach that "promise to shed new light on human disease penetrance, expressivity and the sensitivity with which we can detect them".
Interested? Read the full paper: "Erosion of Conserved Binding Sites in Personal Genomes Points to Medical Histories"

Don't forget about exonic splice-affecting mutations

In this interesting paper on PLoS Genetics authors evaluate the prevalence of splice-affecting exonic variants. This kind of variants are often neglected in the canonical pipelines searching for causative mutations, even if aberrant splicing can obviously have a major impact on gene function. Using MLH1 as a model gene, the authors found that the frequency of this kind of mutations is higher than expected, suggesting that they deserve more attention in future analysisi. Moreover the paper also provide with a comparative evaluation of different in silico prediction alghoritms assessing their performance in splice-affecting variants classification.
Interested? Read the full paper: "Exonic Splicing Mutations Are More Prevalent than Currently Estimated and Can Be Predicted by Using In Silico Tools"

The health impact of your Neanderthal ancestry

Another interesting story published recently on Science journal pointed out the influence of Neanderthal ancestry on human health-related traits. The authors analyzed how alleles inherited from Neanderthals in present European population impact clinically relevant phenotypes and they found associations for neurological, psychiatric, immunological, and dermatological phenotypes. The results indicate that archaic admixture influences disease risk in modern humans, including risk for depression and skin lesions resulting from sun exposure, hypercoagulation and tobacco use.
Interested? Read the full paper: "The phenotypic legacy of admixture between modern humans and Neandertals"

A map of transciptomic cellular landscape in visual cortex by single cell RNA-Seq

This study from Nature Neuroscience used single cell RNA-Seq on more than 1,600 cells to construct a cellular taxonomy of the primary visual cortex in adult mice. Authors identified 49 transcriptomic cell types, displaying specific and differential electrophysiological and axon projection properties, confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties. These results open new perspective on cell level organization within brain tissue, first of all on the potential causal relationships between transcriptomic signatures and specific morphological, physiological and functional properties. Another interesting point, as noted by the authors in to investigate if "certain transcriptomic differences [are] representative of cell state or activity, rather than cell type.
Interested? Read the full paper: "Adult mouse cortical cell taxonomy revealed by single cell transcriptomics"