Multigenerational Effects of Stress in a Rat Model

A recent paper in Hormones and Behavior describes a rat model of social stress and its intergenerational effects. The study investigated the effects of stress (exposure to intruding males) on lactating rat mothers on their offspring and offspring's offspring. These stressed mothers groomed and fed their infants less often, and were more aggressive. Upon reaching adulthood and breeding, offspring females (F1) showed a deficit in maternal care, as well as decreased oxytocin, vasopressin, and prolactin gene expression. Their own offspring (F2) demonstrated decreased social activity as juveniles and adults, as well as depressed plasma corticosterone.The authors propose that this system offers a useful model for human anxiety and depression.

Crosstalk between genetic and epigenetic regulation in a model of stem cell regeneration

An article from PNAS earlier this year examines how adult stem cells regulate differentiation, proliferation and apoptosis through crosstalk between genetic and epigenetic regulation.  These three processes are important in organs and tissues to maintain cell populations that undergo stochastic fluctuations and genetic mutations over the course of a lifetime. The authors take a mathematical approach, without considering molecular details, to show how control strategies of these three processes during cell division may be chosen to maximize expected performance. Their model incorporates the performance functions of stem cells at two time scales: the time of one cell cycle and the lifetime of the tissue. Their model includes a feedback regulation that controls proliferation through both the cell population and heterogenous dependence on the epigenetic states, which is different than the typical feedback model that only depends on the size of the cell population. The model accounts for the elimination of genetically mutated cells by depending on apoptosis at each cell cycle. The authors suggest that this apoptosis maximizes the efficiency of stem cell regulation and demonstrates the cross-talk between DNA variants and epigenetics.

A review of breast cancer genetics and personalized cancer care

The most recent issue of Science was partly dedicated to articles on breast cancer research. One article by authors Couch, Nathanson & Offit reviewed how genetic testing in breast cancer has developed over the past twenty years. They discuss the clinical advancements made from identifying inherited mutations and sequence variants in BRCA1 and BRCA2 and the complexities of determining disease risk when the pathogenicity of sequence variants is uncertain. Many variants of uncertain significance, including missense, intronic and small in-frame insertion/deletion variants, are observed at the BRCA1/2 loci. Current clinical management of breast cancer includes gene expression microarrays to subclassify the disease and serve as prognostic biomarkers, as well as targeted therapy for breast cancers over-expressing the HER2/neu receptor. The evolution of clinical treatment for breast cancer is an example of how genetic testing is a burgeoning field and will allow for more personalized care in the future.

FANTOM project announces mammalian transcriptional "atlas"

In a recent Nature article, the FANTOM (Functional Annotation of the Mammalian Genome) project announced the release of data from a large effort to produce an "atlas" of promotors across cell types in human and mouse. The group performed cap analysis of gene expression (CAGE) via single molecule sequencing across 573 normal human and 128 normal mouse cell samples, as well as human cancer cell lines, human post-mortem cells, and mouse cell types at various developmental stages. This sequencing approach results in sequences of full cDNAs for transcribed mRNAs within cells, including the 5' transcription start site, allowing for the comparison of transcription start sites (TSS) across cell types. The study strongly indicates that gene expression and promotor function is highly cell-type specific, with only 6% of identified genes' expression patterns characterized as "housekeeping," defined as expressed within a 10-fold range in >50% of cell types. This ubiquitously- and uniformly-expressed gene set was enriched for genes involved in RNA processing. Comparison with mouse TSS suggests differing evolutionary patterns for cell-specific v. broadly functioning TSS, with more restricted TSS showing more evolutionary change.

A companion paper published in the same issue looks at enhancer activity across cell types. Data from the project is available online.

40th Anniversary Issue of Cell

This week's issue of Cell celebrates the journal's 40th birthday with a series of insight reviews. These reviews cover a range of great topics on the cutting edge of biology including non-coding RNA, epigenetic inheritance, microbiomes and the immune system, human molecular evolution, and many, many more. Check them out!

Medieval Biological Time Capsules

An analysis of ancient human dental calculus from medieval skeletons published in Nature Genetics allowed a taxonomic survey of dental microbes, as well as dietary components. Notably, the study identified "antibiotic resistance genes" within these dental microbiomes, providing additional evidence for the antiquity of such genes. You can also read a news piece on the research.

The epigenetic basis of complex traits in plants

In the March 7^th issue of Science Cortijo et al. are able to quantify the impact of heritable epigenetic variation on traits in the model plant Arabidopsis. They used inbred plant lines that share identical DNA, yet have differentially methylated regions (DMRs). They showed that DMRs can be stably inherited independently of DNA sequence changes and function as epigenetic quantitative trait loci (QTL). Several of the DMRs acting at epigenetic QTL accounted for 60-90% of heritability for two complex traits, flowering time and primary root length. The detected epigenetic QTL have all the necessary phenotypic properties to become targets of natural or artificial selection. The authors suggest their findings are a component of the so-called “missing heritability.”

New finding that humans can detect over 1 trillion different olfactory stimuli

In the current issue of Science Bushdid et al. find that humans are able to discriminate at least 1 trillion olfactory stimuli. This finding far exceeds the previous estimates that humans can detect only 10,000 different odors. The authors used combinations of 128 odorous molecules to determine how many unique stimuli exist. They performed tests with human subjects to determine the discriminability of mixtures that varied in the percentage of odor components and from there applied a theoretical framework to determine the number of unique olfactory stimuli. They found a large discrepancy between the abilities of subjects to discriminate different mixtures, and they believe their estimate of 1 trillion distinguishable olfactory stimuli to be a conservative one.

Craig Venter launches Human Longevity, Inc. to combat age-related diseases

Yesterday, March 4th, Craig Venter and entrepreneur colleagues announced the launch of their new company, Human Longevity, Inc. (HLI). The company plans to sequence massive numbers of full human genomes, as well as the DNA of human-associated microbes and pathogens, to discover the bases of aging and degenerative diseases. HLI's goal is to sequence 40,000 human genomes in the first year and the first disease to be targeted is cancer. This announcement was featured in many popular new sources, including The New York Times. 

Thrifty Gene

The "thrifty gene hypothesis" was proposed in 1962 and stated that poor fetal and infant growth, combined with existence of Type II Diabetes, would cause permanent glucose metabolism problems.  It was believed that this genotype would confer an advantage in hunter gatherer societies where such individuals would gain a lot of weight in times of food abundance, but still be able to survive during scarcer times.  This recent article in the American Journal of Human Genetics describes a study which explored positive selection for loci known to be associated with Type II Diabetes.  All data was gathered form previously published GWAs.  They conclude that past positive selection was NOT a driving force in prevalence of Type II Diabetes in the current population.

http://www.cell.com/AJHG/abstract/S0002-9297(13)00580-6

Taboos in Genetic Research

A feature in Nature last fall sought to open a discussion regarding whether or not scientists should avoid undertaking research into "taboo" subjects. The subjects considered in the piece were intelligence, race, violence, and sexuality. Noting a sordid history of pseudoscience with devastating sociopolitical consequences, particularly in the case of the first two topics,  the author recounts the stigma experienced by contemporary researchers attempting to apply what they believe to be rigorous scientific methods to the study of related subjects. Accompanying public polls on Nature's website indicate that readers believe that these subjects should not be avoided.

An interesting response piece in Scientific American can be read here.

Identifying Neandertal DNA in modern human genomes

In the most current issue of Science authors Vernot and Akey identified Neandertal DNA in modern humans using whole-genome sequences from 379 European and 286 East Asian individuals. They used a summary statistic to identify candidate genes that was sensitive to the signatures of introgression. Their results yielded more than 15 gigabases of introgressed sequence that spans around 20% of the Neandertal genome. Their results also indicate that Neandertals were a source of adaptive variation for loci involved in skin pigmentation. This fossil-free paradigm of sequencing archaic genomes holds promise for the study of hominin evolution and identifying uniquely human genotypes and phenotypes.