This is the blog for GW students taking Human Evolutionary Genetics. This site is for posting interesting tidbits on: the patterns and processes of human genetic variation;human origins and migration; molecular adaptations to environment, lifestyle and disease; ancient and forensic DNA analyses; and genealogical reconstructions.

GWHEG figure

GWHEG figure

Thursday, December 8, 2016

Tasmaninan Devil Milk and its Implications for Fighting Antibiotic-Resistant Strains

Published by Lauren Anderson
The Tasmanian Devil is a carnivorous marsupial that lives in the wild exclusively in the state of Tasmania in Australia.  The species has been described as endangered since the 1980's, which posits ecological threats to Tasmania, as the devils manage the burgeoning feral cat and red fox populations.  Joeys are born extremely underdeveloped, completely lacking an immune system.  They spend the first weeks of their lives inside the mother's pouch- which is a rather unsanitary environment.  To protect against fungi and bacteria inside the pouch, mothers' milk contains powerful cathelicidins, immune compounds produced by mammalian immune systems. While humans only have one form of these powerful antimicrobial peptides, Tasmanian Devils have six! Researchers at the University of Sydney milked captive devils at Devil Ark Conservancy in Tasmania and recreated the six cathelicidins to test against 25 bacterias and 6 fungi.  The fifth cathelcidin wiped out MRSA and the bacteria that causes infant meningitis.  Using these artificial peptides to fight antibiotic-resistant strains may be utilized by pharmaceutical companies in the next few years.
Peel, E. et al. Cathelicidins in the Tasmanian devil (Sarcophilus harrisii). Sci. Rep. 6, 35019; doi: 10.1038/srep35019 (2016).

Sunday, November 27, 2016

A Hint into Canine Obesity

A Hint into Canine Obesity

Eleanor Raffan, a leading geneticist at the University of Cambridge, has discovered a potential correlation between a certain gene and the eating habits of Labradors, a common dog breed in the US and UK. The gene, proopiomelanocortin (POMC), has a specific peptide that play a role in weight regulation. This peptide, Beta-melanocyte stimulating hormone, communicates with the brain to maintain a balance between energy intake from foods and energy output by the body. The variation of this gene found in preliminary studies shows that the expression has been altered in such a way that the dog's hunger cues were turned off, causing the dogs to lose a proper sense of food regulation.

In a follow-up study of more than seven hundred additional Labradors, this variation of the POMC gene was found in about twenty-three percent of the dogs. Furthermore, while all of those dogs with the variant may not have been obese, those with the gene were reported to be more likely to beg and scavenge for food. An evaluation of 38 other dog breeds only showed this gene variation in one type - flat coal retrievers, which are closely related to Labradors. 

William Gibson



Tuesday, November 15, 2016

Teenage Bing Drinking And Its Affects On Brain Function of Future Offspring

Over the past couple of decades it has been made evident that what we do in our lives prior to conceiving a child can in fact affect the mental and physical health of our children. A new study that was recently published suggested that there could be a correlation between teenage binge-drinking and brain function of future offspring. Dr.Pak, his PhD student Anna Dorothea and a few of his colleagues conducted a study on adolescent male and female rats. They exposed a group of adolescent rats to alcohol in amounts comparable to six binge-drinking episodes.

Once these rats were drunk they waited some time. It was important that the affects of the alcohol consumption in the rats went away before any real observations were made. They wanted to really dig into the long term affects of such actions. Once sober the female and male rats mated. All throughout pregnancy the female rats remained sober. Once the babies were born the alcohol rats were compared to a control group of rats that had not been exposed to binge-drinking. Researchers then examined genes in the hypothalamus; a region of the brain where many functions take place including reproduction, response to stress, sleep cycles and food intake. As they were examining the hypothalamus it was seen that there were 159 changes in the offspring of binge-drinking mothers as well as 93 gene changes in the offspring of binge-drinking fathers. In total there were about 244 gene changes in the offspring of mothers and fathers who were both exposed to binge drinking.

This study has been one of the few to show a molecular pathway between teenage binge-drinking and permanent gene expression changes potentially through epigenetic modifications to specific genes. Those Epigenetic modifications can therefore be transmitted to future generations. This test was done in rats so it still remains unclear as to how the results apply to humans. But from what we know, humans are pretty close to rodents on the phylogeny tree. It wouldn't spark a surprise to me if binge drinking actually does have similar affects to the offspring of humans. In today's day and age drinking is an actual epidemic in adolescence. The choices teens make might actually want to be reconsidered after this study.

Monday, November 14, 2016

Fibrodysplasia Ossificans Progressiva - Madeleine Rosenstein

Fibrodysplasia Ossificans Progressiva, or FOP, is a congenital disorder of extraskeletal ossification that affects the soft tissues of the body. This disorder affects 1 in two million people; roughly 285 known cases in the United States. Diagnosed at birth by the hallux abducto valgus deviation hallmark trait, the disease slowly progresses throughout the patient's life. Soft tissues become calcified, leading to trouble moving, breathing and swallowing.

In 2012, the NIH released a study of the involvement of microRNA into the inhibition of BMP (bone morphogenetic proteins) that cause the excess of bone growth. The miRNA, called miR-148a, inhibits the ID proteins, thus decreasing the excessive BMP production. In 2016, a receptor drug called paloveratene is being tested as a "turn-off" signal for excess cartilage production, the first step in FOP prior to bone formation. Using the the miR-148a and paloveratene drug in unison could slow down the progression of FOP throughout their lifetime, however, cannot treat or cure the patient.

Image result for fibrodysplasia ossificans progressiva  Image result for fibrodysplasia ossificans progressiva

Friday, November 11, 2016

Chimps and Bonobos- Susanna Israelsson

“Chimps and Bonobos had a Fling in the Past”

Chimps and bonobos are sister taxa of the genus pan.  They share 99.6% of their genomes, and they split over two million years ago.  While bonobos and chimps have interbred in captivity, this is an unnatural setting and there have been no observations of interbreeding in the wild.  Researchers were inspired by the work Svante Paabo and his team have done with Neanderthal and modern human genomes.  They were curious to see if similar evidence of interbreeding existed in the Pan sister taxa.  They collected DNA and successfully sequenced the genomes of 75 wild apes; 10 bonobos and 65 chimps.

After comparing the genomes, researchers determined that archaic chimpanzees and bonobos interbred 200,000 to 550,000 years ago.  In particular, bonobos mainly bred with central and eastern chimpanzees, which is probably due to geography.  This geography-specific interbreeding is similar to how Neanderthal DNA is present in European and Asian individuals, but not as much in African individuals.  The researchers do theorize that the interbreeding may not have been advantageous for chimpanzees, but more work is required to determine if this is accurate, and why.  

Pan troglodytes

Pan paniscus

Tuesday, November 8, 2016

PDSS2 and The Genetic Basis for Caffeine Tolerance

In August of this year researchers at the University of Edinburgh published a study announcing the previously unknown role of the PDSS2 gene in the genetic basis of caffeine tolerance. After conducting a GWAS on two populations in Italy and one in The Netherlands, scientists found a correlation between coffee consumption and the presence of a variant of the PDSS2 gene. The gene, which is involved in the breakdown of caffeine, was found in a variant form in individuals who habitually drank less coffee than did the other, 'non-variant' participants. This is hypothesized to be because the variant was found to break caffeine down more slowly, and potentially decrease coffee consumption in affected individuals.

While studies on the heritability of caffeine tolerance have been conducted since the 1960s, many only used an additive genetic model. This study utilized a non-additive model in order to consider recessive or dominant genetic effects that might have gone undetected in previous studies. In fact this study was the first to recognize the influence of PDSS2 in caffeine tolerance, potentially due to its different modeling approach. In the future more study will need to be done on PDSS2 to better understand its role in caffeine tolerance, however the study has nonetheless illuminated a new mechanism in the heritability of caffeine tolerance and metabolism.

Regional plot of the results from the association analysis around the most significant SNPs.

Pirastu N, Kooyman M, Robino A, van der Spek A, Navarini L, Amin N, Karssen L C, Van Duijn C M, Gasparini P. 2016. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption. Scientific Reports 6
-Elliot Greiner

Wednesday, November 2, 2016

Genetics of Schizophrenia

Scientists at UCLA have solved a mystery posed by an earlier study conducted on the genetic basis of schizophrenia. Schizophrenia is a serious mental illness that affects millions of people around the world with no lasting cure. A 2014 study determined that 108 loci mutations were were correlated with schizophrenia, but they were located in regulatory regions far from any genes involving the brain. In this 2016 study, it was determined through chromosome conformation capture that these loci are in fact physically close to genes involving fetal cerebral cortex development when the chromosomes are tightly packed, despite being many base pairs away. This process has demonstrated that schizophrenia, although classified as an adult-onset disease, has important fetal components.

C. elegans Program Their Young to Resist Starvatio

Olivia Dias

A study at Duke University took pregnant C. elegant roundworms and divided them into two groups. One group was malnourished, and the other was fed normally. Once the worms had given birth, their offspring were nourished normally. The offspring with well nourished mothers were smaller, while the offspring with poorly nourished mothers were larger and more resistant to starvation and heat. In the next generation of starved worms, less hermaphrodites were born, likely to increase genetic variation in a stressful time.

It's interesting to see that the behavior of these worms doesn't mimic the results of the "Hunger Winter" study, where there were long lasting negative effects for the children of mothers who had been pregnant during the Hunger Winter. The worms bounced back more resistant to starvation, while many generations of Dutch had health problems connected to that specific famine.

Monday, October 17, 2016

A Surprising Family Legacy: The Molecular Scars of Trauma

Studies by Icahn School of Medicine at Mount Sinai, New York City have discovered evidence that supports the effect of trauma over generations through epigenetics and the research of intergenerational transmission of stress effects. If an individual is the descendant of a trauma victim, an example being Holocaust survivors, they will have alteration of their genome. The manipulations discussed range from various changes of specific genes to human response to high risk events, such as cortisol levels. The researchers also speculate that this occurrence happens in individuals who have experienced famine, slavery, and abuse. These trans-generational alterations, from an evolutionary perspective, will produce effects that may be important for survival!

Druonna Collier

Sunday, October 16, 2016

How the Naked Mole Rat Escapes Inflammatory Pain

When most animals get injured or have inflammation, they usually experience thermal hyperalgesia. This is when the surrounding tissue gets puffy and sensitive to heat. However, naked mole rats do not experience thermal hyperalgesia. This is thought to be evolutionarily advantageous for the naked mole rats since they live in crowded colonies underground, which can lead to many injuries. If they did get hyperalgesia, they would be in constant pain. The reason naked mole rats don’t experience hyperalgesia is because their TrkA receptors don’t bind to Nerve Growth Factors properly. Scientists are looking to the naked mole rat and its resistance to pain in possibly treating humans with chronic pain. So far, clinical trials involving blocking the receptors have been successful for people!

-Jenny Huang

Man's Best Friend: A Biological Basis?

Researchers in Sweden have undertaken one of the first projects of its kind, to identify the biological basis for the connection between humans and dogs. To conduct this ambitious experiment, researchers first conducted human-directed behavior tests on a group of 437 laboratory beagles. The beagles were placed in a room with three lidded containers containing treats, and a human participant. The first two containers were designed to be opened easily, but the third was tightly sealed. The dogs were rated on their attempts to seek human help in opening the third container. The primary measures for this were duration of human proximity and duration of human contact. The top 95 and low 95 performers on this task (those who sought out humans the most and least) were then subjected to a GWAS study in which they were SNP genotyped. Researchers then compared SNP genotypes at each locus with performance on the behavior tests. The resulting Manhattan plots are shown here:
Figure 1Figure 2

Four significant SNP loci were found to be associated with seeking human interaction, two were located within the same gene. The genes found to be significantly linked with these behaviors were SCZ6L, ARVCF, and, less significantly, TXNRD2COMT and TANGO2. Researchers discovered that these genes were also known to be associated with social behaviors and disorders in humans. SCZ6L has been associated with autism, and ARVCF, COMT, and TXNRD2 have been associated with schizophrenia. COMT polymorphisms have additionally been associated with mood regulation and aggressive behavior in those with ADHD. This research is important because it reveals more about the genetic basis of human and dog relationships, and therefore more about breeding and domestication practices. Researchers also suggest that the discovery of the same genes linked with social behavior in humans could be useful for using dogs to understand more about human social behaviors. 

Tuesday, October 11, 2016

New Treatment Halts Huntington's Disease Activity in Mice


Research Study:

Researchers have successfully tested a new treatment option that stops the activity of Huntington's for an extended period of time. Huntington's is the result of a mutation in the Huntingtin gene. It is caused by an abnormally large number of CAG repeats, which produce a mutant form of the protein. It affects brain function and causes twitching/jerking.

The treatment includes an injection of a Zinc Finger protein that binds to a DNA sequence. In this study, the used a ZF protein to bind to the CAG tri-nucleotide repeats on the Huntingtin gene in the fourth chromosome. The protein's purpose is to represses the expression of the gene, which in theory should lower the amount of potentially harmful proteins that cause Huntington's.

In mice, the treatment repressed more than 50% of the mutant gene for 6 weeks, and still showed repression after 6 months (23%).

There is no cure for Huntington's and the exact cause in unknown, but researchers think that by attacking the expression of the gene itself, they can slow the progression of the disease. In order to do that, they must try to see how repressing the gene is affecting the symptoms of Huntington's and if the symptoms themselves are being halted long-term or not. They have strong evidence for that, so we may see human clinical trials in as soon as 5 years!

Arash Panjwani

Monday, October 10, 2016

Incoming Revolution to Forensic Palynology

Pollen is everywhere, but certain types of pollen are found only in specific locations and times. This makes pollen and excellent biomarker in criminal and civil investigation. The analysis of pollen for this purpose is called forensic palynology. Forensic palynology, traditionally painstakingly preformed by a highly trained expert equipped with a microscope, may use genetic analysis in the near future.

While DNA barcoding in the past has been ineffective in identifying land plants headway has been made in finding suitable markers. Two genes, matK and rbcL, are the start of a usable system for identification. This in combination with Next Generation Sequencing, NGS, allows for metabarcoding, identification of multiple species at the same time, of pollen and spores an essential process for genetic analysis of pollen to be integrated in forensic palynology.

With these and future advancements, such as a larger reference database for species identification and location and additional complementary markers, genetic analysis should make its way into forensic palynology.

-Olaf B. Corning