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

Wednesday, October 31, 2018

Variation In The Shape of the Human Birth Canal

The common understanding has been that the shape of a human mother's birth canal has been fashioned by the evolutionary forces that it needs to be wide enough to allow large brained babies to pass through but narrow enough for women to walk efficiently. This evolutionary compromise is known as the obstetrical dilemma. Research by biological anthropologist, Lia Betti, and evolutionary ecologist, Andrea Manica, challenge the obstetrical dilemma. The obstetrical dilemma would suggest that birth canal shape around the world would be relatively standardized but the findings of these researches did not support this. Betti and Manica measured the pelvises of 348 female human skeletons from 24 different parts of the world. They found women from sub-Saharan Africa and some Asian populations has pelvises that were narrow from side to side and deep from front to back. They found that Native American women had wider canals and that Native Americans and Europeans had the most oval-shaped upper canals. They saw that there was less variability in shape in populations farther from Africa.  Their analysis proposed that the variable shapes were due to neutral evolution through genetic drift and migration.  They hypothesized that climate could have contributed to different shapes however they found little evidence for it and suggest further research into other ecological factors.  Betti and Manica said their research could be important for modern obstetric practice in multi-ethnic societies as modern medical understanding is developed mainly on studies of European women.

Maeve Curran

Neanderthal and Modern Human Hybridization

Two researchers, one from the University of Arizona and one from Stanford University, recently published an article in which they analyzed segments of Neanderthal ancestry in the modern human genome related to virus resistance. They ultimately found 152 introgressed gene fragments. They then tested these fragments to try to address their “poison-antidote” hypothesis. Their hypothesis was that as the two species exposed each other to new viruses, they also exchanged virus-interaction proteins (VIPs), which allowed them to have some resistance to these viruses without developing these proteins through natural mutations. These VIPs interact with a variety of RNA viruses such as modern-day HIV, influenza A, and hepatitis C. The specific RNA virus-based VIPs are seen in higher proportions in European than East Asian populations. Most of these introgressed segments in modern humans originated from the second major interbreeding event. This type of analysis of introgressed segments can also be used to detect ancient epidemics. This study can have profound impacts on ancient genetic epidemiology and understanding how these introgressed segments impact the human genome as discussed in recent news articles such as this one.

Joshua Porter

Friday, October 26, 2018

Domestication of the Red Fox

This red fox experiment has been in the works for almost 60 years. The foxes are bred in captivity and then put into one of three groups for genotyping. These groups are the Tame, conventional, and aggressive populations. The foxes have the same window of DNA genotyped, while researchers look for the presence of a "friendliness" gene. Then once the fox's genes have been assessed, a physical test is made to back up the results. What is noted is that the domesticated fox isn't like a dog, they are anxious and curious and they are not like dogs at all. 

Image result for domestication of red foxes

Thursday, October 25, 2018

Mouse pups with same-sex parents born in China using stem cells and gene editing

Researchers from the Chinese Academy of Science were able to use haploid ESCs to create healthy viable mice that has DNA from two mothers; however, mice from male parents survived in utero but only lived for 48 hours outside the womb. The process of creating mice from same-sex parents had been done before, but when the mice from two females were born the first time it was tried with out the use of haploid ESCs they were stunted in growth and did not live very long. The mice created from two males did not even survive birth the over grew in utero and didn't survive birth. This discovery does not mean that haploid ESCs to create same sex offspring can be used in all species of mammals that cannot same sex reproduce because each species has different imprinting sites that have to be recognized and deleted to produce viable offspring, but it is a step in identifying all the possibilities of gene editing and stem cells.

original paper:
Science Daily report:

Post by Sophia Sanchez
According to an article titled, "The Epigenetics of Being Black and Feeling Blue: Understanding African American Vulnerability to Disease", written by Dr. Darron Smith African American are suffering from various mental health serious due to racial discrimination, which remains a societal norm and a routine a part of their everyday lives. It influences human biology and physiology at the cellular level, leaving the poor, the impoverished, and the targeted more vulnerable to chronic disease. The result is epigenetic tags with harmful gene expressions. 

Nana Evison 

Wednesday, October 17, 2018

FDA Lifts Clinical Hold; Green-Lights Vertex and CRISPR’s Sickle Cell Gene Therapy Trial

According to this article published in BioSpace last week (as well as this article from Globe News Wire), in May of this year the FDA placed a clinical hold on an experimental trial for a treatment for sickle cell and other such diseases. The treatment was being co-developed by CRISPR Therapeutics and Vertex Pharmaceuticals, and was put on hold due to "concerns" from the FDA that needed to be reviewed before proceeding in experimental trials. The gene-editing treatment is known as CTX001, and is an ex vivo therapy for people who have inherited disorders involving hemoglobin, like sickle cell anemia or beta-thalassemia. CTX001 edits the genes through CRISPR technology to increase production of fetal hemoglobin in a patient's red blood cells. Fetal hemoglobin naturally exists in newborn babies, but sometimes carries over into adulthood, where it can provide protection for people with blood diseases. CTX001 appears to be safe because it affects only cells at the targeted site (via). The FDA did not say the specific "concerns" that they had, though it is speculated that they are being cautious about human trials because "it's a permanent alteration of a person's genetic code" (Brian Skorney). However, since CTX001 is CRISPR's "most advanced program," it seems that the FDA would rather be safe than sorry with regards to gene-editing treatments, considering potential dangers brought up regarding CRISPR technology in the past.

Ezra Lowe

Reproductive Revolution: how our skins cells might be turned into sperm and eggs

Scientists have recently discovered a way to make somatic cells into sperm and egg cells in vitro in mice (iPSC cells). They do this by injecting somatic cells with a cocktail of genes that generate transcription factors that then tricks the cell to into thinking it is a different type. To turn the cells into gametes, the iPSCs receive chemical signals from the tissues in the ovaries or sperm cells. Once the cells are induced they can then be planted back into the mouse to mature to their full development. This study has not been conducted on humans yet, however, this great of leap in science could lead to genetically modifying human offspring. It would also allow same sex partners to have a genetically related child, and even a single parent to create a child from 100% of their cells.

Tuesday, October 16, 2018

Giraffes Inherit Their Spots From Their Mothers

Though slightly random due to being about giraffes this article titled Giraffes Inherit Their Spots From Their Mothers in the Science News Journal which referenced this study by the Journal of Life and Environmental Sciences which focuses on the spots of giraffes, how they are passed on from one generation to the next and ultimately how that impacts the survival of the offspring. Through photographic samples, parent-offspring regression statistics and field observation of the sampled giraffes the researchers found that there was an inheritable aspect of the spots for giraffe offspring. Those spots do have an impact on survival rates and though the fathers of these offspring were not included the similarity between offspring and parent indicates a correlation between coat patterns and survival rates of the offspring. The researchers found that circulatory and solidity patterns improved overall offspring survival fir neonates and juveniles. While results indicate high similarity to the mothers' coat patterns there are still many things to discover and expand upon with this research and the question of how the spot patterns relate genetically between offspring and mother as well has how those patterns impact survival.

Wednesday, October 10, 2018

High-Resolution Comparative Analysis of Great Ape Genomes

     Leading as the feature article in Vol. 360 of Science Magazine, the Great Ape Genome project was a multi-institutional study involving over 40 scientist who generated higher quality assemblages of genomes from the great apes; humans, chimpanzee, gorillas, & orangutans. By using single-molecule, real-time (SMRT) long-read sequencing technology, the humanizing bias in previous ape genomes have been reduced allowing a more unambiguous view of genetic similarities and differences that arise as the hominin lineage diverged from the great apes. From their data, 10 million years ago the apes genome underwent a segmental duplication expansion where these sections of DNA that repeated were more prone to deletion and duplication mutations which influenced the evolutions of the various species. This support the hypothesis of bigger brain size in humans compared to other apes being due to the up-regulation of synaptic neurons in the prefrontal cortex because the gene for this neuron have been duplicate numerous times in the human genome. This article is the first step to truly understanding what makes us uniquely human because only by getting higher quality ape genome data and comprehensively comparing them can we understand our own genome and genetic difference.

-Denzel Walker

Recent Success of In Utero Gene Editing

In a recent Popular Science article, author Kat Eschner explains the content and future impacts of the Nature paper "In utero CRISPR-mediated therapeutic editing of metabolic genes".  For the first time researchers used in utero base editing to treat a genetic disorder. The experiment was restricted to mice and many more successful studies need to be completed before researchers are able to begin human trials, but there were hopeful results. The researchers found that the mice who were treated in utero for their rare liver disease (HT1) with base editing, thrived in comparison to those mice not treated and even those treated after birth with nitisinone. Furthermore, the edited cells persisted through development. They discovered that Pcsk9 targeting decreased cholesterol levels and Hpd targeting resulted in 'rescuing' the deadly phenotype of HT1. The long term goal for this research is for base editing to be utilized in humans to prevent life-threatening genetic disorders.

Thursday, October 4, 2018

Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose

In this article gene therapy using CRISPR is used to modify the gene that produces the BChE protein. This protein hydrolyzes cocaine in the bloodstream; the unmodified protein is slow and inefficient. Using CRISPR the scientists have modified the gene in stem cells then implanted it back into the body under the skin. It is 4,440 times more efficient at hydrolyzing the drug, cost-efficient, and seems to be a long-term solution to cocaine addiction. The mice with the modified gene no longer craved the drug and were able to survive fatal doses of it. They hope to continue this research by testing on humans and possibly applying the process to other addictions such as alcohol and nicotine.

Tuesday, October 2, 2018

How Child Abuse Can Impact Your DNA

"Child abuse leaves molecular 'scars' in DNA of victim's sperm, new study suggests"

A Harvard study consisting of thirty-four men, twenty-two of which had suffered abuse as children, found a significant difference in the amount of methylation present in the DNA of the abused men versus in the non-abused. Twelve locations of DNA were identified as being consistently affected by methylation in the men who had experienced abuse as children. While the newly discovered information proves how trauma has a long term impact on the abused individual, it also suggests that future generations can also be affected, due to the presence of methylation in sperm cells. The impact is still relatively unknown, but studies conducted with mice have shown that methylation in sperm cells has proven to have negative health impacts in offspring. While there hasn't been enough research done, it's possible that methylation markers could be used in the future in a legal setting as a tool to determine the approximate age of the person who has left DNA behind at a crime scene. The correlations between methylation and child abuse could also one day allow scientists to calculate the probability that someone has experienced child abuse. This study has provided a lot of information to potentially progress what we know about DNA methylation, but Dr. Andrea Roberts of Harvard says that study still remains to be replicated by others.

The Dangers of DNA Testing

A recent article posted in the New York Times discusses the results of a study posted in Forensic Science International, exploring the possibility of error in forensic laboratory DNA testing. 108 different crime laboratories were sent the same DNA sample mixtures and asked to identify possible suspects in a crime. While almost all the labs correctly identified the major contributors of the "crime", 74 labs implicated an innocent third suspect. This study exposed high levels of variation among results received from various forensic laboratories, suggesting a possible need to standardize aspects such as training, etc. While these results do not necessarily imply innocent people are being sent to jail, they pose a question of preciseness of results in complex sample mixtures.

Allie Henderson