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.
Researchers at UCLA and the Howard Hughes Medical Institute tested the feasibility of using the non-coding regions of DNA for gene therapy to treat disease. The researchers discovered that the ability of the LeXis gene, found in the liver, has been found to lower the cholesterol and triglyceride levels in the body. When injected with the LeXis, the mice experienced a significant decrease in the lipid accumulation and reduction of the Strepb2 gene (responsible for cholesterol biosynthesis).
In order to parallel the human conditions of hypercholesterolemia, the mice were on a strict high sodium and high cholesterol diet. Based on their findings, the researchers demonstrated the possibility of using non-coding regions of DNA as an intervention strategy for metabolic diseases.
CRISPR has been all the craze for scientist around the world since it allows for "relatively easy" manipulation of an organism's genome. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. This technology essentially mimics the bacterial immune system to make precise changes to the genome. In Professor Martin’s Lab, at The George Washington University, we have been investigating butterfly wing pattern formation via the use of CRISPR technology, specifically in Vanessa cardui, also known as the Painted Lady butterfly. Lepidoptera is an order of insects that includes moths and butterflies. Butterfly wings are composed of wing scales, which serve as the base for wing color patterns.CRISPR is a genome-editing tool that allows for the deletion and insertion of specific genes with high precision. Moreover, the use of CRISPR genome editing techniques allows for the production and characterization of specific mutations in genes of interest. We have established a protocol to analyze gene function during the development of a non-traditional model organism, the Painted Lady butterfly (Vanessa cardui). The ability to do gene knockouts (eliminate a specific gene) in Lepidoptera was not feasible prior to the rise of CRISPR. The molecular mechanisms for the development of scales are fundamentally unknown since the proper technology for analyzing gene function in Lepidoptera was absent prior to CRISPR technology. With CRISPR we are able to explore this field and expand our knowledge on this subject.
New, ultra-rare gene mutations implicated in eating disorders
September 5th, of 2017 a study was conducted in which scientists were able to observe an extremely rare cluster of mutations, and believe that understanding that pathway better would help in treatment for people with eating disorders. The study was conducted by researchers at the University of Iowa Carver College of Medicine and the Eating Recovery Center in Dallas, Texas. The team was able to show that "targeting the pathway with a drug already approved for diabetes reduces food consumption in a mouse model of binge eating." I thought this article was really cool because there is so much we don't currently understand in regards to how our genes control behaviors like eating disorders. https://www.eurekalert.org/pub_releases/2017-09/uoih-nug090517.php http://dx.doi.org/10.1371/journal.pone.0181556
FDA has approved the first ever gene therapy treatment for patients with B-cell
lymphoblastic leukemia, most commonly found in children and teenagers. The
treatment works by injecting patients with their own
genetically modified immune cells with a virus that targets the source of the
cancer. Current results show that 70% of
the patients who undergo this treatment survive for over a year.Patients with this cancer have a very low
prognosis if they relapse, which makes gene therapy a second chance for families who
thought there was no other option.
The autism spectrum is a developmental disorder that affects communication, social, verbal, and motor skills. Symptoms generally appear in early childhood, and since autism is a spectrum, this means that severity is widely varied. No two autistic people share the exact same symptoms. The American Autism Association states that 1 in 68 American children have some form of autism.
The exact cause of autism is unknown, but studies have shown the disorder is highly hereditary. In a study conducting identical twins, when one twin is autistic, the other twin is autistic 80% of the time, and 40% in fraternal twins. If a single baby is autistic, the chances of their younger sibling also being autistic are only 2-6%, but if a couple already has two autistic children, the chances of the third child being autistic rise to 35%.
There are several studies confirming that autism is in fact at least a partially genetic condition, as researchers have found there are roughly 65 genes strongly related to autism, and 200 genes that have weaker ties. However, no one single gene mutation guarantees autism, as patients in autism studies don’t all have the exact same mutations.
When it comes to genetic mutations, there are common variant mutations, which is a mutation that at least 1% of the population shares, and rare variant mutations, which less than 1% of the population shares, and usually these mutations have stronger effects. Autism is likely caused by many common variants and rare variants working together. Autism can be, and is usually diagnosed, in patients that have no family history of autism. This is called a de novo mutation, or a gene that appears for the first time in a family.
Mutations can be passed down from parents, but de novo mutations usually come from mutations in the ova, sperm, or fertilized ova. Mutations are likely caused by the environment, but it is unknown as to which environmental factors contribute to autism. Many researchers claim that complications at birth and poor maternal health can raise the risk of autism, but neither of these factors guarantee autism, and autism can also happen in a successful pregnancy and birth. Considering that parents don’t remember every aspect of their child’s gestation and birth, reports may be biased based on what the parents think is the explanation for their child’s autism.
A study conducted in 2014 suggest that genes may just be the beginning. This study observed that RNA-sequencing in the corpus callosum in autistic individuals showed extensive gene mis-expression, and that some of the genes that had been mutated affected oligodendrocyte development, which largely populated the corpus callosum. This suggests that genes themselves do not cause autism, but the mutated genes affect entire segments of brain development, which can lead to autism.
There are a few barriers to autism research. Many autistic individuals are unable to legally consent to studies, so genetic testing of severely autistic individuals is limited. Furthermore, autism is usually comorbid with other disorders such as Down’s syndrome, anxiety, and/or ADHD, which could also skew genetic testing. There is a chance that a person diagnosed as autistic has been misdiagnosed, as autism is very similar to a number of conditions, such as Rett syndrome, Fragile X, and Nonverbal Learning Disorder.
Interestingly, in a study comparing the genes of autistic patients to their non-autistic parents and siblings, a mother can have the genes consistent with autism but not have the disorder, but if her son inherits those same genes, he is affected. Does this imply that women need to have more mutated genes in order to be affected by autism? Does this also explain why there seem to be more autistic men than women? Does this mean the X-chromosome is affected by autism, as women have two but men only have one?
American Autism Association. "What Is Autism?" Myautism.org. N.p., 2016. Web.
Deweerdt, Sarah. "Why Don't We Know What Environmental Factors Cause Autism?" Spectrum | Autism Research News. N.p., 26 July 2017. Web.
Li, J., M. Shi, Z. Ma, S. Zhao, G. Euskirchen, J. Ziskin, A. Urban, J. Hallmayer, and M. Snyder. "Integrated Systems Analysis Reveals a Molecular
A recent article in the New York Times describes cases of individuals identifying surprising aspects of their ancestry through direct-to-consumer DNA tests (e.g. 23andme, ancestry.com). The article also summarizes a study comparing self-reported ancestry (via census) and DNA-based ancestry for 160,000 Americans. About 4% of those who checked "white" on the census had partial African ancestry, and this was highest in the southern states -- e.g. 13% in South Caroline. The article does an great job clarifying that ancestry and race are not the same thing. Ancestry is a biological concept, race is a social one.