Rosey Cheeks from a Glass of Wine?

Do you look like you are blushing after drinking a glass of wine or beer? I know my face gets pretty flushed within those first couple of drinks. This characteristic happens to indicate part of your genotype. Depending on the genes you possess, you may be more or less susceptible to the affects of alcohol.
After consumption of alcohol, the alcohol dehydrogenase enzyme (ADH) works to break down the ethanol into acetaldehyde inside your liver (Kim et. al, 2005). Another enzyme known as aldehyde dehydrogenase-2 (ALDH2) then turns the acetaldehyde into acetic acid (Kim et. al, 2005). Acetaldehyde is the toxic byproduct of ethanol which the enzymes in the liver work to detoxify. In some cases, a mutation occurs in the ALDH2 gene where there is a substitution of a nucleotide pair (Kim et. al, 2005). The nucleotide goes from a G to an A and results in an amino acid change from Glutamine to Lysine which causes a loss of function of ALDH2 (Kim et. al, 2005). People with this mutant gene experience flushing of the face, tend to get sick, have headaches, or sweat after ingesting alcohol (Kim et. al, 2005). The build-up of acetaldehyde in the tissues and the body's inability to convert this toxin to acetic acid due to lack of ALDH2 activity causes these sickening symptoms. It has been found that many people of Asian descent possess this mutated ALDH2 genotype which is why they tend to have a much lower alcohol tolerance than people of different nationalities. Kim et. al (2005) looked into whether there may be more to the genotype than either having a fully active gene or a completely inactive gene. They believe that the ALDH2 activity could be a result of inheritance from both parents. In this case, a range of genotypes could occur where some people are homozygous for normal ALDH2, some are heterozygous (1 normal ALDH2 and 1 mutated ALDH2), and some homozygous for the defective ALDH2 (Kim et. al, 2005). Kim et. al, (2005) performed a study where they looked at people with each of these genotypes and measured whether alcohol intake resulted in a flushed face. After drinking one beer, 6.5% of the people with active ALDH2, 92.3% of heterozygotes of ALDH2, and 100% of homozygotes for the defected ALDH2 gene all demonstrated flushed faces (Kim et. al, 2005). The study showed the variation in phenotypes as a result of differing genotypes and that each genotype corresponds to a different level of ALDH2 activity (Kim et. al, 2005). Although complete inactivity of ALDH2 is commonly found in people of Asian background, members of other origins may exhibit decreased acetaldehyde detoxification as a result of a heterozygous genotype.
Next time you are drinking, look into the mirror after you first glass of alcohol. A red face may indicate that your body isn't getting rid of the acetaldehyde as fast as it should, and that it may be building up in your blood and tissues. Your visible phenotype may be a signal to what your genotype is and prevent you from drinking more alcohol than your body can tolerate.

New Leukemia Treatment (Ma et. al, 2014)

Studying the genome of different organisms leads to the discovery of many different cellular processes and how certain phenotypes are influenced. Whenever I think about mutations or alterations in gene expression I immediately think of diseases. Genetic research does lead to the understanding of different diseases, but it also leads to knowledge on how to treat these disorders. Once scientists are able to narrow down the genes and specific gene functions that influence a particular disease, they can then work at finding a way to alter gene regulation in order to treat the disease. The study of Acute Myeloid Leukemia (AML) is an example of how scientists have taken what they know about gene expression in order to treat individuals with the disease.


Acute Myeloid Leukemia is a disease where underdeveloped blasts grow within the bone marrow and peripheral blood as a result of the cell's inability to differentiate (Ma et. al, 2014). Ma et. al (2014) explains how, "FMS-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that is expressed in stem cells." When FLT3 binds it results in the activation of phosphorylation of proteins and also triggers other pathways within the cells (Ma et. al, 2014). A mutation occurs in individuals with Acute Myeloid Leukemia where FLT3 is activated without having to be bound to the ligand (Ma et. al, 2014). There are a couple different mutations that have been found to affect FLT3, but the most widely known case is when there is an internal replication of different lengths of the sequence (Ma et. al, 2014). This activation allows for continued growth of the cells which is seen in Acute Myeloid Leukemia. Ma et. al (2014) as well as other scientists are trying to find something that will inhibit FLT3 in order to treat individuals with this disease. Currently TTT-3002 is under observation as a possible new inhibitor that may be able to treat Acute Myeloid Leukemia (Ma et. al, 2014). Ma et. al (2014) believe that TTT-3002 prevents FLT3 activity by producing mutations on residue D835. TTT-3002 has been tested in mice, and so far, has been able to inhibit FLT3 containing multiple mutations, as well as working against blasts within the bone marrow and blood that express FLT3 (Ma et. al, 2014). It seems to be the strongest acting treatment to date that does little harm to the host (Ma et. al, 2014). This occurs as a result of TTT-3002's selectivity to FLT3 allowing it to more directly reach the target intended. Although this inhibitor is predicted to hold up against resistance from FLT3, studies have recorded that its effects are more damaging when doses are paired with chemotherapy (Ma et. al, 2014). TTT-3002 has more promising effects on Acute Myeloid Leukemia when it is the sole treatment. Trials on human patients are now under way, but there is still much research that needs to be done on this inhibitor and its capability to treat Acute Myeloid Leukemia.

Pleiotropy (Stearns, 2010)

As I mentioned last week, this post will shed some light onto the concept of pleiotropy. Pleiotropy was seen to play a role in the psychiatric disorders discussed last week, but it was never clearly stated exactly what this means. I've found some information on the history of pleiotropy and how its definition has evolved in science over the past few years and will probably continue to evolve as more information is discovered.




Pleiotropy is when a locus on a gene has control over multiple phenotypes expressed by that organism (Stearns, 2010). Stearns (2010) describes pleiotropy as a type of mutation that can be observed as different phenotypes arise from a change in one gene. This phenomena is hard to distinguish from phenotypes linked by similar genes, but pleiotropy is still believed to greatly influence, "aging, selection, adaptation, speciation, and human disease" (Stearns, 2010). We saw one example of its role in psychiatric disorders last week. The idea of pleitotropy dates all the way back to Gregor Mendel's first workings with genetics (Stearns, 2010). He observed the linked inheritance of seed coat color, flower color, and axial spots on a plant and believed that these traits must have been expressed by the same gene (Stearns, 2010). Mendel didn't specifically come up with pleiotropy, but he did introduce some of the first thoughts on the matter. Ludwig Plate studied genetics further and is the person who gave the idea of pleiotropy its name (Stearns, 2010). He explained how a pleiotropic gene would express multiple traits and that because these traits were all associated with one gene, they would always be correlated with one another (Stearns, 2010). Later research led to the discovery that a locus could have multiple reading frames that translated to different proteins (Stearns, 2010). This occurs through alternative stop/ start codons and alternative splicing within the locus (Stearns, 2010). Differences in the start and stop codons in the locus cause varied forms of proteins which, in turn, lead to different functions and multiple phenotypes (Stearns, 2010). On the other hand, alternative splicing cuts out different exons which lead to varying proteins (Stearns, 2010). If the different combinations of exons from the same locus are spliced then this results in multiple proteins which is seen as pleiotropy (Stearns, 2010). It is believed that many genes exhibit pleiotropic effects in that they correspond to multiple proteins, but of this large quantity, only a few genes actually express differences in multiple phenotypic traits (Stearns, 2010). Pleiotropy can lead to both increased and hindered adaptation of populations in an evolving environment depending on the circumstances (Stearns, 2010). In some cases it may allow species to develop newly adapted traits with ease, while at other times the multiple functions associated with a specific gene will prevent evolution from targeting the specific function that needs to adapt (Stearns, 2010). Scientists are still studying pleiotropy and its roles in evolution.