AP Biology class blog for discussing current research in Biology

Tag: allele

The APOE Gene: little known secret to COVID-19 survival

I’m sure you all have heard it before – surviving COVID-19 is based on your age, sex, and pre-existing health problems – but what if I told you that another factor you should consider is your APOE gene.

A 22K fragment of APOE4 (APOE4) (IB68)

Apolipoprotein E, also known as APOE, is a gene that suppresses the spread of melanoma and is involved in anti-tumor immune responses. 60% of the population has APOE in its most common form, the APOE3 allele, but the other 40% of the population has APOE2 or APOE4. Unlike APOE3, APOE2 and APOE4 negatively impact the immune response against melanoma, and individuals with APOE4 are at greater risk of developing atherosclerosis and Alzheimer’s. These alleles can create such different responses by coding for proteins that differ by just one or two amino acids, which as we learned in AP Biology, can make a big difference in how a protein is structured and functions.

After studying APOE’s impact on the immune response against melanoma, Sohail Tavazoie’s lab at The Rockefeller University grew curious to research if APOE variants impact COVID-19 outcomes. By testing on 300 mice with a mouse-adapted version of SARS-CoV-2, they found that mice with the APOE3 allele were more likely to survive than those with the APOE2 or APOE4 allele. Mice with APOE2 or APOE4 had a less effective immune response, causing more virus to replicate in their lungs, more inflammation, and more tissue damage. The researchers further demonstrated APOE’s impact by analyzing 13,000 patients in the UK Biobank and discovered that patients with two copies of APOE2 or APOE4 were more likely to have died of COVID-19 than those with two copies of APOE3.

With more studies done in the future, clinicians should prioritize that individuals with these alleles receive not only COVID-19 vaccinations and boosters, but also antiviral therapies if they get infected. If testing for which APOE allele you have sounds important to you, you can easily get genetic testing with a saliva sample or a blood test in a commercial lab.

Is the Difference in Size of a German Shepherd and a TeaCup Poodle Due to a Gene Mutation?

Out of all the mammals on the planet, dogs differ in size the most. The biggest dog breeds are around 40 times bigger than the smallest breeds. A recent study has shown that this occurs because of a gene mutation that lies near a gene called IGF1. This gene was originally flagged 15 years ago as playing a major role in the variations of dog sizes. Ancient dogs that were domesticated from wolves in the past 30,000 years differ very little in size, however, in the past 200 years the largest difference in breed size has been recorded as people began to breed the more modern dog breeds during this time. 

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The IGF1 gene was studied comparing to body size of dogs and wild canids. There was one variant that stood out to researchers; this gene mutation was found in a stretch of DNA that works to encode a molecule called a long non-coding RNA. Long non-coding RNAs are a type of mammalian genome that lack protein coding capabilities. Specifically, the long non-coding RNA that was found to affect the size of dog breeds is involved with the levels of the IGF1 protein in the dogs bloodstream. As we learned in AP Biology, mutations in genes occur during the DNA replication phase of mitosis. Mitosis is the division of one mother cell into two daughter cells. DNA replication happens during the S phase of interphase. During this phase, the single stranded chromosome will duplicate and turn into two identical sister chromatids. The mutation will occur when copying the DNA, which would cause the sister chromatids to not be identical. 

This study identified that there are two alleles of this variant. Dogs carrying two copies of the small-bodied allele were most likely to weigh 15 kilograms or less, meanwhile, dogs carrying two copies of the large-bodied allele were most likely to weigh more than 25 kilograms. Dogs that carry one copy of each allele tend to be of an intermediate size. Additionally, dogs containing the larger-bodied allele contain  higher levels of the IGF1 proteins in their bloodstream compared to dogs who carry the smaller-bodied allele. Researchers also recorded a similar relationship in wild canids.

Prior to this study, researchers believed that certain dog breeds were smaller-bodied because of relatively new genetic changes. However, scientists now believe that the smaller-bodied allele is evolutionary and is actually much older than the bigger-bodied allele. They believe this to be true because the smaller-bodied allele was found in coyotes, foxes, jackals, and other smaller canids; this leads us to believe that this allele was present in one common predecessor. More studies must be done to truly determine how these variants impact the levels of  IGF1 proteins in a mammals bloodstream. The IGF1 gene only accounts for about 15% of size variation in dogs, so there is still much more research do be done. This study is just the beginning to really figuring out how we came to have dogs as large as German Shepherds and as small as TeaCup Poodles. Which allele do you think your dog has?


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