How Do You Study for a DNA Test?

October 18, 2019

How Do You Study for a DNA Test?

Week 2 of LEDGE’s second session was of great fun! This week, the student’s learned about genetic testing methods and karyotyping. We started out the workshop with a set of case studies examining what students thought they knew about genetic testing. For example, the students were told that a couple had recurrent miscarriages and asked who they should see to discuss next steps. Among many amazing answers, a fertility specialist and a genetic counselor were the best replies! Students also learned what a genetic counselor does, risk factors that increase the likelihood a child is born with a genetic abnormality, and about all the types of genetic testing that are available.

Kathleen Lecturing

“…This brought us into a discussion about designer babies, the idea that you can pick out traits that you want in a child such as intelligence or athletic ability.”

One student asked about a type of testing she described as, “genetic testing on an embryo before it is put in the mother’s body.” While I was blown away that a middle school student even knew what this was, I happened to know a little about it from a tenth-grade research project I did (I was a nerd, I know). What she described is known as Preimplantation Genetic Diagnosis (PGD). PGD is used in concert with in vitro fertilization (IVF), an assisted reproductive technology. The in vitro fertilization is performed creating the embryo. This embryo is then tested before it is implanted (hence preimplantation) for any genetic abnormalities (hence genetic diagnosis). This question brought us into a brief discussion about designer babies, the idea that you can pick out traits that you want in a child such as intelligence, athletic ability, and hair color. I kindly reassured the students that there are regulations in place that limit the use of technologies such as PGD for only purposes necessary to the health of a child. I also highlighted that the thought of designer babies was born out of the public’s lack of genetic literacy and understanding of impact, emphasizing the need for their participation in LEDGE!

Student Proudly Showing Off Work

We then moved into the next phase of the workshop: karyotyping. The students learned quickly how time consuming and tedious putting together a karyogram can be. Whenever they looked at me with confused and tired eyes, I would share the story of my Laboratory in Cytogenetics class where I would cut out each chromosome by hand and glue it to a paper. Even better, I told the students to imagine the chromosomes clumped together in a bundle, with nearly indistinguishable banding, and trying to do the same thing they were doing under a microscope and for a grade. They quickly stopped complaining and even came to do a great job on their karyograms, with each person correctly completing two!

Student Holding Clipboard of Work

“…The students learned quickly how time consuming and tedious putting together a karyogram can be”

We wrapped up with a presentation by Dea Gorka, a graduate student in Dr. Stormy Chamberlain’s lab at UConn Health. Her research focuses on Angelman Syndrome, an imprinting disorder caused by a deletion on the maternal allele (or having two copies of a paternal allele and NO maternal allele called uniparental disomy) of the gene UBE3A on chromosome 15. Dea explained how a deletion of this gene on the maternal allele will cause an excitable and hyperactive phenotype with impaired cognitive abilities. In contrast, a deletion of this same gene on the paternal allele (or uniparental disomy of the maternal allele) can cause Prader-Willi syndrome, characterized by an insatiable appetite, temper tantrums, and compulsive behavior. Another disease, 15q duplication syndrome, along with Angelman and Prader-Willi are being studied by Dea and the rest of Dr. Chamberlain’s lab using induced pluripotent stem cells (iPSCs) to understand cellular phenotypes in the different diseases as well as regulation of imprinted gene expression. I can’t wait to see what fun stuff we learn next week with cancer genetics!

Published 7/24/2019 by Kathleen Renna

Michael Phelps for a Day

Michael Phelps for a Day

Our last day of LEDGE in the second session was one to be remembered. We had a great discussion about performance and exercise genetics followed by each student building their best athlete using online resources. Initially, students shared ideas that they believed would contribute to your ability to exercise and how your genotype may affect that. Suggestions they made included strength, endurance, and muscle mass, but we also discussed variables like biomechanics and hydration. It was also a great discussion about what diseases they thought may be affected by amount of exercise. We talked about a particular study identifying aerobic exercise as a mechanism for slowing Alzheimer’s progression, however students talked a great deal about obesity, hypertension, and more. We also talked about the potential to test for genes that improve athletic performance. Just because you have a gene that makes you good at, say, lifting weights, does NOT mean you should drop everything and become a bodybuilder. There are a lot more factors that go into your performance than that!

Students around table

“…Something everyone learned was how tedious database searching is, but this is one of the skills you need as a geneticist!”

Our young scientists then moved into the Build Your Best Athlete portion of the day where, similarly to the high school students, they used online databases such as GeneCards and Genetics Home Reference to determine genes that may improve athlete performance. Hot genes were ACTN3 and ACE, two genes with variants often found in elite power athletes. One student chose to build a swimmer and found a great article on all of the “weird” variations that Michael Phelps has that make him so insanely good at swimming. His height, wingspan, and a genetic variant that allows him to produce half the lactic acid (the build-up of which leads to soreness in our muscles after exercising) that a normal person does has led him to becoming one of the greatest athletes of all time (read more here). Some other students designed soccer players and hockey stars. One thing that everyone learned was how tedious searching through databases can be, but this is one of the fundamental skills you need as a diagnostic genetic scientist!

Student Working on Laptop

We rounded out our session with a great presentation by Lauren Corso, a PhD student in Kinesiology at UConn as well as a former D1 volleyball star during her undergraduate years. She shared a bit about her experiences, showing kids some funny pictures of her when she was little being a giant compared to her peers. Eventually Lauren began playing volleyball, although she was an all-around great athlete (maybe it’s in her genes??) in whatever sport she played. After her athletic career came to a close upon graduation from undergrad, she still highlighted her need to continue in athletic endeavors. So, she picked up rock-climbing (and was naturally good at that too!). At the same time, exercise genetics interested Lauren during her studies at UConn, and so she enrolled in the kinesiology graduate program where she intends to get her PhD.

Picture of participants

“…I learned a lot about my interests and how to share genetics information with a wide range of individuals.”

At the conclusion of Lauren’s talk, we all went outside for some much-needed fresh air and a photo shoot. It was great to hear from the students what the highlights of the program were for them and what they were taking away from the experience. It has been an incredible journey for me as well – I learned a lot about my interests and how to share genetics information with a wide range of individuals. I met some brilliant young gene-iuses who are going to leave a great impact on the world as we know it, and I met a lot of great parents who helped shape them as well! Thank you to all who have participated… Til’ next summer!

Published 7/24/2019 by Kathleen Renna

Can I Offer You a Side of Chips?

Can I Offer You a Side of Chips?

This week at LEDGE, students learned a bit about cancer genetics followed by a DNA microarray activity comparing normal and patient cells. To start, students answered true or false questions about cancer, learning about viruses that may cause cancer, various risk factors for the disease, and the five main categories of cancer. We eventually got to a question where the students were asked if cancer was a heritable disease… What do you think?

Students Discussing

“…students answered true or false questions about cancer, learned about cancer causing viruses, and the five cancer categories.”

Yet again, the students learned that the most common answer in genetics is “it depends.” Some cancer disorders, such as Li-Fraumeni syndrome or Lynch syndrome, are hereditary and can be passed on to offspring. However, most cancers are not hereditary and will not be passed on to your children. That does not mean that cancer is not a genetic disease. Cancer occurs due to a malfunction of one, some, or many genes that leads to one of the six hallmarks of cancer that students learned. These are still genetic mutations making cancer a genetic disease, but most of these mutations will not be passed on to offspring making most cancer cases not heritable. For the cases of cancer that are heritable, the students took some guesses as to how to identify familial cancers. Some correct answers include seeing the same cancer in many family members, having multiple tumor types in the same person at the same time, and getting cancer at an early age.

Student Working Diligently

From here, we moved onto our exercise of DNA microarrays. Students were able to add equilibration buffer, control DNA, and hybridization buffer just like a real microarray protocol. We were even able to look at real microarray chips (hence the title, hopefully you get the pun now!) that have been used in experiments, but we had to imagine them being plugged into a computer to visualize the result. These lovely ladies also had to master the art of patience, as there were several incubation periods. Luckily, I was able to learn a bit about the student’s career goals, which included a vet, cardiothoracic surgeon and a good ole rabbit breeder. I was also fortunate to have Dr. Lisa Brailey, our professional woman in genetics that week, who came prepared with some fun facts about microarrays. One thing that I learned from her was that the person who invented microarrays, Dr. Patrick Brown, was the same person who founded the open access Public Library of Science (PLoS) database as well as the Impossible meat franchise (the burgers that bleed!). After much waiting, our scientists were able to visualize the microarrays under UV light, where they could see the green, yellow, red, and blank spots. The different colors represented different expression profiles of various genes, whether the patient’s gene expression was higher, lower, the same or negligible compared to the control sample. From this, students learned how to interpret array results that may come back from a patient who had their tumor tested, and how the expression differences may represent tumor suppressor genes, oncogenes, or housekeeping genes.

Professor Giving Lecture

“…If you have a career goal in mind in a particular field or location, try and get there soon and work your way up the ladder by starting closer to where you need to be.”

We wrapped up the workshop with Dr. Lisa Brailey sharing a bit about her life experiences. She was the lab director of a molecular diagnostics laboratory for nine years and is currently searching for new opportunities. Lisa expressed to students the need to start in an area you plan to land in. What she means by this is if you know you have a career goal in mind in a particular field or location, try and get there soon and work your way up the ladder by already starting closer to where you need to be. We thank Lisa for speaking with us and wish her the best in her future career!

Published 7/24/2019 by Kathleen Renna

What’s in Your DNA?

August 8, 2019

What’s in Your DNA?

Our first LEDGE workshop of the second session went off without a hitch! We had eight incredibly smart middle school (and some rising high school) students join us for an introduction to genetics. When I say that these kids are gene-iuses, I truly mean it! We began by discussing if certain traits and habits were genetic. It brought about a great debate about what it means for something to be genetic. Many thought that if something was done out of habit, there was no genetic component, as with the way you cross your arms. Some also believed that if you did not have any control over the outcome, it was a genetic characteristic, like whether or not you have dimples. Just like last session, these students learned the number one response in genetics: it depends! Some traits may have a gene, or several, associated with them, but often can be changed as a result of environmental factors.

Students listening to discussion

Another important conversation we had was the difference between the terms “genetic” and “hereditary.” Students went back and forth with one another to determine what the definition of each was. They came to the conclusion that something being “genetic” simply means that whatever it is has to do with your DNA, whereas “hereditary” means that the trait, feature, etc. will be passed down from parent to offspring. Not everything that is genetic is heritable, but things that are heritable are genetic… Confusing, I know.

“Students learned that eye color is polygenic; some even knew that brown eyes are caused by a build up of melanin”

We also went around the room to share some polygenic traits and multifactorial diseases that people could think of. Students learned that eye color is polygenic, and some even knew that having brown eyes was due to a build up of melanin. How did they get so smart?? They mentioned traits like height and hair texture and diseases like cancer and diabetes which fall into these categories.

Students swishing saline solution

“Each student got a ton of DNA – great saline-swooshing skills, kids!”

Next up was DNA extraction, which most students had not done before. Each scientist learned a bit about the different steps of DNA extraction, like what protease does and what a centrifuge is used for. In between incubation periods, we had the opportunity to also talk a bit about the structure of DNA. DNA is made up of four bases – adenine, thymine, guanine, and cytosine. The nucleotides of DNA are held together by phosphodiester bonds (say that three times fast!) to make a whole strand and two strands of DNA are held together by hydrogen bonds between the bases of each strand. All of this comes together to make a DNA molecule in the shape of a double helix. The students knew so much and were still excited to learn more, my favorite part! Once all the incubation steps were complete, we stained our DNA and were able to see it as white clumps in our tube. Each student got a ton of DNA – great saline-swooshing skills, kids!

Students examining results

We wrapped up our first workshop by chatting with Nicole Pauloski, a research associate in the O’Neill Lab at UConn. Nicole shared her experiences traversing between various disciplines, whether it be biotechnology, genetics, you name it. She spent some time following her master’s degree working in industry, but eventually realized she wanted to give back to students. So, Nicole began working in a cytogenetics laboratory in Storrs which also afforded her the opportunity to be a professor for some graduate courses. With an incredibly diverse background, Nicole demonstrated to the students that there are so many ways to combine your passions, so never feel stuck in one place because there is always something new and exciting that could come next!

Published 8/7/2019 by Kathleen Renna

Our Last Time ~Exercising~ Our Brains in Session One!

August 7, 2019

Our Last Time ~Exercising~ Our Brains in Session One!

Sadly, our first LEDGE session wrapped up on Saturday, but it was a fun day to explore performance and exercise genetics! Dr. Amanda Zaleski, an exercise physiologist at Hartford Hospital and a former Husky, shared a bit about how she landed in her career and what she studies now. She pointed out to students an important point – what you think you want to pursue as a career right now may not be what you end up doing. Dr. Zaleski wanted to be a forensic scientist but, after some experience in the field, she decided to pursue kinesiology and exercise genomics. In this field, she studies how someone’s strength, hydration levels, and blood biomarkers (among other things) change when a person exercises with a certain genotype.

Two students reading slides

To make her case, she shared a video based on a study that linked exercise with positive outcomes in Alzheimer’s disease patients. Dr. Zaleski also shared an interesting study performed at Hartford Hospital on marathon runners. Some runners, seemingly in peak physical condition, become very sick after running a marathon. The cause? These athletes have the rare genetic condition Factor V Leiden, which increases a person’s risk of developing a blood clot. This study at Hartford Hospital showed that if marathon runners wore compression socks while racing, it lowered their risk of developing a blood clot. A huge feat for performance genetics!

Students thinking

“Vissy, a midfielder on the UConn Women’s Soccer team, and David, a member of the UConn Track and Field Team, shared a bit about their training regimens”

After hearing about factors that impact an athlete’s performance, students had the opportunity to hear from two elite athletes themselves! Vissy, a midfielder on the UConn Women’s Soccer team, and David, a member of the UConn Track and Field Team, shared a bit about their training regimens and the different aspects of fitness they had to develop to become elite, such as strength, endurance and stamina. They also discussed a bit about their lives as student athletes and how to effectively balance work and play (literally!). Thanks for coming Vissy and David!

Student showing off diagram

“Students modeled their athletes after ones they admired, like swimmers and American Ninja Warriors.”

We rounded out our final workshop with students “Building their Best Athlete” which consisted of using genetics databases to find genes and variants that one may find in a high-performing athlete. Students chose to model their athletes after ones they admired, like swimmers, rowers, and even American Ninja Warriors. These young scientists believed that certain athletes need an active version of the ACTN3 gene for enhanced muscle strength or a certain polymorphism in the PPARA gene to improve endurance. Many students found out how tedious database searching can be but also how useful it is having all your information in one place!

Student group photo

“Our first LEDGE session was a success in my eyes, with high hopes that all in attendance had a fun time while also learning a bit along the way!”

Our first LEDGE session was a success in my eyes, with high hopes that all in attendance had a fun time while also learning a bit along the way! Big shout out to all of my wonderful professional women in genetics and volunteers who came out to assist this month. I can only hope my August workshops with middle school students are just as fun!

Published 8/7/2019 by Kathleen Renna

Hip Hip (Micro)Array!

July 26, 2019

Hip Hip (Micro)Array!

This past weekend, LEDGE skimmed the surface of cancer genetics. We began by playing a round of true or false, posing options such as, “cancer can be passed from one person to another” and “all forms of cancer are heritable.” The answer to both of these is “false,” however these students know now more than ever that there are always exceptions to every rule. There are viruses, like human papilloma virus (HPV) and Epstein-Barr virus (EBV), that can manipulate the genome and cause cancer to occur. These are viruses that many people encounter during their lifetime that can be transmitted from person to person. Similarly, there are some forms of cancer that can be passed onto offspring; however, this is a very small percentage of the total number of cancer cases that occur. A point I also wanted to make clear to the students was that cancer is, in fact, a genetic disease. Although it may not always be heritable, the disease still alters parts of your genome to “make itself” happen. Therefore, things can be genetic, just not always heritable.

“…we all chatted about what the students want to be when they grow up and (equally as important) whether they think storming Area 51 is a good idea”

Students then learned about microarrays, a common technique used in clinical laboratories to study gene expression. In cancer patients, a microarray may be performed to look at their tumor gene expression profile versus their normal sample. Students used microarray cards to detect the gene expression of their own patients. If anything, LEDGE has taught students that there is a lot of “hurry up and wait” in science. In between incubation steps, we all chatted about what the students want to be when they grow up and (equally as important) whether they think storming Area 51 is a good idea. After all reagents were added, we visualized our microarray using UV light. Green indicated lower gene expression in the tumor sample than in normal cells, while red meant expression was higher. Yellow indicated that gene expression was the same in both samples, suggesting that this was a housekeeping gene. Students wrote down some of their observations in lab notebooks and we then moved on to our final portion of the workshop.

Some students had normal human karyotypes with no abnormalities, while others may have had trisomy 21 or Klinefelter’s syndrome. Other students were (un)fortunate enough to have to piece together a chimpanzee karyogram. The point of this exercise was not only to teach students about karyotyping, but to highlight the similarities between us and other primates.

“She described the need for more people in our career track and highlighted the benefit of becoming a bioinformatician: they are in such high demand that places will pay you anything to work there”

Dr. Elizabeth Ewen, a Ph.D. scientist who serves as the Genome Software Manager for Agilent Technologies, shared with students a bit about her background. Dr. Ewen is a Diagnostic Genetic Sciences graduate who started out into the workforce a bit unsure of where she would end up. She worked at Brigham and Women’s Hospital in Boston for three years as a cytogenetics technologist before she decided to attend graduate school for molecular and cell biology. With this degree, Dr. Ewen worked in various corporations as a Field Application Scientist before she settled, and got promoted to manager, at Agilent. She described to students the need for more people in our career track, and even highlighted the benefit of becoming a bioinformatician: they are in such high demand that places will pay you anything to work there. Dr. Ewen also talked about her ability to work from home, allowing her to raise a family while also being a manager. Her company also pays her to fly to places like Australia and Argentina for work, which she sees as a huge benefit to going into the field. Students seemed interested in Dr. Ewen’s talk, and hopefully they consider all the career options related to our field!

Published 7/24/2019 by Kathleen Renna

What is a chromosome’s favorite article of clothing?

July 25, 2019

A Pair of Genes!

Our second LEDGE workshop was very exciting! With thirteen kids in attendance, Maria Guyre, a genetic counselor, shared a bit about a day in her life. Maria explained why a family or person may seek out genetic counseling, whether it be due to a condition they don’t want to pass on to their child or they are displaying symptoms associated with a known genetic disorder. She then went on to discuss how someone can become a genetic counselor, starting with getting your undergraduate degree all the way to exploring and applying to master’s programs. Maria highlighted the high job satisfaction rate for genetic counselors and, with an increased need for more to enter the field, job prospects look promising. The key takeaway from our discussion was that genetic counseling is a diverse career with many fields and positions available, so you will never get bored!

genetic counselor

“The key takeaway from our discussion was that genetic counseling is a diverse career with many fields and positions available.”

 

We then went through some case studies that put the students in a genetic counselor’s shoes. We talked about things a doctor may see on an ultrasound that would prompt the need for a genetic counselor, such as an omphalocele, to what noninvasive prenatal screening (NIPS) is and who may be able to use it. Genetic counseling is not only for parents looking to conceive – you can seek genetic counseling for cancer, adult abnormalities, and even neurological conditions. We also went over some of the ways someone may be tested for a genetic condition, whether it be through sequencing, Southern blot, or, as we learned in this week’s dry lab session, karyotyping.

student karyotyping

Some students had normal human karyotypes with no abnormalities, while others may have had trisomy 21 or Klinefelter’s syndrome. Other students were (un)fortunate enough to have to piece together a chimpanzee karyogram. The point of this exercise was not only to teach students about karyotyping, but to highlight the similarities between us and other primates.

karyo queen

“Other students were (un)fortunate enough to have to piece together a chimpanzee karyogram.”

A chimp chromosome 5 looks a lot like a human chromosome 6, and their chromosome 1 looks just like ours except flipped upside down. The students agreed that the work was tedious, however it was definitely a good insight into a diagnostic genetics’ technique.

Published 7/24/2019 by Kathleen Renna

Diving Off the LEDGE into a World of Diagnostic Genetics!

July 9, 2019

Diving Off the LEDGE into a World of Diagnostic Genetics!

Our first LEDGE workshop was held this past Saturday and it went off without a hitch! We welcomed nine wonderful students to the Storrs campus to get an introduction to genetics and polygenic traits! We started off the session by talking about some frequent “genetic myths,” or traits that people think are genetic but really aren’t. Students learned that features such as dimples, cleft chin, and whether your ear lobes are free or attached to your head are not considered genetic. We also learned about something that I was taught in my very first DGS class at UConn in that many questions in genetics are answered by the simple phrase: it depends. Traits such as hitchhiker’s thumb and being able to roll your tongue may have some genetic components but environmental factors play a role as well. Students then got together to discuss traits that they believe to be polygenic, or have multiple genes involved. Ideas that they came up with were height, hair, and skin color. We also played around with the idea of multifactorial diseases and what this might mean for health issues such as hypertension or cardiovascular disease.

Scientist at work

“Students learned that features such as dimples, cleft chin, and whether your ear lobes are free or attached to your head are not considered genetic.”

We then moved into the laboratory exercise of DNA extraction. DNA extraction is the first step in many diagnostic technologies, such as PCR, next generation sequencing, and gel electrophoresis. Our young scientists were able to lyse (or break open) cells and precipitate the DNA in ethanol. As students learned, DNA is insoluble in a salt and alcohol mixture and therefore precipitated out as white stringy clumps in the center of the tube.

DNA test tube

Our session wrapped up with a talk from Dr. Jaclyn Beirne, a medical geneticist at UConn Health. She discussed with students the process of becoming a medical geneticist, which includes medical school, residency, and a fellowship program. She then went on to explain a day in the life of a geneticist by talking about a disorder she frequently sees. Phenylketonuria (PKU) is an inborn error of metabolism where a certain enzyme is functioning improperly leading to a build up of the amino acid phenylalanine. Dr. Beirne asked the students what some treatments may be for PKU, for which they had some very thoughtful and creative answers! One of the most common treatments is simply prescribing the patient a diet low in phenylalanine. In fact, Dr. Beirne encouraged students to check out the nutrition label on a bottle of Diet Coke. Diet sodas often contain sources of phenylalanine, so companies put it on their label as a warning to those with PKU.

Professor giving lecture

It was most definitely a productive session with great participation from all students! I want to thank Dr. Beirne and Sarah, a current DGS student, for taking time out of their busy schedules to spend the morning with us. Stay tuned for next week’s post after students learn about genetic testing!

Published 7/9/2019 by Kathleen Renna