Genetics 103: Questions & Answers (Hopefully)

I'm well aware of the fact that my cell looks more like an over-easy egg, but I hope this helps to clarify  the following (and last set of) questions:

1. Are neuromuscular problems genetic in origin?

Not all neuromuscular disorders are genetic, but there are many that are. Some examples of genetic neuromuscular disorders include spinal muscular atrophy and the different types of Charcot-Marie-Tooth disorder. These conditions can be a challenge to diagnose, but it is important to determine when a neuromuscular patient may have a genetic cause, as then it can impact other family members.

Answer by: Angela Filose: I work as a full-time genetic counselor for a Kaiser hospital, working with prenatal, pediatric, and hereditary cancer patients.

2. What is mitocondrial DNA, where did it come from and why is it needed? 

In humans, mitochondrial DNA spans about 16,500 DNA base pairs, representing a small fraction of the total DNA in cells. Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. It is inherited solely from your mother. Many genetic conditions are related to changes in particular mitochondrial genes.

Answer by: Anna Rossoshek, M.S., M.B.A.: I work in the Chemical Genomics Branch at NCTT/DPI. My work encompasses a broad scope of functions that allows me to utilize my education, both scientific and business management, in addition to the experience I have gained through many years as a Biologist in an NIH Intramural Lab and as a Scientific Administrative Analyst in the Division of Extramural Research at NHGRI. I currently assume the role of a Project Manager for the four main scientific sections of the branch. Those sections include Tox21, RNAi Screening, Chemistry Technology Development, and Assay Development and Screening Technology.

  

3. Can a genetic test such as whole exome sequencing detect mitocondrial disorders?

Good question! Mitochondrial diseases can be caused by mutations in either the mitochondrial genome (a small circular chromosome found within the mitochondria) or by mutations in the nuclear genome (on the chromosomes found in the nucleus). Whole exome sequencing is typically done in such a way that only the exons in the nuclear genome are captured and sequenced, and thus, will only identify some of the mutations associated with mitochondrial disease. Some labs will also do a separate analysis of the mitochondrial genome to identify those mutations.

Answer by:  Hooker, Ph.D., Sc.M.:I am the Associate Director of the Johns Hopkins Bloomberg School of Public Health/National Human Genome Research Institute Genetic Counseling Training Program and a contracted staff scientist within the Social and Behavioral Research Branch of the NHGRI. Prior to entering the field of genetic counseling, I completed my Ph.D. in Molecular, Cellular and Developmental Biology.

4. Do you see the whole exome sequencing test being available to the general public and covered by insurance companies any time soon?

Great question. I don't see this happening in the very near future, but I do see the possibility for public access to whole exome sequencing becoming a reality in the next 20-30 years. It may still be too expensive for many at that point, but also available to many. 

Your question about whether insurance companies would actually pay for this testing is complicated. I think we would have to prove that whole exome testing would be useful to our medical providers. That is something I think will take much longer than 20 years. Genetics is complicated by the fact that our technilogical advances, our ability to see information, is improving much faster than our ability to understand that information. 

That takes much more work since we are talking about how our genetics affect our body's functioning, and our bodies are very complex. We also have to take into account how our bodies are affected by the environment we live in. Lastly, we need to understand the social and ethical implications of being able to get this information. Is it something, as a society, that we want the general public to have access to? There are many of these discussions going on and many more that need to happen as we develop these technological abilities. 

Answer by: Ami Rosen: For the past 10 years I've provided genetic counseling to people at risk for developing Huntington's Disease. I am also a neurogenetics research coordinator, well-versed in the ethical concerns of human subjects research and DNA banking. 

5. Do you see things such as "genetic discrimination" happening in the near future?

They are definitely possible, so that's why it's important that we take measure now to prevent them through legislation, promoting awareness, and developing guidelines for the professionals involved. Right now, individuals are protected by GINA (Genetic Information Non-discrimination Act), where health insurance companies cannot discriminate someone based on his/her genetic testing results. In the future, we may also move towards establishing legislative protection from genetic discrimination from other sources, like disability insurance, life insurance, etc. 

Answer by: Julia Su: I am a second year genetic counseling student from Sarah Lawrence College (graduate May 2012). I have rotated through several genetics clinics in the New York area and Toronto. I am highly passionate about genetics, as well as the integration of psychosocial counseling in clinical genetics services.

6. Is the structure of the DNA molecule something that was originated randomly? or was it designed? 

The structure of DNA (the double-helix) is the way it is out of necessity. This structure, which resembles a twisted ladder, makes it possible for each DNA strand to be precisely copied. These copies, which contain the same genetic information as the original DNA strand, can then be passed along to an organism's offspring. I'm not sure when DNA first evolved into its double-helix structure. Sounds like a chicken-and-egg problem!

Answer by: Becky Clark: I am a genetic counselor and research associate in an ophthalmic genetics department. I counsel patients on inherited retinal disorders and manage a repository and database for genetic testing research. 

I wasn't too happy with the last response, but in all fairness, that is a whole other debate worthy of it's own chat session. I really believe that I answered my own question better in this post: Fearfully and Wonderfully made.

With that said, I'm very grateful for the opportunity to chat with the experts in the subject because it did help me get some more understanding over the things that happened to us, it had a great therapeutic value for me, I hope that it has the same value for you, if you stumbled upon this post.

Genetics 102: Questions and Answers (Hopefully)

This are some more questions and answers, I decided to chop it into smaller bites since all this information can become a little overwhelming. (At least it felt that way for me.)
Also, if you're new to the whole thing, I did find from our experience that there are different types of genetic tests available, looking at different pieces of information, this are the ones that we had done:

1. FISH test: A preliminary test that looks into the most common pairs of chromosomes that present problems: 13, 18, 21, X,Y.
2. Amniocentesis: Test used to verify that there are indeed 23 pairs of chromosomes. 22 autosome pairs that are the same for males and females, and the 23rd pair which determines the sex. XX for female and XY for male.
3. Microarray: Zoomed in look at the chromosomes. Able to find more rare genetic conditions.
4. Whole Exome Sequencing: When all else fails and you still have no answers. Very expensive, not covered by private insurance yet. We didn't get to run this test for our boy.

Hope this preliminary info brings some background to the following questions:

1. What are the top 5 most common myths of genetics?

What a fun question! Off the top of my head, I'd say: 1. Genes can skip generations. 2. Having the same blood type as your spouse will cause birth defects 3. Scientists can know everything about you by looking at your DNA. 4. Red heads are going to go away due to evolution. 5. Genetic counselors will tell expectant parents whether or not to keep their baby.

Answer by: Diane Masser-Frye: I work at a Children's Hospital with families of children with genetic conditions. I also consult with an agency that provides services to people of all ages with developmental disabilities. My role is to help these individuals and families understand the role of genetics in their families and how their conditions are inherited.

2. I understand that the nucleus of the cell contains the DNA molecule. How do you jump from there to genes and chromosomes? 

Genes are contained within DNA. So, they are in the nucleus, too. Chromosomes are the forms that DNA take during certain times in the cell cycle.

Answer by: Kris Wetterstrand, M.S.: I work in the NHGRI Office of the Director as the Scientific Liaison to the Director for Extramural Activities. I have over ten years experience managing the NHGRI grant portfolio, having participated in the Large-scale Sequencing Program, which managed the Human Genome Project, and the Human Microbiome Project, an effort to sequence the DNA of microbes (e.g. bacteria) that live in and on humans and the ENCODE Project, an effort to identify functional DNA elements in the human genome. My background is in population genetics and molecular evolution.

3. Are all disorders developed because of problems with a person's chromosomes?

Not all disorders are because of chromosome problems. Some disorders are because there are too many or not enough copies of a whole chromosome, like Down syndrome. Some disorders are due to a change to a single gene located on a chromosome. But most diseases are complex, and have a number of factors that work together to cause the disease. Some of these factors are genetic, but many have to do with a person's environment and behaviors, like diet and exercise.

Answer by: Rachel Shapira: I am studying genetic counseling at the Johns Hopkins School of Public Health and the National Human Genome Research Institute. I am currently in a clinical rotation at the Walter Reed National Military Medical Center Prenatal Assessment Center.

4. What does the Microarray test looks into? Is it at specific genes? or chromosomes?

DNA microarrays can give us a "zoomed in" look at chromosomes allowing us to see genetic deletions or insertions that can't be seen just by looking at chromosomes under a microscope. The amount of information that can be obtained by a microarray varies depending on the type of array and some are capable of picking up very small deletions or insertions in the genome.

Answer by: Gillian Hooker, Ph.D., Sc.M.: I am the Associate Director of the Johns Hopkins Bloomberg School of Public Health/National Human Genome Research Institute Genetic Counseling Training Program and a contracted staff scientist within the Social and Behavioral Research Branch of the NHGRI. Prior to entering the field of genetic counseling, I completed my Ph.D. in Molecular, Cellular and Developmental Biology.

5. Does the Microarray test look into all the chromosome pairs?

It can. Scientists can set up a microarray to include all of a genome (all the chromosomes) or just parts of the genome (some of the chromosomes). It depends on what scientists interesting in studying.

Answer by: Kris Wetterstrand, M.S.: I work in the NHGRI Office of the Director as the Scientific Liaison to the Director for Extramural Activities. I have over ten years experience managing the NHGRI grant portfolio, having participated in the Large-scale Sequencing Program, which managed the Human Genome Project, and the Human Microbiome Project, an effort to sequence the DNA of microbes (e.g. bacteria) that live in and on humans and the ENCODE Project, an effort to identify functional DNA elements in the human genome. My background is in population genetics and molecular evolution.

6. Does a normal Microarray result mean that a person does not have a genetic syndrome?

Definitely not. A normal microarray result means there are no obvious (a few thousand bases or more) missing or deleted pieces of the genome. A person can have a genetic syndrome with just one single base substitution, which is not detected using microarray testing.

Answer by: Toni Pollin: I have a background in both genetic counseling and human genetics. I study the role of genetic factors in complex diseases, particularly diabetes and dyslipidemia, and the interaction of genetic with lifestyle and environmental factors. I also co-lead a human genetics PhD program and teach graduate, genetic counseling and medical students.

7. I know more and more about laboratories doing the whole exome sequencing. The question is, is there a benefit of sequencing the whole exome? Knowing that you might get a lot of variants of unknown significance. How do you report to the patient in that case? Sorry, we found something that we have no clue what it is, though you still have to pay thousands of dollars?

This is a fantastic question. Whole exome sequencing is new technology with great promise. We are still learning a lot about how to best use the information gained from exome sequencing to improve medical care. 

Many of the early patient exome sequences have been generated in hopes of identifying the genetic cause of a specific disease, to better guide treatment. Within these sequences, we are also finding variants which are already known to have important implications for other medical conditions in the patients and, potentially, in their family members. Over time, we expect to be better able to predict the significance of different variants, and have fewer "variants of uncertain significance."

Answer by: Gillian Hooker, Ph.D., Sc.M.: I am the Associate Director of the Johns Hopkins Bloomberg School of Public Health/National Human Genome Research Institute Genetic Counseling Training Program and a contracted staff scientist within the Social and Behavioral Research Branch of the NHGRI. Prior to entering the field of genetic counseling, I completed my Ph.D. in Molecular, Cellular and Developmental Biology.

8. How is a gene actually identified within a DNA sequence? is it by matching the entire sequence against it's expected pattern? Or is it also required to be located at a specific position within the sequence?

Genes are identified by matching the DNA sequence against its expected pattern, which means the pattern as well as the specific position within the sequence match.

Answer by: Dana Petry: I am a second-year genetic counseling student in the Johns Hopkins University/NHGRI Genetic Counseling Training Program. I am taking classes in genetics, public health, and psychosocial counseling. I have also rotated through various clinics for prenatal, pediatric, and cancer genetic counseling.

 8. What is the difference between the incidence of something and the prevalence of something?

Excellent point to clarify, as these are often used interchangeably. Incidence tells us about a change in status from non-disease to disease, thus being limited to new cases. Prevalence includes both new cases and those who contracted the disease in the past and are still surviving. In genetics, we usually discuss incidence as the birth rate for a given condition (1 in 50,000 births, for example) and prevalence for the number of affected individuals in a given region (US vs world, for example). 

Answer by: Julie Rousseau: Following many years in clinical genetic counseling, the majority of which was spent in pediatric genetics, I currently work in a laboratory setting. In this position, I interpret DNA results and help providers determine which test(s) are most appropriate for their patients.

More Q&A to come,

Genetics 101: Questions and Answers (Hopefully)

There's a day for everything, and last April 20Th  was DNA'S day, in which there was an open chat with all the geneticists, microbiologists and people involved in the Human Genome Project. (mind you that their minimum level of education was a PhD.) They were answering questions for the everyday street walker like me, with no more prior knowledge of the cell division than a model of play-doh made in the fourth grade, and a biology class in middle school were I probably was doing more important things like writing a love letter to whoever was my crush at that time. Darn it!

I did jump in the chat with my list of questions, at least the ones that would get a shot at being answered on this side of heaven, I hope and pray that this post reaches someone walking a similar path, because at my times of Goggling myself to death I wish that there had been such a post when I was new to the whole thing. Without more ado, this were the questions and answers from the chat. Most of the questions were mine, but some others were from other fellow chatters, and I though that they were worth the copy-pasting. Unfortunately, I cannot give the credit were is due, since some questions were anonymous, please understand. 

1. When a baby is born with a genetic syndrome, is there anything that one of the parents could have done different to prevent that? 

No, when a baby is born with a genetic syndrome there is not anything a parent could have done differently. 

Answer by: Kelly Donahue. Prenatal genetic counselor. I speak with families that are at risk to have children with genetic conditions. This risk may be based on their family history or be signaled by results of specific blood work or ultrasound during their pregnancy.

2. What are three things that every human should understand about DNA?

In my opinion: 1) DNA is the "blueprint" necessary for life 2) it transmits hereditary information from generation to generation 3) it controls the production of proteins.

Answer by: Sandy Woo: I work with patients and their families who either have a genetic condition or birth defect, are at risk for one or have a risk to have a child with such. I provide education, facilitate genetic testing decisions and psycho-social support.

3. What can DNA tell us about a person? 

That's a good question. Something like 99.9% of our DNA is the same no matter the person. The remaining DNA that's different makes us who we are compared to any other person. 

We also have mutations which alter the protein products of any given gene, and these are what we spend a lot of time and money researching. That's because many diseases either have a single gene mutation that causes them or different mutations that predispose one to certain diseases.

 A genome is the totality of all of our DNA spread over our 46 chromosomes. In the past, if we looked at an entire genome we wouldn't be able to tell much about the person. But now we're getting to the point scientifically that we can analyze an entire person's genome for a relatively low cost and in a shorter period of time. It won't be long that it will be very cheap to scan an entire genome to know every disease risk someone has, but we're not there quite yet. This is where most of science is focused, but note that DNA doesn't tell us many important things about a person, such as their character, values, or insights on life. Those traits are all influenced by genes, but are something DNA analysis will never be able to completely tell us.

Answer by: Ian Wallace: I am a clinical genetic counselor who recently launched a new genetics clinic in a rural area. I see patients for any genetic indication, to include prenatal, pediatric, adult, cancer referrals.

 

4. What are all the things that happen when the cell divides? 

Cell division is a complicated process. Let's think about mitosis, which is where one cell basically replicates itself, so you end up with two identical cells. 

What needs to happen is all of the structures of that starting cell needs to be copied. For example, all of the chromosomes need to be doubled and then halved into each ultimate cell. 

If you remember the process of mitosis, that's where the cell goes through prophase, metaphase, anaphase, and then telophase. The chromosomes become solid, they line up in the middle of the cell in an orderly fashion, and then structures on each end of the cell "pull" the right number of chromosomes to each new cell. And that doesn't even address what happens with the other cell organelles!

Answer by: Angela Filose: I work as a full-time genetic counselor for a Kaiser hospital, working with prenatal, pediatric, and hereditary cancer patients.

 

5. If a "mistake" were to happen, what happens to the DNA that was copied wrong? 

When DNA is being copied, there are different possible outcomes if there is a mistake. The cell actually has a few "proofreading" mechanisms to help fix some errors. For example, there is a group of proteins called "mismatch repair" enzymes, which helps to correct an error where the wrong base pairs are put together (like a G to a T, rather than a G to a C). So in some cases, the cell can correct the error.

Other times, an error like a deletion, a duplication, or a point mutation within a stretch of DNA might happen, and this could be missed. This might be an example where a permanent mutation could then continue with that gene, and possibly could change the function of that gene. 

Answer by: Angela Filose.

More Q&A to come, 

Image from : http://meship.com/Blog/2011/07/27/dna-sent-to-the-cloud/

Me time?

Finally some peace and quiet, really some peace and quiet with really nothing to do. I mean, my TO DO list is miles long, but there's really nothing that should o r could be done today. So here I'm catching up with my blog, liking other people's toenails on Facebook and liking the fact that they will be eating enchiladas for dinner, and with my new addiction: "So You Think You Can Dance." Finally, I said it out loud! I'm addicted!

It's weird because it seems that it's the first day in a long time that I don't have to make follow up phone calls: To follow up on Zach's Medicaid application (still in in the fight) , to follow up with some left over denied claims, to follow up with my Obgyn, to follow up with the cemetery to get Zach's stone, to call back that person that helped me in my times on need to say thanks,... I just don't HAVE to do that. Not today. I refuse to do that today.

Today is for me, and I refuse to let guilt take over and steal that freedom away from me. Since lately every time that I get to feel some happiness, guilt comes crawling around in silence until it takes over. I lost my child, therefore I should be sad and crying all the time. Right? Right? How come that I get to feel and experience happiness every now and then? It doesn't seem like I deserve that.

I've read that this a common feeling during the grieving process. I still miss and cry for my son EVERYDAY, but I've managed to do it on a schedule. I cry from 8:00 am to 8:45 am in my car, or in the parking lot before work, and I cry in the way back as I sing out loud every song that Pandora has to offer, and I firmly believe that each song has been custom made and written for my boy. I will count that as progress even though, the trips to the grocery store are still a kick in the butt. Yes, thank God I can buy groceries, and we always have food, but in comparison with other mom's out there, my shopping cart will always be empty. Or at least that's what it seems like for now. I have developed a serious issue with the whole grocery store scene: happy mom with baby in the cart doing some carefree shopping. Why something that seems so ordinary is like one of my ultimate life goals, and why is this something that seems as unreachable to me as getting the Nobel price?

O well, I will pray and see what unfolds, one day at a time.
 In the meantime, I NEED to know who are the Top 20 on So you think you can dance.

Zach's Garden: The making of...

It really helped to have the most beautiful helpers!

People that knows me well knows that I'm not a patient person, by any stretch of the imagination! But life has stretched my patience quite a bit; our hopes had been crashed, our hearts have been broken and our pride and sense of entitlement has been shattered in tiny small pieces...

But there is hope and growth in that, Zachary taught me among many other things, not to take anything for granted, and for that I will be forever grateful.

It was our neighbors idea to make a garden in honor of him. It all began when we came back from the funeral home exhausted and brokenhearted, they came to our door and we learned that  their close family in Chicago had lost an infant son to SIDS, about 20 years ago. They wanted to give us a garden for our boy, so we could see that garden grow and thrive just as we would've seen our boy. They also had a book with Texas landscaping, that included plants that could take this merciless heat, and we were told: You guys just choose what you want to do, the spot and we will make it happen.

I just can't believe that we have this amazing people in our lives! And well, they made it happen.

The garden has been up for about two weeks. Yes, and I'm just posting about it now since I have a talent to procrastinate.  Surprisingly our dog Hunter has been pretty gentle and careful with our little garden and hasn't chewed up the flowers or dug any holes yet. But I'm not taking chances, I will get it fenced soon. But who knows what soon means, given that I'm the procrastinator that I'm, so we shall see.



I have a new ritual now, having my morning coffee in the garden and talking to my boy. I also pray, and I talk to my son out loud, even if it sounds crazy. I know that right now he's probably busy pulling Jesus beard and having a blast in heaven, but  I believe that he still hears me. What do you think? Do you think that he can see us down here? I just hope that he likes his little garden.