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Should You Get Non-Invasive Prenatal Testing?

If you are a pregnant woman reading this, you are probably thinking that another ‘piece of advice’ about what you should and should not do, know, think, or feel is the last thing you need right now. After all, what you want to do is enjoy the glows and highs of being pregnant.

However, knowing about Non-Invasive Prenatal Testing (NIPT) may be one of the more responsible things to do at the beginning of your pregnancy. How terrible can it be? Given that pieces of your baby’s DNA circulate in your very own bloodstream, all you have to do is give blood, and doctors can find out about possible genetic issues of your baby pretty quickly and reliably. So, should you do it? Before saying either aye or nay, read some of the things below that may shed some light on the details and then decide for yourself. After all, like many other choices you make as a mom,this is immensely personal and intimate.

Let’s begin by underlining that a non-invasive prenatal test is considered a prenatal screening method. This means that it takes into consideration the cell-free fetal DNA from your baby’s placenta in a sample of your own blood in order to figure out whether you are at an increased risk of giving birth to a child that has a genetic disorder. In other words, a screening such as NIPT will not tell you for sure whether you will or will not give birth to a child with a chromosomal disorder. Rather, you will find out the likelihood of having that be the situation. So, now you may think what good is this? I find out about the chance of something being wrong with my baby. All it will do is worry me for the next eight months or so. Yes, you may be right. However, despite the fact that NIPT cannot tell you for sure what is going on with the genes of your baby, it is incredibly accurate. In fact, it can tell you the likelihood for three of the most common conditions (see below) with a whopping 97 to 99 percent accuracy.

Philosophically speaking, with such an accuracy, can’t a screening be called a test, you may wonder. That’s an interesting question. But before going further into the philosophy of why scientists call things certain ways, let’s continue going in the NIPT direction some more.

Once the results of NIPT are in, your physician and you can make more informed or educated decisions together. These include whether or not to do further, typically more invasive, diagnostic testing such as chorionic villus sampling or amniocentesis. These tests collect the amniotic fluid or placenta, and as such are based on the DNA of the baby. Now, these tests are TESTS. They can tell you for sure (100% certainty) whether or not your baby has that chromosome abnormality that the NIPT procedures suggested. When it comes to these last two tests, however, you’ll have to take the good with the bad: they are invasive (think poking your belly to get to some of the sampling material) and that means that they might increase your chances of losing your baby (having a miscarriage).

NIPT Testing Procedure

NIPT Testing Procedure

All you have to do is offer your arm at the physician’s office for a blood drawing. Your blood is then sent to a lab where technicians will analyze the cell-free DNA for signs of abnormalities. After you have received your results, your gynecologist will most likely want to pair the findings with additional ultrasound or nuchal translucency screening in order to decide whether or not you need more testing. It is recommended that a positive NIPT is almost always confirmed with either chorionic villus sampling or amniocenteses. These can concurrently also look for additional problems that the NIPTs cannot detect.

In addition to being able to pick up the baby’s blood type as well as gender, the NIPTs screen for three of the most common chromosomal disorders, including Trisomy 21 (Down Syndrome), Trisomy 18 (Edwards Syndrome) and Trisomy 13 (Patau Syndrome).

Different Kinds of NIPTs

There are currently four companies on the market that offer prenatal testing. These are Genesis Serenity, Harmony, Natera,and MaterniT21. They are essentially all the same. There are slight differences among the panels of genetic diseases that they screen for. For example, not all of them will screen for abnormalities such as triploidy and microdeletions. Furthermore, not all of them look at fetal cell-free DNA (some only consider the cell-free DNA from the mother), which means that they do differ when it comes to the accuracy of things. It would be best to consult with your gynecologist in regards to which of the four they prefer and stick to that.

When Is NIPT Done?

The benefit of the screening is that it can be done earlier than any other prenatal screening or diagnostic test. This means that it can be done any time after nine weeks into a pregnancy, which is pretty early. Just to compare, all other standard screenings are done later. Nuchal translucency is done between weeks 11 and 13, chorionic villus sampling is done at 10 to 13 weeks, the time range for amniocentesis is between weeks 16 and 18 and that for a quad screen is between weeks 14 and 22.

So, who Is NIPT for, really?

The American Congress of Obstetricians and Gynecologists still deem that NIPT needs additional evaluation in order to be considered ‘standard screening’ despite their accuracy and low rate of false alarms. However, the Congress does advise that all women discuss possible screening options with their doctors. This is different to what has been advised so far, namely that only women older than 35 and those with genetic disorders in their past (either among their children or among their family) get tested.

Given all this, there is no clear yes or no answer to whether or not you should get NIPT simply because the choice is deeply personal and intimate. However, whatever your preference may be, it certainly doesn’t hurt to know your options.

Marfan Syndrome Test, Symptoms, Genetic Causes, and Life Expectancy

What do Sergei Rachmaninov and Niccolo Paganini have in common? At first, you may think it is their musical genius—and you are right. However, I bet you had no idea that both had a condition called Marfan Syndrome (more on that below). Rachmaninov is considered a genius in the field of music. The composer and pianist had an extraordinary long reach on the piano thanks to his long and flexible fingers and this thanks to Marfan Syndrome. He was also very tall with a slender and long nose. Along similar lines, Paganini was also considered a musical genius for his talents with the violin. His ‘abnormal’ reach of three octaves on the violin earned him the title of most distinguished violinist of all times. His ‘talent,’ however, just as with Rachmaninov, was also attributed to Marfan Syndrome. As an aside, Paganini lived 100 years before Rachmaninov and his works were sources of inspiration for the pianist and composer.

So, what is Marfan Syndrome?

Well, as much as it may seem as such, it is not a condition of musicians. Apparently, Julius Caesar also had it and it is rumored that Michael Phelps may have it, too. Marfan Syndrome is a genetic disorder that essentially affects the thread that holds it all together in the human body: connective tissue. It is considered the cement that holds the body in place and every organ in the body possesses it. Even blood is considered connective tissue. Fundamentally, the task of connective tissue is to bind things together, as the name implies. It binds parts of an organ, blood vessel or joint together. Connective tissue is made up of many proteins. What bites the dust in Marfan Syndrome is Fibrillin, of the constituent fibers of connective tissue. In people with defective Fibrillin, that is manifested as being taller than the rest, having longer arms, legs and flat feet as well as joints that are more flexible than usual. Even though this may seem like an advantage at first, make no mistake. Those who suffer from it grow to have health problems in old age. As connective tissue is found everywhere in the body, these medical problems tend to affect joints, the heart and lungs,and eyes, to name a few. Some Marfan Syndrome features can be life-threatening. These include enlargement of the main blood vessel that carries blood from the heart to the rest of the body. Interestingly, however, Marfan Syndrome does not affect intelligence.

Genetic Causes

An estimated 1 in 5,000 people have Marfan Syndrome. This includes both men and women of all racial and ethnic backgrounds. An approximate 75% of affected individuals inherit the condition. This means they get it from a parent who has it. However, the syndrome can also affect an individual spontaneously, meaning it happens with no heritable family history. There is an overall 50% chance that an affected individual will pass on his or her genetic mutation to their offspring.

Marfan Syndrome is caused by a mutation in the gene that communicates to the body how to make Fibrillin. This mutation, in turn, somehow results in an increased production of a protein called transforming growth factor beta, or TGF-B. This increase causes problems with connective tissue, and this is manifested in symptoms of Marfan Syndrome.

Genetic Testing

Genetic Testing

Getting genetic tested is important. This is particularly important as features of the disorder are not always present right away, even if people with the syndrome are born with it. Some people have symptoms right away, and yet others develop these symptoms later on in life. This means that testing and obtaining accurate, early diagnosis and treatment can improve life expectancy and even save lives.

Furthermore, Marfan Syndrome symptoms vary from individual to individual, which is why physicians won’t always diagnose it right away without a proper family genetic background as well as a few other tests. If Marfan Syndrome is suspected, doctors will perform heart tests such as an echocardiogram, a CT scan or an MRI. Furthermore, doctors will want to look at the eyes by doing eye tests such as a slit-lamp exam (looking for lens dislocation, cataracts or a detached retina) or an eye pressure test (looking for glaucoma). Given that Marfan Syndrome is a genetic disorder, genetic testing may also be ordered in order to be completely sure about the diagnosis.

Treatment

Depending on the diagnosis, treatment includes anything that focuses on where connective tissue problems have manifested themselves. This includes surgeries such as aortic repair to compensate for aortic enlargement, scoliosis treatment in the form of back braces (for children until their growth is complete), breastbone corrections in the case of a sunken or protruding breastbone as well as eye surgeries to compensate for torn or loose retinas or cataracts.

Life Expectancy

Obtaining early and accurate test results, as well as proper treatment, may help reduce symptoms that would otherwise be life-threatening. This, of course, improves the life expectancy of those who are affected. Given all that, individuals with Marfan Syndrome do live to old age. Certain adjustments have to be made, of course, such as avoiding intense sports as connective tissue may not be able to provide the support that is needed. Furthermore, individuals can also suffer emotionally knowing that they may not be able to live fulfilling lives or that they may pass Marfan Syndrome to their children. This is why it is very important that those who are affected receive emotional support.

Marfan Syndrome, however, is interesting if we go back to Rachmaninov and Paganini. Isn’t a disorder supposed to slow someone down and make him more prone to fatigue and/or weakness? Both pursued their dreams despite their conditions. As such, they truly embody what we have heard so many times, “When there’s a will, there’s a way.”

Microarray Test: What You Need to Know before Ordering Chromosomal Microarray

So, your doctor or genetic counselor has advised you to have a chromosomal microarray test done. Chromosomal microarray is a mouthful and you are probably wondering what it actually is and perhaps even whether it hurts or not.

We have all heard that famous “it’s all in your genes” statement, implying that most of who we are is found within our genes and DNA. Taking this statement further, our genes are found on chromosomes, and we can find out a lot about what illnesses we have or might have based on the analysis of our chromosomes, also called karyotyping. So that is the “chromosomal” part of the chromosomal microarray mouthful. What about microarray? Taken literally, ‘micro’ means very small, while ‘array’ simply means an ordered series or arrangement. Taken together and placed in the context of biology, microarray is essentially a very small arrangement of genetic material on a chip.

Perhaps you are now even more confused, wondering how all of that information fits into your story of needing a chromosomal microarray. Let’s back up a little and bring it all back together a few sentences later.

For several reasons, it is of utmost importance to figure out what is beneath an individual’s intellectual challenges and/or congenital anomalies. These reasons include counseling (perhaps you are in the middle of family planning and need prenatal testing in order to know your prognosis), or you need access to appropriate resources or you simply need to put your mind at ease with knowing what lies ahead. A chromosomal microarray, being a high-resolution genetic test, looks at very small gains and losses of genetic material within the genomic information of an individual. It can help figure out things such as isolated spectrum disorder as well as other findings, isolated developmental delay or intellectual disability, several congenital abnormalities when there is no syndrome diagnosis as well as unusual physical features. Given all this, that still begs the question of what a chromosomal microarray really is.

Fundamentally, the chromosomal microarray technology is used to figure out if there are any abnormalities within an individual’s pool of genes. These abnormalities, or mutations, often manifest themselves as either small extra or missing pieces of genetic information. In the laboratory, these gains and losses are called copy number variants (CNVs). These have varying effects on individuals. They can either be of no consequence at all, they can result in physical and/or intellectual consequences or they can be protective against a disease as in the case of HIV.

At the heart of the microarray technology is a small glass slide that houses thousands of genes in an array, or in an ordered fashion (see definition above). That glass slide is then washed with DNA probes that are labeled with either green or red probes. The patient’s DNA is labeled with green probes while the control/reference probes are red. Two colors are used to visualize the CNVs (gains and losses) in a much higher resolution. In a normal (or healthy) scenario, each probe should attach (or hybridize) to the test (green) as well as control (red) DNA, which will result in a yellow signal. Therefore, if there are any extra pieces of DNA, implying extra genetic material or an abnormality, that will produce a green signal. Similarly, missing DNA (or the lack of genetic material) will produce a red signal on the readout. Each glass slide is scanned and image analyzed via computer.

How is the test done?

How is the test done

First of all, it is important to know that there are four types of testing programs. These include newborn screening, carrier testing, prenatal testing (genetic test) and presymptomatic (predictive) testing.

The chromosomal microarray is done very similarly to all other genetic tests. All that is needed is a patient’s DNA, which can be extracted from materials such as saliva or blood. Either the patient’s doctor or the patient themselves (following a referral) order a test kit from any company that offers chromosomal microarray analysis testing. Once the kit arrives, patients can either submit their sampling materials themselves or have their blood drawn at their doctor’s office. Once the respective laboratories receive the patient’s materials, DNA is extracted and then hybridized to the microchips of DNA (see above.).

What do the results mean?

An ordering physician, as well as a genetic counselor, are trained to discuss the results of a chromosomal microarray test, which is why it is important to consult with them prior to making specific conclusions. In a normal scenario, micro-deletions/micro-duplications are excluded. However, this does not rule out a disorder that is caused by a mutation within a single gene. It is recommended that further genetic consultations should be done in order to find out if more genetic testing should be done.

If a pathogenic micro-deletion or micro-duplication is found after a chromosomal microarray, it can be identified based on the previously described disorder. Also, depending on what has been found, it may warrant further parental testing and/or additional medical testing.

Lastly, if a variation has been found that has an unclear clinical significance, it is important to know that now every CNV in the genome leads to disease. In this situation, it is important to have parental samples and information in order to conduct additional genetic testing and find out if, at least, the CNV is familial and, therefore, less likely to be pathogenic.

Chromosomal microarrays are also offered to pregnant women following an irregular ultrasound that may point to a genetic abnormality of the fetus. In that situation, the baby’s DNA is analyzed to look for possible genetic reasons behind the ultrasound indications. Typically, a prenatal test requires a sampling of the amniotic fluid while only a buccal swab is needed for a postnatal test. Following submission of the specimen or material, laboratory procedures are pretty much the same as described above.

MMA Disease: Brief Overview of Methylmalonic Acidemia

Let’s start simply.

In order for our body to benefit from the proteins we eat, it has to be broken down into smaller parts called amino acids. There are special enzymes that edit or make changes to those amino acids so that the body can benefit from or use them. Along the same lines, fat from the food we ingest has to be broken down by enzymes into substances called fatty acids that the body uses for energy. MMA is a condition in which the aforementioned processes are disturbed because a particular enzyme is not working properlyas a result of mutations (see below). This prevents the correct use of certain amino acids and fatty acids which causes a build-up of toxic substances in the body—this leads to health problems.

Scientifically speaking, MMA stands for Methylmalonic Acidemia, and in many ways, it can be considered a kind of umbrella term for the many different forms that it represents. MMA is caused by several things, including cobalamin (or vitamin B12) disorders as well as MUT deficiencies. For example, those who are affected by MMA caused by cobalamin A deficiencies have trouble making cobalamin enzyme A. All cobalamin enzymes are important so that the body can break down certain foods (more details below). Furthermore, some forms of MMA can be treated with vitamin B12 injections. They are termed ‘vitamin B12 responsive’ and they are cobalamin A and cobalamin B deficiencies. On the other hand, vitamin B12 non-responsive types cannot be treated with vitamin B12 deficiencies.

Overall, MMA is aninherited condition that is also considered an organic acid condition as it can culminate in a toxic amount of organic acids in the body. It is marked by the body’s lack of ability to break down certain fats and proteins. An estimated one out of every 50,000 to 100,000 babies born in the United States is affected MMA. Early signs of the disease include sleeping longer or more frequently, fever, trouble breathing, vomiting, weak muscle tone, increased bleeding and bruising as well as an increased number of illnesses and infections.

Genetics

While mutations in several genes can cause MMA (MUT, MMAA, MMAB, MMADHC and MCEE), an estimated 60 percent are caused by mutations in the MUT gene. Furthermore, long-term effects of the disease are largely dependent on which gene is mutated as well as to what extent. The MUT gene is responsible for directing the production of an enzyme with an extremely complicated name, methylmalonyl CoA mutase. It collaborates with vitamin B12 in order to break down several amino acids, certain lipids as well as cholesterol. Essentially, mutations in the MUT gene change the structure of the enzyme that it is responsible for. These mutations also lower the amount of enzyme that is produced, and all that hinders these molecules from being broken down properly. All of this then causes accumulation of the substance methylmalonyl CoA as well as other possibly toxic compounds in organs and tissues. Ultimately, this results in symptoms of MMA.

Furthermore, the MMA cases that are caused by mutations in all the aforementioned genes are caused via the same mechanisms, namely impairment of methylmalonyl CoA mutase. That’s a mouthful, I know. Suffice it to say that there are several genes that affect the production of methylmalonyl CoA mutase, which causes difficulties in the breaking down of fats and lipids, which is a problem.

Genetically speaking, MMA is an autosomal recessive disorder. This means that it is present on an autosome, or on a non-sex chromosome (remember that humans have 23 pairs, 22 autosomes, and either an X or a Y chromosome). Recessive means that a baby must have inherited two copies of the mutation in order to have MMA. Most often, parents of a child with MMA each have one copy of the mutation without actually having any symptoms.

Genetic Testing

Given that MMA is a genetic disease

Given that MMA is a genetic disease, genetic or DNA testing is available for patients to test for the mutations that are known to cause the disease. Genetic testing essentially looks for changes in the genes that cause MMA. While not completely necessary for a diagnosis, it can be helpful during prenatal testing. For example, if both parents find out they are carriers of the mutation, it is advised they speak with a physician or genetic counselor to discuss their options.

Treatment

Patients, especially babies, who have MMA are typically treated by a doctor as well as a dietician. As with many conditions, the earlier they are detected, the better the chances are in terms of life expectancy as well as success. Children that have vitamin B12 responsive MMA are put on a vitamin B12 regimen together with a low-protein diet as well as a special medical formula. Furthermore, going a long time without food should be avoided so that a metabolic crisis is averted. Eating schedules are created together with a doctor.

Also, regular urine tests are advised so that ketone levels can be tracked. When body fat is broken down for energy, ketones are formed, which is why tracking their levels is a good way of monitoring fat breakdown. Regular blood tests are done so that amino acid concentrations are kept track of. Furthermore, being proactive about monitoring other illnesses in children with MMA can be considered a kind of treatment as that prevents worsening of the condition. Ultimately, some MMA kids may need organ transplants. In particular, liver or kidney transplants are done most frequently because that reduces some of the symptoms. However, organ transplants, particularly in kids, come with their own risks so doctors should be consulted if this is the only option.

Overall, MMA can be considered a rare disease, given its frequency. However, it can be debilitating if not treated properly, which is why remaining informed is important and could save as well as improve lives.

Factor V Leiden Test: Why Is This Test Important

Some of us may have heard of Factor V Leiden and know what this is all about. On the other hand, others may not be so sure. If you are among those who know what this is, keep reading for the amusement factor. However, if you are among those who think that Factor V Leiden is a pianist from the 19th century, keep reading. You need to know better!

Perhaps the best approach to talk about the Factor V Leiden Test and its importance is from the very basics. Let’s start with thrombophilia and build from there.

What is thrombophilia?

Thrombophilia is defined as an increased tendency to form abnormal blood clots that can block blood vessels. Think of it this way: people with thrombophilia have thicker blood than your average person that can clot much easier. A blood clot is actually the body’s repair mechanism to repair damage to either an artery or a vein. It is an accumulation of platelets (tiny blood cells) in the blood to stop bleeding. However, a clot is a blockage of the blood flow in the body and that is not a good thing. So, while blood clots are inherently protective, the outcome is negative and even painful. Thrombophilia is a genetic disorder that is caused by a mutation, which is where Factor V Leiden comes into play.

Factor V Leiden

Factor V Leiden is the name of a specific gene mutation that causes thrombophilia. It is also the most common inherited form of thrombophilia. Anywhere from 3% to 8% of Europeans have one copy of the mutation and an estimated one in every 5,000 people have two copies. People who have the mutation are at a much higher risk of developing a specific type of blood clot called deep venous thrombosis that most frequently occur in the legs. However, they are known to occur in other parts of the body such as the brain, eyes, liver as well as kidneys. This type of thrombophilia that is associated with Factor V Leiden is especially cruel as increases the chances that the clots will come loose from their original site and travel through the bloodstream from where they can get stuck in the lungs. This is also referred to as pulmonary embolism. This all sounds very horrifying, I know. However, not everyone with the mutation actually develops blood clots. Even though they are at a higher risk of developing clots, only 10% of those with the mutation go on to develop abnormal clots. Most probably the biggest issue with this mutation is among pregnant women (see below).

Genetics and Other Factors

Factor V Leiden thrombophilia is caused by a mutation in the F5 gene that is responsible for making a protein called coagulation factor V. Coagulation factor V is a protagonist in the coagulation system, which is the savior mechanism responsible for forming blood clots in response to injury. The mutation is recessive, which means that two copies are necessary for a person to actually suffer from Factor V Leiden thrombophilia.

In addition to genetics, lifestyle is a big issue when it comes to Factor V Leiden thrombophilia. Obesity, increasing age, injury, smoking, surgery, pregnancy as well as oral contraceptives and hormone replacement therapy are all factors that have all been associated with higher risks of this kind of thrombophilia.

Factor V Leiden and Pregnancy

Factor V Leiden and Pregnancy

The Factor V Leiden mutation is associated with the risk of miscarriage. In fact, pregnant women who have this mutation are about two to three times more likely to suffer multiple miscarriages or pregnancy loss during the second or third trimester. As if that is not bad enough, several studies have shown that there are several other risks associated with the mutation. These include pregnancy-induced high blood pressure (preeclampsia), early separation of the placenta from the uterus (placental abruption) as well as slow fetal growth or intrauterine growth restriction. However, it should be highlighted that these studies have to be replicated so that these findings can be confirmed.

Conclusion

So, to wrap things up, we need to answer the question, “Why is this test important?” The guidelines for testing considerations are straightforward. Those who have venous thrombosis under the age of 50, those who have recurrent venous thrombosis as well as family history of it, female smokers who suffered myocardial infarction under the age of 50, venous thrombosis in pregnant women or those taking oral contraceptives, women with recurrent pregnancy loss, unexplained severe preeclampsia, placental abruption as well as intrauterine fetal growth restriction are all individuals who can benefit from the test.

However, some research has implied that genetic testing for the mutation has been overused with little to no benefits. The claim is that finding out about having this mutation actually does not cause any change in people’s lifestyles. Furthermore, knowing that they have the mutation may only result in unnecessary worrying because so few people who actually carry the mutation develop the disease. This all holds true for those who are not at risk for thrombophilia as well as for those who are at a risk but either do not plan on becoming pregnant or are not pregnant.

However, given the problems it causes in pregnant women, the importance of the test becomes clear quickly. Surely, if a pregnant woman knew before her pregnancy that she is at a higher risk of thrombophilia because she has the mutation, she could take all the necessary precautions before getting pregnant in order to have a healthy pregnancy. There are medications that are given to those who have thicker blood so that they avoid possible pregnancy complications.

Fragile X Carrier: Carrier Testing for Fragile X Syndrome in 2018

What is Fragile X? What is a carrier? And, most importantly, what is a Fragile X carrier and why is it so important to get tested?

Let’s back up a whole lot, genetically speaking, and then bring it all back to Fragile X carrier and testing for it and the importance.

Fragile X syndrome is a genetic disorder or condition that causes intellectual difficulties and struggles with learning as well as behavior. Kids with the syndrome struggle to understand as well as process information, which means that these kids have a difficult time with learning, behavior, and development. Fragile X gene, or Fragile X Mutation, is the most common cause of inherited intellectual disability andit is also known to be the most common cause behind inherited autism.

The syndrome affects more boys (approximately 1 in every 3,600 to 4,000 boys) than girls (approximately 1 in every 4,000 to 6,000 girls), and it also affects boys with more severity, meaning that male children have much worse symptoms. Also, Fragile X syndrome is equally distributed among cultures, meaning it appears in children of all cultures and genetic backgrounds equally.

Cognitive and Behavioral Symptoms

Cognitive and Behavioral Symptoms

Fragile X syndrome is not always obvious to spot based on physical appearance and, most of all, it varies from child to child. However, there are some common characteristics that are observed among all affected kids. These include prominent ears, a long and narrow face, poor muscle tone, flat feet, and loose joints that are a lot more flexible than usual. In terms of cognitive signs, intellectual disability and delays in development are the most common Fragile X features and many affected kids also have a hard time with fine and gross motor skills as well as delayed speech development.

In terms of behavior, observable differences or delayed development can be apparent in affected kids. Some of the typical signs include attention deficit hyperactivity disorder (ADHD), characteristics of autism spectrum disorder, shyness and/or anxiety that are particularly apparent in new situations, sensitivity to touch or loud noises, repetitive speech, difficulty with making eye contact and aggression. Some medical concerns with Fragile X syndrome children include ear infections, heart murmurs, reflux, seizures, and vision issues.

Genetics of Fragile X Syndrome

Fragile X syndrome is a genetic disorder, which means that it is caused by a genetic mutation. It is the result of a genetic mutation that is referred to as fragile X mental retardation 1 (FMR1) on the X chromosome. Most commonly, this mutation is an increase in the number of CGG trinucleotide repeats. More specifically, the disease appears to have four different forms depending on the number of the repeats of CGG in a gene. Those who have fewer than 45 CGG repeats are said to have a normal FMR1 gene, those with 45–55 CGG repeats have an “intermediate” allele, a mutation of 55–200 repeats is considered a permutation (the term permutation is used because the disease begins with a permutation that then expands to a full mutation in the coming generations) or a carrier, and if someone has more than 200 repeats of CGG, also referred to as the ‘full mutation,’ that person will suffer from intellectual disability and the aforementioned cognitive as well as behavioral symptoms. Only the full mutation will cause the FMR1 gene to shut down and stop producing the FMRP protein and the lack of this protein leads to symptoms of Fragile X syndrome.

What does it mean to be a Fragile X mutation carrier?

So, let’s get back to the carrier aspect of things. It is said that “one child is born every week with the syndrome and 20 are born with the carrier gene every week,” which means that there are a lot more carriers than there are those with actual obvious symptoms. So, who is actually considered to be a carrier? As mentioned above, any individual who has anywhere between 55 and 200 repeats of CGG in their FMR1 gene on the X chromosome is considered to be a ‘carrier.’ This means that they have a permutation or an unstable mutation that has the potential to expand in future generations and therefore cause Fragile X syndrome in their kids or grandkids. One specific feature of diseases such as Fragile X syndrome is that the genes can change size during the process of passing it on. Over the generations, the gene can change sizes and as such become more unstable and can, therefore, occur more frequently and/or severely in the following generations.

Fragile X Carrier Testing

Why get tested if you are a carrier and do not exhibit any symptoms? Well, would it not be of help to know what kind of genetic disorders you may pass on to your kids and/or grandkids? There are three circumstances around which individuals should get tested with carrier screening. These include having clinical symptoms that suggest Fragile X syndrome, (2) having a family history of the disorder, intellectual or learning disabilities or autism of unknown cause or infertility, and (3) either family or personal history of Fragile X.

DNA analysis of an individual’s sample can be as accurate as 99%, which means there’s a way to know for sure whether you are a carrier or not. Given that Fragile X is an X chromosome disorder, male carriers can only pass it on to their daughters while female carriers can pass it on to both sons as well as daughters. The inheritance is dominant, meaning that only one copy of the mutation is enough to have symptoms. Since males have only one X chromosome, if inherited, they will be affected for sure and more severely.

Ultimately, carrier screening is a fairly quick procedure and knowing early on may significantly increase a kid’s chances of overcoming the symptoms of Fragile X. With awareness having increased over the years, there are methods of teaching kids to help them advance and live normal lives.

Hemophilia Inheritance: Inheritance Patterns in Hemophilia

Hearing the term hemophilia for the first time, some of us may ask who that is rather than what it is. So,starting off with inheritance patterns may not be the best approach. Before getting into the actual patterns of how hemophilia is passed through the generations, it might be wise to first discuss what it actually is.

What is hemophilia?

The dictionary definition of hemophilia is ‘love of blood’ which was suggested for it by a medical treatise in 1828. This is rather ironic because any hemophiliac will assure you that their feelings toward the disease are far from love. Hemophilia has been referred to as a ‘royal disease’ because it was prominent among European royalty in the 19th and 20th centuries. So, what is it? Before getting into the definition of the disease, it is important to understand a few things about blood first before understanding this bleeding disorder.

Blood has two parts: one solid and one liquid part that is referred to as plasma. Red blood cells that transport oxygen and white blood cells that help fight infection as well as platelets that help coagulation make up the solid state. The liquid part is composed of proteins, salts, sugars,and water. Clotting is a process that is guided by 14 different proteins that are called clotting factors, their anomalies being a sea of several blood disorders. One of them is hemophilia, which is also known as a blood clotting disorder. More specifically, it impairs the body’s process of making blood clots, which is important to stop bleeding. Stopping bleeding is kind of an important procedure and anything that impairs that process may lead to too much bleeding and death. Individuals that have severe hemophilia have symptoms such as bleeding longer after injury, easy bruising as well as an increased risk of bleeding inside joints or the brain. Again, kind of a big bad deal.

Genetics and Inheritance

one X and one Y chromosome

Let’s talk about inheritance first before tying it to hemophilia. Females have two X chromosomes while males have one X and one Y chromosome. Upon fertilization of an egg, the female passes on one of her X chromosomes and the male passes on either his X or his Y. In the case of the former, the child will be a girl, while in the case of the latter, the child will be a boy.

Hemophilia is a genetic bleeding disorder. It is hereditary, and it affects mostly men. It is also linked to a defect in the X chromosome. So ironically confusing. In 1803, John Conrad Otto, a Philadelphian physician described it as follows, “About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants. It is one, she observed, to which her family is, unfortunately, subject and had been the source not only of great solicitude but frequently the cause of death. If the least scratch is made on the skin of some of them, as mortal a hemorrhage will eventually ensue as if the largest wound is inflicted. (…) So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation.”

In other words, he recognized that it was a genetic disease as he realized that it was passed down from parent to offspring. He also realized that it was passed down by healthy females as well as that it affected mostly males.

He was right.

So what about these inheritance patterns? Given that hemophilia is X-linked, a female who is a carrier is healthy as she has one X-linked mutation and another healthy X chromosome that compensates for the lack and does not result in blood clotting issues. In males, that is a different situation. When a carrier woman passes down her X-linked mutation to a male, he does not have another healthy X-chromosome to compensate for the lack. The Y-chromosome cannot do that, which is why hemophilia affects males a lot more frequently than females. Female hemophiliacs do exist, but only when both the mother is a carrier and the father actually has hemophilia and the two make a female baby. This is because the disease is recessive, meaning that symptoms are only apparent when females have two copies of the mutation. On the other hand, for males to have the disease, it is enough for the mother to be a carrier. One copy of the mutation on the X chromosome is enough to cause disease in males.

Add to this the fact that about 30% of the disease is a de novo mutation, meaning that it affected an individual spontaneously without prior hemophilia inheritance history.

Symptoms

Given that the disease is marked by a problem with blood clotting, it should come as no surprise that the symptoms are related to a lot of frequent bleeding situations such as frequent internal bleeding and hemorrhage, which can occur spontaneously or as a result of a bump or an injury. As the amount and frequency of these bleeding episodes vary from person to person, hemophilia has been put into three different categories that each differ based on the severity, namely severe, normal and mild hemophilia. Some hemophiliacs bleed only once a month, while others with more severe hemophilia are affected much more frequently such as several times a week.

Treatment

The number of hemophiliacs who are leading normal lives has increased drastically over the last 50 years or so thanks to clotting factor concentrate. The treatment comes in little bottles that can be stored at home and it is used in the case of a bleeding. As with many diseases, hemophilia has both physical as well as psychological effects on those who have it, which is why a combination treatment along with awareness is of utmost importance for long-term success.

Can Dogs Have Down Syndrome? What a Pet Owner Needs to Know

The bond between the human and the canine species dates back centuries. Given a dog’s ability to be loyal and to love unconditionally, it comes as no surprise that the two species have been linked for longer than we can imagine. To paraphrase Josh Billings (a.k.a. the humorist and lecturer Henry Wheeler Shaw), “A dog is the only thing on earth that loves you more than he loves himself.” So, if man’s best furry friend can feel similar things to humans, this begs the question of whether pups can suffer from the same medical conditions as humans. This comes as no surprise, as dogs can suffer from behavioral disorders such as depression or anxiety. They can even suffer from certain types of cancer, diabetes, epilepsy, and congestive heart failure—and this is naming just a few examples.

But can the canine species suffer from genetic disorders or chromosomal abnormalities that have so far only been linked to the human species? In particular, can dogs have Down Syndrome? The answer is not so clear. And why is that? Let’s first look at human Down Syndrome.

What is Down Syndrome in humans?

According to the National Down Syndrome Society, Down Syndrome is referred to as a condition when someone has either a complete additional or a partial copy of chromosome 21. So, what is a chromosome, you may wonder? And why does an extra copy or extra chromosome cause problems? Well, it turns out that a lot of things in the human body have to function just the way they are, otherwise problems arise. All of our genetic material is stored in a cell compartment called the nucleus. Every cell has it. Genetic material is stored in genes which carry information that determines all the inherited traits. Genes are organized on rod-like structures or chromosomes. Each nucleus has 23 pairs of chromosomes, one from the mother and one pair from the father. In case of the extra material of chromosome 21, also called a trisomy, Down Syndrome is the consequence.

Down Syndrome Symptoms

Down Syndrome Symptoms

There are several effects that are associated with extra genetic material. The most obvious is a degree of intellectual impairment and this varies between individuals. The US Centers for Disease Control and Prevention (CDC) states that there are some common physical features of Down Syndrome such as a flattened face around the bridge of the nose and small ears, hands and feet. Several medical problems are also common among people with Down Syndrome. These include hearing loss, frequent ear infections, eye diseases, obstructive sleep apnea as well as heart defects that are present at birth.

Can Dogs Have Down Syndrome?

Can they? It all depends on how one looks at the question. Let’s preface this section with the fact that genetic research in dogs is not nearly as advanced as in humans. Along those lines, few individual canine chromosomes or genes have actually been analyzed or sequenced.

According to the CDC, approximately 1 in every 700 babies and children in the United States has Down Syndrome. This cannot be said about dogs with the same certainty. What is known, however, is that if the disorder occurs in dogs, it is much rarer than in humans. While there are several genetic similarities between dogs and humans, it is not known whether what happens in the human chromosome 21 will have the same effect if it were to happen on the canine chromosome 21. The first obvious difference in disfavor of similarities is that humans have 23 sets of chromosomes and dogs have 39, which means that whatever information the human chromosome 21 carries may not be the same as the canine chromosome 21. This would mean that trisomy 21 in dogs would not end up in Down Syndrome in dogs. In fact, information on human chromosome 21 is so unique that it does not appear elsewhere on the chromosomes of other species, including dogs.

Given all this, few vets claim that Down Syndrome does exist in dogs but that the symptoms are vastly different than in humans. The typical scenario is that puppies who seem to have the condition die before they are even born. And, even if born, they do not live for very long. Add to that the trauma of being born that is too much for the puppy to handle and actually ends up in its death. Furthermore, even though human Down Syndrome symptoms appear only after one to two years, canine symptoms such as physical abnormalities and mental retardation are obvious early on. As a result, puppies may not be able to feed themselves which may in and of itself culminate in death. Lastly, the mother also tries to remove any sick puppies from the littler in order to protect her healthy young and this, too, may cause affected puppies to die early on. The overall survival rate of these puppies is about five years compared to ten to 15 years for healthy ones.

What Pet Owners Need to Know

In addition to the aforementioned symptoms, there are several other common Down Syndrome symptoms to look for in your puppy and it is advised that owners look for those symptoms in order to be able to differentiate whether the symptoms are due to Down Syndrome or due to something else like a cognitive dysfunction. Owners are also advised to be cautious to not mix up the above-mentioned symptoms with similar ones that may point to other diseases that are related to growth hormone deficiencies, too much fluid in the brain or liver problems (portosystemic shunt).

So, overall, canine Down Syndrome is a possibility, but not a certainty. While similarities between dogs, cats, and people exist when it comes to this genetic disorder (i.e. a brachycephalic head shape), dog owners should be cautious to get the correct diagnosis from their local vet especially when Down Syndrome-like symptoms may highlight some other serious cognitive dysfunction. Overall, whichever symptoms you notice, consult with your veterinarian as soon as possible as it all may be serious. Better still, it may just be a lot less serious than anticipated.

Is Cystic Fibrosis Genetic Testing Accurate And Other FAQs

What is Cystic Fibrosis?

Cystic Fibrosis (CF) is a rare genetic disease that is life-threatening. It affects approximately 75,000 people in North America, Europe, and Australia.A total of 200,000 people are affected in the US with an approximate 1000 new cases per year. Americans of Caucasian origin are most likely to be diagnosed with cystic fibrosis. Currently, nearly three-quarters of all cystic fibrosis cases are diagnosed by the age of two. Despite the many biotechnological advancements that have been made, the life expectancy of the disease is still around 40. It is a breathing disorder that affects the lungs. People who have it have a difficult time breathing properly. The best way to describe it is to imagine you are deep below the surface of the ocean. All that water above you is weighing down on you, making it impossible to breathe. You are struggling for air and the only way to breathe in some air is through a narrow straw that connects you to the area above the surface of the water. So, you carefully breathe in air in such a way that the straw doesn’t collapse. Imagine this type of breathing all your life—that is CF. This sounds frightening.

What is Cystic Fibrosis Genetics?

Mutations in the CFTR gene cause relevant proteins to break down and malfunction. This affects the cells that produce mucus, sweat, and digestive juices.

In healthy people, these juices are thin and slippery. In individuals with CF, these liquids are the opposite: sticky and think. And, rather than acting as a lubricant which helps the lungs breathe smoothly, the secretions clog tubes, ducts, and passageways. This is a particularly sticky situation in the lungs and pancreas.

This then causes a buildup of thick mucus around the lungs which causes lung dehydration and essentially makes breathing very difficult and almost impossible. In other words, the lungs cannot clear themselves. Cystic fibrosis is considered to be an autosomal recessive disorder. A mouthful, I know. That essentially means that someone who has the disease has two copies of the mutation in the CFTR gene from a carrier, say one from dad and one from mom has the disease. Though connected to family historythis is only the case if someone has two copies of the gene. This is different from so-called carriers of the mutation who only have one copy and no symptoms. An estimated 10 million Americans are a CF carrier of the mutation. This is scary if you think about it. The chances of any male and female CF carrier among the 10 million meeting and having a child are quite high. There are nearly 2,000 mutations related to cystic fibrosis, some of which can be detected via genetic screening.

Is Cystic Fibrosis Genetic Testing Accurate?

Is Cystic Fibrosis Genetic Testing Accurate

Yes, and no. Out of the 2,000 cystic fibrosis mutations that have been found, during a genetic test less than 300 are genetically testable, so to say. This has been helpful. Thanks to genetic test advancements, the life expectancy of those with cystic fibrosis has increased by ten years—from 27 to 37. These advancements have also helped doctors figure out not only which patients have cystic fibrosis, but also which ones are at risk and which drugs or medications are best suited for them. This is especially helpful for parents who wish to have a baby; genetic testing may help them figure out what the chances are their baby will have the disease. These have all greatly advanced the area of genetic testing for cystic fibrosis. However, screening of only 300 genes is not enough. This leaves the other 1,700 or so in the dark in terms of screening, but they could be important in predicting disease status. So, yes, the tests that are designed to test the less than 300 genes for cystic fibrosis are accurate, but are they enough to predict all the cases of cystic fibrosis given that there are 2,000 mutations for it? Probably not. That is why genetic screening is not considered a gold standard when it comes to diagnosing cystic fibrosis.

How Is Cystic Fibrosis Diagnosed?

Cystic fibrosis is currently diagnosed through a chloride sweat test. The science world refers to it as pilocarpine iontophoresis, but let’s just call it the sweat test for our purposes. During the sweat test, the patient takes a chemical activator (pilocarpine), which causes them to secrete chloride on their skin. The sweat test, as its name implies, measures the concentration of chloride, or essentially salt, in the patient’s sweat. This technique has been around for decades. Even though it is old, its accuracy rate is around 98%. And while it is accurate, it doesn’t provide any information other than a positive or negative result. In other words, patients and doctors can only get a yes or no answer. It offers no information about the severity of symptoms or which therapies might be most effective or suitable. This is a big deal since the severity of the disease varies greatly among patients.

What Is the Future of Cystic Fibrosis?

Despite the fact that cystic fibrosis diagnostics are not optimal, we have to look at things from the bright side and not sweat the small stuff. Great advancements have been made, indeed. This includes advances in both technology as well as treatment. Thanks to that, children with the disease are living into adulthood. In fact, over 50% of the patients with the disease are older than 18. Their median predicted survival age (meaning the most frequent survival age among the cystic fibrosis group) is constantly on the rise and is now close to 40. So, overall, perhaps rather than asking whether genetic testing for cystic fibrosis is accurate, we should be asking if it is better than before, which it definitely is. Given that the numbers have improved rapidly over the past few years, it is not unrealistic to expect more and more rapid advancements in the coming years.

Is Dog Genetic Testing a Thing?

Definitely. Genetic testing.We’ve all heard of it at some point or another. We probably all know a person or two who has had it done. (23andMe was the first company to offer DNA testing directly to consumers that look for ancestry information. Now it has expanded to diseases, as well.) Perhaps you have done it yourself and now a thing or two more about your genetic blueprint. Maybe you now know your exact ancestry makeup or even what type of diseases you are at risk for?

So, people have been doing it, at least since 2007 when 23andMe became widely available. But what about dogs? What about our furry canines?Are they purebred dogs or mixed-breed dogs? Can we check for genetic diseases through a DNA test? If we love them as we love ourselves, wouldn’t we want the same for them as for ourselves, too? So, if we are curious about our genetic blueprint, why wouldn’t we feel the same about theirs?

To the dog owners among us, have you ever wondered about the genetic makeup of your furry best friend? Have you ever wondered about your dog’s chances of having a disease? Can you be 100% sure that you know your canine buddy inside and out? If the answer is yes to all of the above, you truly know your wet-nosedbud and you’re a champ! However, if you have stopped to think about any of the questions and are not sure, now you can be! You can, in fact, find out about your dog’s genetic makeup thanks to several companies that actually do that.

A company called Wisdom Panel offers two kits—a ‘Canine Breed Detection’ that offers identification for 250+ breeds, types and varieties and a ‘Canine Breed + Disease Detection’ that, in addition to the breeds, also offers screening for 150+ genetic health conditions. Their tagline, “Get to know your soul mutt even better”—all that is required is a pup’s cheek swab, an online kit activation,and prepaid shipping, and you’re on your way to unleashing yet another layer of your dog’s persona. Among the several things they offer, Wisdom Panel will provide you with a customized online report that has a genetic analysis of your dog’s ancestry, weight, physical traits and up to 150+ health conditions.

Embark is another such company

Embark is another such company that offers genetic testing services for dogs. However, they have a slightly different approach. According to their website, they are “the world leader in dog genetics” whose scientists have traveled the world to bring their clients a revolution in dog care. Embark is a research partner of Cornell University College of Veterinary medicine, and as such have a somewhat more academic or research approach—they use the information they obtain from clients for research purposes, too, to “expand the understanding and practical application of genetic knowledge in veterinary care and dog wellness generally.” They offer just one kit, the Embark Dog DNA Test, via which dog owners can find out their dog’s breed ID, genetic ancestry, over 160 diseases as well as traits such as coat color and altitude adaptation.

There are several other canine DNA companies out there that will screen your dog’s DNA and essentially offer insight into your dog’s past, present, and future.

In addition to dog owners finding out valuable information in regards to their dog’s genetic blueprint, this area has several other applications. In other words, it is not just for dog owners. Some companies offer forensic services for a growing discipline termed veterinary forensics. It is used in situations such as animal abuse, fraud, and criminal investigations and offers insight into law enforcement, Human Societies,and insurance companies, to name a few. And yet other companies offer services for dog breeders who wish to remain informed about the health risks of their specific breeds. Veterinarians also benefit from these services as they can offer their clients personalized pet medicine if they choose. This would enable them to have a medical angle to the DNA other than just being curious about their pet’s ancestry or disease background.

In addition, testing for dog DNA can also help future down owners—those who wish to either purchase a dog or adopt one. It would be helpful to not only know the breed breakdown but also what the potential disease risks are as well as how big the dogs will grow up to be and what their personality will be like; this can greatly facilitate adaptation of the owner to the dog and vice versa. Also, knowing the risks of disease upfront can save dog owners thousands of dollars down the line. Knowing that heart disease or cancer are potential risks before they happen is certainly an advantage. In other words, pet owners are prepared for the worst. DNA testing enables them to be ready, in addition to just being informed about the fact that their dog is a mutt/purebred/etc.

So, to get back to the question “Is dog genetic testing a thing?”the answer is a resounding yes. Once considered a new technology fueled by curiosity and only aimed to address the ‘just because,’ it has expanded to address several practical issues when it comes to pet genetics. But given all that, genetic information should still be taken with a grain of salt. It is not the end all be all—just because you have found out that your little furry friend has some cancer genes, it does not mean that he will have it for sure. That just means that there is a potential for it and now you know.

So, dog DNA testing is a thing, but that is not where the story ends. But you were probably able to predict that. Cat owners can benefit from these services as well. So, can horse owners!

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