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Down Syndrome Article Review

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BIOL 2040 Reading Assignment

Humair Mallik
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August 14, 2015

Blood test for pregnant women reveals if unborn baby has Down's syndrome
By DAILY MAIL REPORTER
UPDATED: 12:13 GMT, 7 March 2011

Doctors have developed a blood test to check unborn babies for Down’s syndrome.
The approach could save pregnant women from having the invasive examinations currently available, which raise the risk of miscarriage.
Current blood tests can only tell if a baby is at risk of Down's Syndrome.
Scientists from Cyprus, Greece and Britain said the new technique correctly identified 14 Down syndrome cases and 26 normal foetuses in a blind test. They believe it will also be possible to diagnose the condition earlier on.
Study author Philippos Patsalis, of the Cyprus Institute of Neurology and Genetics, said: 'The method is simple and fast and easy to perform in every genetic diagnostic lab worldwide because it does not require expensive equipment, software or special infrastructure.
'The test is the first worldwide to demonstrate 100 per cent sensitivity and 100 per cent specificity in all normal and Down's syndrome pregnancies examined.'
Down's syndrome is a genetic disorder that causes physical and learning disabilities and raises the risk of heart disease.
Infants with the condition have three copies of the Chromosome 21 instead of the normal two.
It affects about one in every 700 live births but women of 40 are 16 times more likely to have a Down's child than a 25-year-old.
At present all pregnant women are offered screening to see if their baby is at risk of Down's syndrome. For a firm diagnosis, doctors must take a sample of amniotic fluid or the placenta, which involves a 1 in 100 risk of miscarriage.
Several research teams have published studies suggesting that analysing the mother's blood can detect Down syndrome in a foetus.
There is no commercial test available yet, but at least one company hopes to introduce one in the U.S. within about a year.
The team behind the latest findings, published online in the journal Nature Medicine, said a bigger study is needed to confirm the usefulness of their approach.

Checking for Down syndrome prenatally has been an informative feat; knowing whether the child would have the disease before the birth actually takes place certainly has its advantages. These days, it is done so for virtually every baby. Up until recently however, the invasive methods of doing so has drawbacks, namely a high rate of miscarriage (a 1% chance). This article suggests that in the year 2011, doctors had developed a method for that is not invasive, eliminating the drawbacks that are usually associated with the prenatal testing. Also, this new technique claims to diagnose the disease earlier on and with a definitely accurate (100 percent) diagnosis unlike the method that pre-existed it, which was only able to tell if the baby would be at risk of the disease. The new method “correctly identified 14 Down syndrome cases and 26 normal foetuses in a blind test”, done by scientists from Cyprus, Greece, and Britain. The Cyprian, Philippos Patsalis, authored the study and said that the test could be done easily and affordably by any genetic lab as it was inexpensive and easily accessible. However, it was not available for commercial usage when this article was published. Orthodoxly, testing for Down syndrome is done through sampling and analyzing blood. Blood markers are utilized to determine the risk for the fetus during the first or second trimester. Testing of alpha fetoprotein, unconjugated estriol, total hCG, and free beta hCG is usually done. Combined with ultrasounds, a clearer picture can be formed. Invasive techniques (amniocentesis, CVS) used to test the mother’s blood can confirm test results. This new technique that the article talks about also uses blood testing for diagnosis. It is however a less invasive and supposedly safer venue. It makes use and studies the difference in methylation of the DNA of the mother and of the fetus. In doing so, fetal-specific DNA could be identified. By using massive parallel sequencing, the scientists (Patsalis et al) had correctly diagnosed 98.6% of pregnancies, with a 0.2% rate of false positives. Today, this non-invasive technique is preeminent commercially. This method still however requires positive tests to be confirmed by invasive methods, and it also fails to recognize half the defections that could be detected through invasive measures. For the time being, this method of testing for Down syndrome is not primarily recommended but may be used in special cases where invasive methods would be detrimental.
Down syndrome, another name being trisomy 21, is a genetic mishap that causes a person to have an extra chromosome copy of chromosome 21, making it 3 copies in total. The karyotype for this phenomenon shows that every chromosome has 2 copies, while number 21 has 3 copies, the third being present fully or partially. Thus, it can also be written as 47, XX (or XY), +21[47 chromosomes in total, XX for female or XY for male, and +21 for the extra chromosome 21 present].
A person affected with this disease would have many abnormalities. Physical traits include a small chin, flat wide face, short neck, almond shaped eyes, weak muscle tone, excessive joint flexibility, extra space between the 1st and 2nd toe, short fingers, a flat nasal bridge, a single crease on the palms, and a relatively small mouth and large tongue. The IQ of a young adult diagnosed with Down syndrome is around 50, about the IQ of an 8 or 9 year old child. The older the person gets, a higher degree of speech impediment persists. The senses are also affected. Vision problems include strabismus, cataracts, keratoconus, glaucoma, and brushfield spots also exist. Hearing issues include otitis media with effusion, and chronic ear infections. The heart also takes a toll through this disease. Atrioventricular/ventricular septal defect, mitral valve problems, tetralogy of Fallot, patent ductus arteriosus are all issues that can be apparent readily. Other areas of negative influence include thyroid functionality, gastrointestinal issues, and reduced fertility.
Even though an affected child could have all these issues, the parents of the child are usually normal. The disease is mostly not inherited. Other factors in fact usually arise to cause the disorder. For trisomy 21, abnormality in the form of nondisjunction occurs randomly during formation of reproductive cells in parents. This error in division, which mostly occurs in the egg but can also occur in sperm cells, causes a cell to retain an extra copy of chromosome 21. When this sec cell is combined with its complementary sex cell and creates a zygote, the fetus will develop this disease. Approximately 88% of cases of trisomy 21 shows that the nonseperation had occurred in the mother, 8% it occurred in the father, and 3% it occurred after the zygote had formed. Another way an extra set of chromosome 21 appears is due to Robertsonian translocation, though it is relatively rare. A male with this affliction has a karyotype of 46, t(14q21q), which is mainly due to interactions with chromosome 21 and 14 resulting in a new mutation or is inherited from a parent. This parent would appear normal but his/her sex cells have an increased chance of having extra chromosome 21 genetic material. With trisomy 21, the older the mother is, the higher the chance for this disease to develop in the fetus. With translocation however, the mother’s age is a nonfactor. This extra genetic material of chromosome 21 causes an overexpression (of about 50%) some genes on that chromosome. Some, and not all, research has shown that the critical zone that is overexpressed is at bands 21q22.1 to q22.3. This region contains genes for amyloid (whose overexpression causes the mental disorder associated with people with Down syndrome), superoxide dismutase, and ETS-2 proto oncogene. Senile plaques, neurofibrillary tangles, and lack of lymphocytes leading to infections can develop due to the overexpression as well.
Epigenetics can also be at play in Down syndrome and help to better understand the disorder. Diseases that are incurred due to having Down syndrome usually transpire in normal adults at old age. This suggests that Down syndrome causes one’s cells to age faster than normal, but researches do not point to this situation. Using the epigenetic clock, a tissue biomarker, it was shown that someone with Down syndrome (trisomy 21 namely) would have an increased lifespan of the blood and brain tissues by about 6.6 years more than normal.

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