A Risk-Free Test for Down’s

April 18, 2014

By Medical Discovery News

Keep Calm, It's Only An Extra Chromosome

When it comes to chromosomes, extra copies are not a good thing. Every cell in the human body carries the same genetic information in two copies of 23 chromosomes. Having an extra copy of a chromosome is called trisomy, and an extra copy of chromosome number 21 is what causes Down syndrome.

Physical signs of Down syndrome include upward slanting of the eyes, flattened facial features, small and unusually shaped ears, small heads, and broad hands with short fingers. Down syndrome can also cause more serious conditions such as varying degrees of mental retardation, poor muscle tone, an increased risk of early onset dementia, and heart, stomach, and eye problems. No two cases of Down syndrome are the same, and with therapy and support people with Down syndrome can live long, productive lives.

The risk of Down syndrome increases with the mother’s age during pregnancy. The risk of having a baby with Down syndrome increases from one in 1,300 to one in 25 at ages 25 to 49.

Women who are pregnant with a child who might have Down syndrome typically undergo an ultrasound test and blood tests for markers such as pregnancy-associated plasma protein-A and a hormone known as human chorionic gonadotropin. Abnormal levels of these markers may indicate a problem with the baby. These tests are generally done during weeks 11-13 of pregnancy. The American College of Obstetrics and Gynecology now recommends that all women undergo prenatal testing for chromosomal abnormalities.

Until recently, Down syndrome could only be confirmed by invasive tests that collect cells from the amniotic fluid surrounding the fetus, the placenta, or the fetus itself. These tests can be risky, with a one percent chance of miscarriage. However, a new, noninvasive screening test called circulating cell-free fetal DNA analysis may reduce the need for invasive prenatal tests. Circulating cell-free DNA from the fetus makes up three to 13 percent of the DNA fragments circulating in the mother’s bloodstream during pregnancy.

First, DNA is isolated from the mother’s plasma, the liquid component of blood. Then, there are two ways to determine if there are any chromosomal abnormalities. Massive parallel DNA genomic sequencing can be used to quantify millions of DNA fragments in just a few days and can accurately detect trisomies. Another approach is called Digital Analysis of Selected Regions, which analyzes only the chromosomes in question to evaluate them for any abnormalities.    

These tests are 99 percent accurate, can be done as early as the 10th week of pregnancy, and are more reliable. They can also diagnose other trisomies, like the ones that affect chromosome 18 (Edwards syndrome) and chromosome 13 (Patau syndrome). At this stage, invasive testing is still required to confirm the diagnosis of a trisomy. But in the near future this new technology will reduce or eliminate the need for additional invasive tests that put the fetus at risk. This is only the beginning of the development of safer and more accurate genetic tests.

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The Human Genome Revisited

March 1, 2013

By Medical Discovery News

When scientists sequenced the human genome in 2000, it revolutionized biomedical research, much like the invention of the Internet forever changed communications. The project aimed to identify all the genes in the human genome.

At first, they estimated that humans had less than 100,000 genes, then improved methods lowered that to 35,000, and a new analysis suggests that humans have no more than 21,000 genes. When considering the complexity of a human being, that number does not seem very high.

However, even the highest of those estimates accounted for less than 20 percent of the DNA sequence in the human genome. The rest of sequence did not appear to encode genes that led to proteins and was therefore considered non-functional or “junk” DNA.

Now a recent study by more than 400 researchers at 32 institutions costing almost $300 million challenges that notion and suggests that more than 80 percent of the human genome is indeed utilized and therefore important in the overall biology of each person – so much for “junk” DNA. The Encyclopedia of DNA Elements (ENCODE) project concluded that 20,687 genes produce proteins and an additional 18,400 genes produce RNA involved in coordinating the activity of the genes that produce proteins. 

This extensive effort originally focused on the genomes of a small number of human cells but later expanded to include almost 150 different cells, including immune, embryonic, liver tissue, umbilical cord, and cancer cells. Specific genes produce proteins for different tissues at different stages of human growth, so using this wide array insured that the analysis included all active genomic regions and gave a broader view of the genome. 

The analysis also identified genome regions associated with specific human diseases, creating an opportunity for better understanding these diseases and treating them. In addition, the ENCODE project revealed just how different humans are from other mammals like monkeys, dogs, or dolphins. While previous estimates suggested that just 5 percent of the human genome is unique from other animals, ENCODE’s research doubled that estimate to almost 10 percent. Another revelation showed just how complex the control mechanisms of the human genome really are. They signal almost 20,000 genes at the exact time and location to allow a fetus to develop normally and instruct the specific workings of tissues, like in the kidneys, lungs, or brain.

So the action of genes is controlled by layer upon layer of interacting and intricate controls that make each person who they are. Homo sapiens are a species of biological wonder and will require many years of intense study to even begin to understand the mysteries of how genes are regulated to make a human being. 

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The Little Denisovan Girl and Us

Jan. 4, 2013

Medical Discovery News

We are now able to analyze the genomic sequences of prehistoric humaniods to learn how they differed from modern humans

The words screamed off the page:  “Genomic Sequencing Brings Ancient Girl to Life!” While such headlines bring to mind reanimated mummies, they actually referred to the successful extraction and complete genomic sequencing of a young girl who lived 80,000 years ago. This is the first time the quality of the genomic sequence of any ancient species has rivaled that of the living people today.

This study pioneered a new approach in DNA sequencing. DNA, while known to be hardy, cannot usually be extracted in the double stranded form from fossils like it can be from living organisms today. Researchers used a small piece of the knuckle of her pinky finger to extract the girl’s ancient DNA.

Researchers developed an effective strategy utilizing the single-stranded DNA fragments they extracted. This new approach generated up to 20 times more readable DNA sequences than previous methods could have. In the end, researchers put together a high-resolution genomic sequence.

The quality of the sequence amazed scientists because it matches the resolution of genome sequencing from living organisms today. For example, they determined that the girl had brown skin, hair, and eyes. 

The girl’s sequence holds important hints of human evolution. She belonged to a lesser-known sister species to Neanderthals called Denisovans, which have only been found in Southern Siberia. It was obvious that she had 23 pairs of chromosomes, the same as modern humans. Chimpanzees have 24 chromosome pairs, so Denisovans were definitely more human than ape-like.

By aligning differences in the DNA sequences, scientists estimated that the Denisovans split from humans between 170,000 and 700,000 years ago. When compared to chimpanzee sequences, there were fewer differences than those between modern humans and chimpanzees.  Due to the new sequencing technique, scientists can more accurately date when a fossilized person or animal lived and died. Such advances may alter the time frame of human and animal evolution.

Other recent studies indicate 1 to 4 percent of European and Asian DNA came from Neanderthals. Since Africans have no Neanderthal DNA, interbreeding between Neanderthals and humans occurred after humans left Africa and migrated to Eurasia. Only humans from Papua, New Guinea, shared DNA with Denisovans, but a trace amount of similarity was seen in the genomes of the Han and Dai peoples in mainland China. Scientists don’t yet know the connection between these groups.

Overall, researchers documented more than 100,000 DNA sequence changes between Denisovans and modern humans. Of high interest were eight changes in genes that play a role in the “wiring” of the human nervous system, including one linked to autism and one associated with speech defects, raising questions about the speech and mental capabilities of these early ancestors. Scientists will continue to learn more about early humans and their predecessors using this new approach to DNA sequencing as a “molecular time machine.” 

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