In Science of Down Syndrome, Another Piece of the Puzzle

20 May

A few news articles recently reported that after studying a pair of identical twins where only one had Down syndrome, scientists in Europe determined some new information about how having Trisomy 21, a third copy of the 21st chromosome, affects a person’s genetic material. You can read the articles here and here. For a scientific take that is still fairly easy for a layperson to understand, read this one in Science Daily.

Myself and some other parents who have children with Down syndrome were unsure what this research meant and were confused by some of the wording in these articles. To decipher this for my non-scientific brain, I contacted Dr. Michael Harpold, who has more than 35 years experience as a biomedical researcher and is the chief scientific officer for LuMind Foundation (formerly the Down Syndrome Research and Treatment Foundation) the largest non-governmental source of funding in the United States for Down syndrome cognition research.

After speaking with Dr. Harpold, I gathered that the basic takeaway from the study was the finding that having an extra copy of chromosome 21 affected the expression of genes on all chromosomes, and even altered the very structure of all the chromosomes.** (See Footnote).

Most people understand that the third copy of the 21st chromosome means that genes on that chromosome will be over expressed, said Dr. Harpold, and scientists have known for some time that it also affects gene expression on other chromosomes, with some genes being over expressed and others being under expressed.

But Dr. Harpold said the new findings indicate that genes on every chromosome, not just some, are affected. In addition, some of the gene expression alterations may be occurring because of structural changes in the chromosomes.  These changes, he said, were shown to occur in regular patterns – in other words, they are not random. Scientists aren’t sure which genes specifically are altering the chromosomal structures, but this study opens up a pathway for them to investigate, Dr. Harpold said.


Chromosomes, playing with extrusions © Jan Montarsi

“The consequences of this alteration in chromosome structure remains incompletely defined and will require additional research to understand specific effects,” Dr. Harpold said. “Based on this recent study, these alterations in chromosome structure correlate with differences in gene expression. Some of these differences in regulation of gene expression would be expected to contribute to some of the characteristics and medical problems as well as their variation between individuals in Trisomy 21.” For instance, this research may open doors in the future to understand why some people with Down syndrome have complex medical or behavioral issues, while others are less affected.

The study, he said, is “very important from the standpoint of opening up new thoughts about the mechanisms involved in Trisomy 21.”

The beauty of this particular study, he said, is that it eliminates the natural genetic variability among individuals, because other than the extra copy of the 21st chromosome, the twins share the same DNA. “As far as I know, this is the first time that somebody has done this exact study,” he said. As for those confused by how twins can still be called identical if only one has Down syndrome, Dr. Harpold said that while this situation is rare, it isn’t unheard of. It likely resulted from a random event during early cell division, where one twin received a third copy of the 21st chromosome and the other didn’t. Scientists can’t fully explain why that happens, he said.

The study involved an investigation of the chromosome structure and genes expressed (the RNA copies of the genes) in cells from each of the twins, said Dr. Harpold. In part, it expands on what scientists already know. “ This new study confirms the fact that some genes on other chromosomes are either over or under expressed,” he said, “it’s not a fluke.” Because of the natural gene variation occurring between unrelated individuals, Dr. Harpold said, it is not yet possible for the researchers to show whether or not the same pattern occurs in every individual with Down syndrome. It’s possible that the patterns would be similar, he said.

So, I wondered, what does this mean for the future of research?

“This new study opens the doors for further investigating which over-expressed genes on chromosome 21 or other mechanisms may be responsible for altering chromosome structure and gene expression in Trisomy 21,” Dr. Harpold said. “Such investigations could provide deeper understanding of underlying mechanisms involved in various medical problems experienced by individuals with Down syndrome and lead to development of new types of therapies. Further research based on the results in this new study may also provide new insights relevant for other trisomies.”

One thing the study does not do, Dr. Harpold said, is revise what science understands to be the root “cause” of Down syndrome, which at the most fundamental level is a third copy of the 21st chromosome, the smallest of the human chromosomes.

Another thing that myself and other parents wondered was whether this research would complicate current cognition research. (We thought it was complicated enough when just the 21st chromosome was involved.)

In terms of ongoing research into drug therapies to improve learning and memory and prevent Alzheimer’s disease, he said that the study doesn’t affect anything currently in the works. “I think that as a researcher,” Dr. Harpold said, “it’s very interesting and opens up new pathways for additional research, but relative to the ongoing cognition research, the results of this new study do not say or indicate anything that’s been done is wrong or won’t work, it’s just a different layer.”

“It doesn’t directly or immediately impact the mechanisms or targets or drugs currently being studied,” he continued. “It may lead, however, to a greater understanding for potentially refining these approaches, but it doesn’t say they’re wrong.”

Here in Charlotte, I asked Campbell Brasington for her insight into what this study was telling us. She is a certified genetic counselor at the Down Syndrome clinic at Levine Children’s Hospital. She has written her own paper about the Nature study and you can find it here. (Scroll down to the bottom of the page.)

“Obviously, this study raises many more question than it answers,” she said, “but that is not new to anyone who has been following genetics over the past few decades. Certainly the development of new genetic technologies has outpaced our understanding of how many of these new findings are used and interpreted for our patients we see in our clinic and how they can be applied to clinical care.”

“This study’s findings do open many new doors for other ways to look at Down syndrome and how we might develop effective treatments that will improve overall health, cognition and quality of life for children and adults with Down syndrome,” she continued. “This will build upon and enhance research already ongoing and may also help in understanding the effects of other trisomies, such as Trisomy 18 and Trisomy 13.”

“Personally, “ Ms. Brasington said, “I am excited by this study because it shows that researchers are continuing to think about Down syndrome in new and innovative ways and how it affects the people we know and love who have Down syndrome so that future generations will benefit.”

For my part, I obviously don’t know what effect this research will someday have on our family or our son with Down syndrome, who is 5. But the disobedient rebel in me is getting a kick out of the idea that something about our son is, once again, more complex than we first thought.

Please keep in mind that I undertook asking the questions in this post mainly out of curiosity – I am fascinated by scientific research and briefly considered neuroscience for post-graduate studies (yes, people who’ve known me forever, it’s okay to laugh here). I am not promoting this research as something we should be excited about, but on the other hand, I see no reason to fear it, for I’m not sure it’s possible at this point to feel one way or the other. A special thank you to Dr. Harpold for patiently wading through my ignorance to answer questions and to Ms. Brasington, who is on the board of our local support group, the Down Syndrome Association of Greater Charlotte.

By writing this, my intent was not necessarily to enlighten, but to let you know there is an interested party watching and questioning. I hope that we can always be partners in curiosity when it comes to our children with intellectual disabilities. Please share your thoughts in the comment section below, or on my Facebook page. If you have additional questions, please post them below and I’ll try to ask one of the scientists.

** FOOTNOTE: For those who need a refresher on genes, cells and DNA – myself included – visit this great website from the National Library of Medicine.




2 Responses to “In Science of Down Syndrome, Another Piece of the Puzzle”

  1. plus15campaign May 20, 2014 at 10:38 am #

    Reblogged this on The plus15 Blog and commented:
    LuMind’s Dr. Michael Harpold contributes to an article where a parent of a child with Down syndrome asks about the latest scientific studies.


  1. Ds Research Questions: Asked by a Parent, Answered by Experts | Plus15 - August 19, 2014

    […] counselor at the Down Syndrome clinic at Levine Children’s Hospital. Then Victoria captured the answers in her blog, so she could share what she […]

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