Showing posts with label genes. Show all posts
Showing posts with label genes. Show all posts

Monday, September 21, 2015

Everything You May Not Have Realized You Wanted to Need and Know About Genomic Sequencing

By: Lewis First, MD, MS; Editor-in-Chief         
     More and more we are recognizing the benefits and the risks, especially ethical risks of genomic sequencing studies on pediatric patients.  If you have not yet had a patient need genomic sequencing, it is only a matter of time until this technique becomes cost-effective and available to be ordered at the primary care level—maybe not just yet, but it’s coming soon.  To help all pediatricians better understand how to communicate and in turn interpret these tests, given the uncertainty of the data we can now get through sequencing, some assistance is needed.  Fortunately this week we are releasing two articles that we feel are good ones to read and file in your folder of articles to turn to when faced with a family asking or whom you feel needs genomic sequencing.   
     McCullough et al. (doi: 10.1542/peds.2015-0624) offers an ethical backbone to help us disclose results to families who have sequencing performed on their child.  This special article guides us through the process of how to recommend sequencing and then discuss the results and implications using core concepts of medical ethics.  Adding to this article is an accompanying commentary by geneticist Dr. Leah Burke (REF) that provides insight into how sequencing will become more and more integrated into the care we deliver.           
      Read the article and commentary in sequence and you’ll probably find yourself referring back to both as genomic sequencing becomes more and more a part of primary and specialty care practice.

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Tuesday, April 1, 2014

Case Report: Buccal Cell Chimerism in a Monochorionic Dizygotic Twin

Our Case Report Editor, Dr. Jeffery Malatack shares a case report we early released this month from our upcoming April issue:

Public Domain Photo
A case report has the capacity to bring to attention an observation that challenges the existing understanding of nature even when the implications of this paradigm alteration aren’t known.

Such is the case with the report by Fumoto and colleagues at the Kyorin University School of
Medicine’s HLA laboratory in Kyoto, Japan (doi: 10.1542/peds.2013-1938). Not until recently has the existence of monochorionic dizygotic twins (MCDZT) been known.

Prior to work by Souter et al. in 2003, monochorionic twins were believed to all be monozygous. Subsequent to Souter’s publication, MCDZT were recognized to be not extremely rare particularly in pregnancies by in vitro fertilization. Once such twins were recognized blood chimerism between such twins was noted to occur fairly often. Blood derived from one zygote was found in the blood stream of the twin derived from the other zygote and vice versa.

This finding, it is assumed, occurs when placental vessels cross during in-utero development mixing one twins blood elements with the others. Until Fumoto’s report, only blood elements were known to be chimeric in MCDZT and only on occasion. Fumoto upsets that notion by finding chimeric buccal cells in each of a twin set. The authors speculate on the mechanism of this finding and possible implications of its occurrence in the report.

It appears that the more deeply we look into biology, the more we find exceptions that no doubt are new harbingers of deeper understanding of nature’s overall plan.

Friday, November 22, 2013

Genes and Obesity

Associate Editor Dr. William V. Raszka offers insight into topics in the news. This week, he reflects on recent research into genes and obesity: 

A friend of mine has wrestled with being overweight for years. She is very careful about her diet, exercises maniacally, and limits her alcohol consumption.  Despite these efforts, her BMI has always been > 30.  Her weight does not seem to be related to lack of self-control and is not easily understood. My friend’s weight problems may be due to her genes. 

As reported in The New York Times (July 19, 2013), researchers have known for a long time that some aspects of weight gain are hereditary. Twins raised apart tend to have the same weight, while adopted children tend to have the body mass of the biologic parents, not their adopted parents. Evidence has accumulated over time to suggest that dozens of genes may be involved in increasing appetite, and new research suggests that at least one gene is associated not only with appetite but with a change in mammalian metabolic rate. 

The investigators developed knockout mice deficient in brain and body expressed “melanocortin receptor accessory protein 2” (MRAP2). When allowed to eat as much food as desired, the MRAP2 deficient mice were voracious and quickly became extremely obese.  When MRAP2 deficient mice were fed the same number of calories as normal mice however, only the MRAP2 deficient mice became obese. The MRAP2 mice had to be fed 10 to 15 percent fewer calories in order to demonstrate the same weight gain as their normal siblings.  How MRAP2 controls weight gain is not entirely understood, but researchers suspect that MRAP2 regulates “melanocortin 4 receptor” (Mc4r), a protein previously implicated in mammalian obesity. Without MRAP2 production, appropriate appetite and energy metabolism regulated by Mc4r is impaired. Interestingly, four children in a registry of 500 severely obese children were found to have alterations in the MRAP2 gene while none of the healthy controls in the same study did.

While still very preliminary, researchers are now looking for alterations in the MRAP2 gene that could lead to partial expression and hence, explain some of the variance in weight gain among people consuming the same number of calories. While it will not help my friend lose weight, I think she will appreciate learning that obesity is not always about loss of self-control.

*This filler excerpt can be found in the November 2013 Pediatrics print journal p. 871, or online here.