Monthly Archives: April 2013

Apr. 2, 2013 Children with autism have increased levels of genetic change in regions of the genome prone to DNA rearrangements, so called "hotspots," according to a research discovery to be published in the print edition of the journal Human Molecular Genetics. The research indicates that these genetic changes come in the form of an excess of duplicated DNA segments in hotspot regions and may affect the chances that a child will develop autism -- a behavioral disorder that affects about 1 of every 88 children in the United States, according to the Centers for Disease Control.

Earlier work had identified, in children with autism, a greater frequency of rare DNA deletions or duplications, known as DNA copy number changes. These rare and harmful events are found in approximately 5 to 10 percent of cases, raising the question as to what other genetic changes might contribute to the disorders known as autism spectrum disorders.

The new research shows that children with autism have -- in addition to these rare events -- an excess of duplicated DNA including more common variants not exclusively found in children with autism, but are found at elevated levels compared to typically developing children.

The research collaboration includes groups led at Penn State by Scott Selleck; at the University of California Davis/MIND Institute by Isaac Pessah, Irva Hertz-Picciotto, Flora Tassone, and Robin Hansen; and at the University of Washington by Evan Eichler.

The investigators also found that the balance of DNA duplications and deletions in children with autism was different from that found in more severe developmental disorders, such as intellectual disability or multiple congenital anomalies, where the levels of both deletions and duplications are increased compared to controls, and are even higher than in children with autism.

They also found that children who had more difficulty with daily living skills also had the greatest level of copy number change throughout their genome. "These measures of adaptive behavior provide an indication of the severity of the impairment in the children with autism. These behaviors were significantly correlated with the amount of DNA copy number change," Selleck said, emphasizing that the research revealed "clear and graded effects of the genetic change."

"These results beg the question as to the origin of this genetic change," Selleck said. "The increased levels of both rare and common variants suggests the possibility that these individuals are predisposed to genetic alteration."

A vigorous debate is ongoing in the research community about the degree of genetic versus environmental contributions to autism. Selleck said the finding of an overall increase in genetic change in children with autism heightens the need to search for the basis of this variation. "We know that environmental factors can affect the stability of the genome, but we don't know if the DNA copy number change we detect in these children is a result of environmental exposures, nutrition, medical factors, lifestyle, genetic susceptibility, or combinations of many elements together," Selleck said. "The elevated levels of common variants is telling us something. It suggests that pure selection of randomly generated variants may not be the whole story."

The Penn State team includes Department of Biochemistry and Molecular Biology Associate Professor Marylyn Ritchie and Assistant Professor Santhosh Girirajan. "The relationship between the level of copy number change and the degree of neurodevelopmental disability is something we have noted previously for large, rare variants" says Girirajan, "but this work extends those observations to common copy number variants, suggesting the level of copy number change in children with autism is larger than we had appreciated." Girirajan, the first author of the study, coordinated the effort between the Penn State and University of Washington researchers.

The research collaboration began with studies supported by the Minnesota Medical Foundation and the Martin Lenz Harrison Endowed Chair in Pediatrics when Selleck was Director of the Autism Initiative at the University of Minnesota. When Selleck arrived at Penn State in 2009, he began a new phase of the analysis with replication studies of early findings conducted with the help and expertise of Evan Eichler and colleagues at the University of Washington using the clinical data and DNA collected by Isaac Pessah, Irva Hertz-Picciotto, Flora Tassone, and Robin Hansen at the University of California Davis/MIND Institute group, which directs a large population-based case-control study of autism called CHARGE (Childhood Autism Risks from Genetics and Environment). In this multiyear study, clinical history, environmental, nutritional, family, and medical data are collected from the families of children with autism and other developmental disorders, as well as from randomly selected control children from the general population. The research took advantage of the CHARGE study, supported by the National Institute of Environmental Health Sciences and the Environmental Protection Agency.

Read more:
Autism linked to increased genetic change in regions of genome instability

(Charles Dharapak/AP)

Every dollar we spent to map the human genome has returned $140 to our economy -- $1 of investment, $140 in return.

--President Obama, Remarks by the President on the BRAIN Initiative and American Innovation, April 2, 2013

Every dollar we invested to map the human genome returned $140 to our economy.

--Obama, 2013 State of the Union address, Feb. 12, 2013

In announcing a new government initiative to map the brain Tuesday, President Obama repeated a statistic he had used in the State of the Union addressone that we had been meaning to examine more closely.

Certainly, the presidents broader point is correctfederal government investment in research is often an important factor in innovations and scientific achievements that have enhanced Americans lives. But 140 times return on investment? That sounded a bit too good to be true.

Lets dig deeper into the data.

The Facts

The presidents factoidwhich he has asserted without citing a sourcecomes from a 2011 study by the Battelle Memorial Institute titled Economic Impact of the Human Genome Project: How a $3.8 billion investment drove $796 billion in economic impact, created 310,000 jobs and launched a genomic revolution.

Read more from the original source:
A 1 to 140 ‘return’ from the Human Genome Project?

Public release date: 2-Apr-2013 [ | E-mail | Share ]

Contact: Steve Yozwiak syozwiak@tgen.org 602-343-8704 The Translational Genomics Research Institute

KYOTO, Japan April 2, 2013 The scientific benefits of whole genome sequencing at the Translational Genomics Research Institute (TGen) will be presented at the 14th International Myeloma Workshop, April 3-7 at the Kyoto International Conference Center.

Dr. Jonathan Keats, head of TGen's Multiple Myeloma Research Laboratory, will present Discovering the Underlying Genetics of Multiple Myeloma Through Whole Genome Sequencing at 8:15 a.m. (Kyoto time) April 4, following the conference opening talk.

Multiple myeloma is a pathological description of a disease characterized by the accumulation of plasma cells in the bone marrow. Dr. Keats' lab at TGen is focused on using new methods to investigate the genomic features of this disease with the goal of identifying genetic events that drive the development, progression, and mediate therapeutic resistance.

"We will show for the first time the integration of DNA and RNA sequencing in multiple myeloma, and how TGen's comprehensive approach to this research has begun to uncover possible genetic changes that could lead to the underlying causes of this cancer," Dr. Keats said.

Previous studies have identified as many as 10 distinct biological subgroups of multiple myeloma, highlighting the need to identify distinct genetic defects to address each subtype of this disease.

Recent advances in next generation sequencing can now identify nearly all genetics events existing in an individual tumor. Initial studies have focused on whole genome sequencing or exome sequencing and confirmed genetic mutations (TP53, NRAS, KRAS) as well as identified novel mutations (FAM46C and DIS3). In addition, identification of recurrent BRAF mutations and the availability of targeted BRAF inhibitors provide an opportunity to translate research findings into clinical practice to benefit patients.

Dr. Keats is one of the key researchers in TGen's Multiple Myeloma Genomics Initiative, funded by the Multiple Myeloma Research Foundation.

"We will present results from the multiple myeloma genomics initiative using paired whole genome and transcriptome sequencing on 84 patient samples and 68 cell lines. The combination of DNA and RNA based sequencing approaches has improved our ability to identify biologically relevant alterations within each sample," Dr. Keats said.

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TGen professor discusses benefits of whole genome sequencing in study of multiple myeloma