MAR 11, 2015 4:35 PM PDT

Blood-based Genetic Biomarkers Identify Young Boys with Autism

WRITTEN BY: Ilene Schneider
In a study published in the current online issue of JAMA Psychiatry, an international team of scientists, led by researchers at the University of California, San Diego School of Medicine, report finding a highly accurate blood-based measure that could lead to development of a clinical test for autism spectrum disorder (ASD) risk in males as young as one to two years old. The test could be done in community pediatric settings. The degree of accuracy, they said, out performs other behavioral and genetic screens for infants and toddlers with ASD described in literature.

The causes of ASD are complex and diverse, making it difficult to conclusively diagnose the disease much before a child's fourth year of life. Indeed, the median age of diagnosis in the United States is 53 months.

"A major challenge is the difficulty of accurately diagnosing ASD, which is very heterogeneous, at an early enough age to implement the most effective treatment," said principal investigator Eric Courchesne, PhD, professor of neurosciences and director of the Autism Center of Excellence at University of California, San Diego School of Medicine.

In the proof-of-principle study, Courchesne, first author Tiziano Pramparo, PhD, and colleagues identified blood-based genomic biomarkers that differentiated toddlers with ASD, ranging in age from one to four years old, from a control group of toddlers without ASD. Blood samples were taken at the child's initial clinical intake. Importantly, the control group consisted of a mix of young boys commonly seen in community clinics, with typical development, mild language delay, transient language delay and global developmental delay. Against this control group, the researchers identified a genetic signature that identified 83 percent of ASD toddlers.

The study used an unbiased systems biology-based method to search for genes and gene pathways in blood samples that best distinguished ASD infants and toddlers from typically developing toddlers and toddlers with non-autism developmental delays. Specifically, the researchers measured leukocyte (white blood cell) RNA expression levels.

"Ideally, biomarkers come from tissue affected, but in ASD this is the brain, which is obviously an inaccessible tissue," said Courchesne. "Peripheral blood of living ASD infants and toddlers is an important alternative, and obtaining blood samples is routine and safe and, thus, is a preferable and accessible tissue for identifying signatures of ASD that could be used in clinical screening and follow-up evaluations."

Pramparo, an associate research scientist at the UC San Diego Autism Center of Excellence, said blood is expected to carry autism-relevant molecular signatures that can be used to detect the disorder at very young ages. It might also reflect aspects of the disrupted biology underlying neural defects.

In fact, the researchers found gene expression differences between ASD and non-ASD in genes related to translation and immune/inflammation functions, as well as cell adhesion and cell cycle. These "ASD signature classifier" genes are among those that can have effect on early brain development.

"New studies point to autism beginning in the womb," said Courchesne, who, with colleagues, published one such widely reported study last year detailing disrupted brain development in post-mortem brains of autistic children. "Our present study shows examination of the gene expression profiles at the very early age of initial clinical detection reveals both strong evidence of early biological processes in ASD and abnormal signals with the potential to serve as an early, practical biomarker of risk for the disorder in general pediatric settings."

The scientific team conducted two different analyses of blood samples involving two cohorts of study participants: 147 toddlers (91 with ASD, 56 control) in the first group, 73 toddlers (44 ASD, 29 control) in the second group. The first assay identified an ASD genomic signature 83 percent of the time; the second had a 75 percent accuracy rate.

Young male toddlers with autism were the focus of the study because autism is far more prevalent in males. "The genetics and molecular bases of autism may differ somewhat in affected males and females," said Pramparo. "We reasoned, therefore, that different signatures might need to be discovered and developed in each gender in ASD."

It was simpler to begin with boys. "Autism is four times more common in males," said Courchesne, "and so we were able to more quickly recruit and test samples of autism males than autism females. Our current work is aimed at recruiting sufficiently large samples of females to begin work to discover possible gene expression markers for them."

Courchesne emphasized that this was a first step toward a possible means of diagnosing autism much earlier than current methodologies, one that would greatly boost the efficacy of intervention and remedial treatments.

Though only proof-of-principle, Courchesne said the findings are encouraging. Next steps involve further refinement of the process and identification of diagnostic risk markers for females.

"As we write in the paper, our study showed that a blood-based clinical test for at-risk male infants and toddlers could be refined and routinely implemented in pediatric diagnostic settings."

Source: UC San Diego
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
You May Also Like
FEB 02, 2020
Genetics & Genomics
FEB 02, 2020
Ranking the Importance of Genes to Find Rare Disease-Causing Mutations
A team of scientists has classified genes according to how necessary they are for the survival of an organism.
FEB 03, 2020
Microbiology
FEB 03, 2020
The Switch Controlling the Stage of a Common Parasite
The parasite Toxoplasma gondii is thought to infect from one-quarter to one-third of the global population.
FEB 13, 2020
Genetics & Genomics
FEB 13, 2020
A Very Unusual Virus is Discovered in Brazil
Researchers in Brazil have discovered a very unusual virus infecting amoeba in an artificial lake called Lake Pampulha in the city of Belo Horizonte.
MAR 02, 2020
Genetics & Genomics
MAR 02, 2020
DNA Replication Discovery May Lead to New Cancer Treatments
Researchers have learned more about DNA replication during cell division, and their insights may help create new types of cancer therapeutics
MAR 15, 2020
Genetics & Genomics
MAR 15, 2020
Insight Into Neuronal Growth and Memory Formation
Now scientists have learned more about the transport of mRNA in neurons, and the storage and formation of memories.
APR 03, 2020
Neuroscience
APR 03, 2020
Why Autism is More Common in Boys than Girls
Researchers from the National Institutes of Health (NIH) have identified how a change in a single amino acid may be linked to symptoms of autism. In partic
Loading Comments...