Human genes transplanted into zebrafish: Helps identify genes related to autism, schizophrenia and obesity

ScienceDaily (May 16, 2012) What can a fish tell us about human brain development? Researchers at Duke University Medical Center transplanted a set of human genes into a zebrafish and then used it to identify genes responsible for head size at birth.

Researchers at Duke University Medical Center transplanted a set of human genes into a zebrafish and then used it to identify genes responsible for head size at birth.

Head size in human babies is a feature that is related to autism, a condition that recent figures have shown to be more common than previously reported, 1 in 88 children in a March 2012 study. Head size is also a feature of other major neurological disorders, such as schizophrenia.

“In medical research, we need to dissect events in biology so we can understand the precise mechanisms that give rise to neurodevelopmental traits,” said senior author Nicholas Katsanis, Ph.D., Jean and George Brumley Jr., MD, Professor of Developmental Biology, and Professor of Pediatrics and Cell Biology. “We need expert scientists to work side by side with clinicians who see such anatomic and other problems in patients, if we are to effectively solve many of our medical problems.”

The study was published online in Nature journal on May 16.

Katsanis knew that a region on chromosome 16 was one of the largest genetic contributors to autism and schizophrenia, but a conversation at a European medical meeting pointed him to information that changes within that same region of the genome also were related to changes in a newborn’s head size.

The problem was difficult to address because the region had large deletions and duplications in DNA, which are the most common mutational mechanisms in humans. “Interpretation is harrowingly hard,” said Katsanis, who is also director of the Duke Center for Human Disease Modeling.

The reason is that a duplication of DNA or missing DNA usually involves several genes. “It is very difficult to go from ‘here is a region with many genes, sometimes over 50′ to ‘these are the genes that are driving this pathology,’” Katsanis said.

“There was a light bulb moment,” Katsanis said. “The area of the genome we were exploring gave rise to reciprocal (opposite) defects in terms of brain cell growth, so we realized that overexpressing a gene in question might give one phenotype — a smaller head, while shutting down the same gene might yield the other, a larger head.”

The researchers transplanted a common duplication area of human chromosome 16 known to contain 29 genes into zebrafish embryos and then systematically turned up the activity of each transplanted human gene to find which might cause a small head (microcephaly) in the fish. They then suppressed the same gene set and asked whether any of them caused the reciprocal defect: larger heads (macrocephaly).

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(1) Human genes transplanted into zebrafish: Helps identify genes related to autism, schizophrenia and obesity
URL: http://www.sciencedaily.com/releases/2012/05/120516140012.htm



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