A new technique that generates high-resolution images of the genome and liver of black and white newborns at birth has identified another genetic mutation linked to the higher rate of death in these infants in the first few years of life. The technique also could be adapted to detect preterm births among white infants born in the United States, researchers said. The results are published in Nature Biotechnology.
The study led by the lab of Richard Levy, MD, Director of the Weizmann Institute of Science, focused on a particular genetic mutation that previously was associated with multiples thyroid cancer diagnoses in African American infants and development delayed thyroid function.
“For our study, we compared gene expression profiles of the liver tissues of 50 black pups and 40 white pups for this mutation. Twenty-four of the sample showed significantly higher expression of the gene for the gene that encodes the transcription factor TRIM36, which helps with the regulation of the function of the fetus—creating a maternal reserve to protect against severe myelogenous leukodystrocytosis, a commonly occurring hereditary autoimmune disorder of the adult body,” said Levy, who is also an Associate Professor of Dermatology at Harvard Medical School.
Liver cells produce the neurotransmitter serotonin, and the TRIM36 gene provides the protein for the production, along with other genes that interact with it. There are only four copies of the TRIM36 gene and the gene must be passed on through both parents. The experiments used by the team involved assaying for congenital disorders in pregnant women, which caused poor placental function with birth weight, with spontaneous abortions and with Tanner stage infants.
“This study will strengthen the statistical tools of the multidisciplinary research community, allowing us to better understand the genes of long-term health and disease among populations such as African Americans in whom we were previously unable to show such a large genetic association,” said Levy. Of the tracking, global gene activity was measured across the entire genome and liver region.
Of the 50 normal pups, only one (2 of the 47) contained gene expression that was significantly higher than in white congenital pups of the same DNA sequence. The authors noted that another consistent interpretation of the nature of genotype is that within the 25-gene region of chromosome 6, dominant-negative c-myc and dominant-positive c-myc are all induced by TRIM36 gene expression.
Levy said, “Another interesting finding is that despite having a normal TRIM36 gene expression pattern we now have a congenital disorder for which the gene did not express the correct expression pattern. In essence, we have found another genetic cause linked to cellular function and this type of disorder has not been documented before.”