Genes May Imprint Birth Stats

While cloning cows at Texas A&M several years ago, Dr. Jorge Piedrahita noticed that very few of the cloned animals could later reproduce. Cloning somehow disrupts the normal development of the placenta, says Piedrahita, now a professor of molecular biomedical sciences at NC State’s College of Veterinary Medicine. That discovery spawned his fascination with placental function and the critical role a tiny subset of genes, called imprinted genes, plays in animal and human development.

“Researchers have identified fewer than 100 imprinted genes in humans, but they have been implicated in a range of illnesses, from diabetes to Alzheimer’s to alcoholism.”

Found only in placental mammals, imprinted genes are expressed differently in the paternal and maternal DNA handed down to offspring. Also, unlike other genes that rely mostly on the DNA sequence to function, they are regulated by conformation, or how tightly packed the genetic material is within cells. Researchers have identified fewer than 100 imprinted genes in humans, but they have been implicated in a range of illnesses, from diabetes to Alzheimer’s to alcoholism.

As part of a five-year National Institutes of Health grant, Piedrahita is working with OB-GYNs at Duke University Medical Center to monitor women during at-risk pregnancies and collect samples from their placentas after birth for study. Babies whose birth weight is in the eighth percentile or lower have been shown to be at higher risk for diseases as adults. So he is conducting genomic analyses on the tissue samples, while Dr. Dahlia Nielsen in the Bioinformatics Research Center does a quantitative study to correlate imprinted genes, clinical data from the mother during pregnancy—factors like age, diet and exposure to chemicals—and fetal development and birth weight. “You have to go beyond the genes responsible for growth to a systems focus because the effects of imprinted genes are so complex,” Piedrahita says. “Too many factors can cause a baby to be small. You can’t just say, ‘This is it.’”

In animals, imprinted genes may affect the size of litters. Working with the USDA Meat and Animal Research Center, Piedrahita is providing a genetic analysis of placentas in two breeds of pigs. He has determined that a key metabolic pathway is regulated differently in the placentas of an Asian breed and a commercial breed. That allows the Asian breed to produce 14 to 16 piglets in a litter, compared to 9 to 12 for the commercial breed. But he still is figuring out how imprinted genes regulate that pathway. “These genes play such an important role in human disease and agriculture production,” he says, “They will provide a research challenge for the rest of my life.”

 

Dr. Jorge Piedrahita and CVM Assistant Research Scientist Lauren Gast discuss their research efforts.

Dr. Jorge Piedrahita and CVM Assistant Research Scientist Lauren Gast discuss their research efforts.

Green cells indicate normal process of apoptosis (cell death) and development in a normal pig placenta.

Green cells indicate normal process of apoptosis (cell death) and development in a normal pig placenta.

Placental cells
from pig with abnormally imprinted genes show a lack of or
delay in apoptosis.

Placental cells from pig with abnormally imprinted genes show a lack of or delay in apoptosis.