Apr. 25, 2002 Using a unique set of data collected over 30 years and six generations of captive-bred monkeys, researchers have found the first evidence that low birth weight is linked to a type of DNA only passed along by females.
"This is why, when it comes to birth weight, we tend to be more like our mother than our father," said James Ha, a University of Washington research professor of psychology and lead author of a study published in the current issue of the American Journal of Primatology. The National Institutes of Health funded the research.
"We definitely think that our findings will hold up when human data becomes available," he said. "Some people have suggested that birth weight in a number of species including humans is closer to the mother than the father. But there never has been adequate data to test a hypothesis of cytoplasmic DNA inheritance. Instead, human research has focused on environmental causes."
While the new study links maternal genetics to low birth weight, it does not mean pregnant women should ignore known environmental risk factors such as alcohol, drugs and a poor diet that contribute to the birth of underweight babies. Ha said that there is more than one type of DNA, or deoxyribonucleic acid, the material in cells that carries the genetic code and transmits hereditary traits.
"People tend to look at DNA as only being inside the nucleus of a cell. However, there also is DNA in the cytoplasm that surrounds the nucleus inside the cell membrane. Some of this DNA is found in mitochondria."
Mitochondria are structures that are the so-called "powerhouses" that control energy production in cells and mitochondrial inheritance is only passed along to offspring by the mother. He said the connection between how much energy is produced and low birth weight "makes so much sense."
Ha calculated that cytoplasmic DNA from mitochondria is responsible for 9 percent of the variability in birth weight, while traditional nuclear DNA accounted for an additional 42 percent of the variability. This suggests there may be a gene or genes that control birth weight.
"The next step is to find which gene or genes are responsible and what pathway controls this process. We also need to look for links between genetic effects of low birth weight and other factors that endanger children such as low IQ," he said.
"We want to know why birth weight is a risk factor for other perhaps more critical things. One possibility is that there is a gene that affects birth weight, and the same gene controls IQ, retardation and memory difficulties. That gene has two effects, but we don't know if there is a direct or indirect connection. We believe there may be a genetic component in common, and if we can identify the genes and the mechanism we then can explore why children are at risk."
The study is based on data from six generations, extending out to fourth cousins, of pigtailed macaques (Macaca nemestrina), a type of Old World monkey, and includes the pedigrees of more than 12,000 animals.
"You need to have this kind of broad data from the extended family to determine the subtle effects of mitochondrial DNA," said Ha. "No one has clean data from human studies because of environmental factors such as smoking, drinking and narcotics and because everyone has a different diet."
Researchers are interested in understanding the causes of low birth weight because it is known to affect mortality rates among human newborns. In addition, nearly half of low birth weight children will have some form of physical, cognitive or emotional impairment, and new evidence suggests it also contributes to adult illnesses such as diabetes, heart disease and hypertension.
In the study, Ha and his colleagues used data collected between 1967 and l996 at the Washington Regional Primate Research Center operated by the UW to analyze the birth weight of more than 3,500 pigtailed macaques born in non-experimental pregnancies. The animals are native to Southeast Asia and newborns typically weigh between 380 and 620 grams (about 15 to 24 ounces). Low birth weight animals, the lowest 10 percent, weigh 300 grams or less (12 ounces).
The researchers did find one environmental factor that influenced the birth weight of the animals – how mothers were housed in the last trimester of their pregnancies. The monkeys were either housed in a social group, which had the lower mean birth weight, or in individual cages. The housing environment explained 6 percent of the overall variance in birth weight. Overall, data from the study suggests that there is a roughly 50-50 split between genetics and environment influencing birth weight.
Co-authors of the study are Renee Robinette Ha, a UW lecturer in psychology; Laura Almasy, staff scientist at the Southwest Foundation for Biomedical Research in San Antonio, and Bennett Dyke, director of population genetics at the Southwest Regional Primate Research Center in San Antonio.
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