Circumventing the inheritance of genetic defects passed down from mothers to offspring is the subject of research soon to be conducted at Fresno State by Dr. Joseph A. Ross, assistant professor of biology.


He recently received an Academic Research Enhancement Award (AREA) grant from the National Institutes of Health. It will support the work of three undergraduate students at a time, who will be trained during December so they can begin their research study next semester and continue over three years.


The scientific question under study is whether it is possible to control the normal inheritance of mitochondria to allow paternal inheritance, which could provide avenues to develop approaches for avoiding the maternal inheritance of mitochondrial mutations, which can cause a number of human disorders affecting key areas of the body, such as the eyes, the muscles, and the heart.


Mitochondria, classically known as the powerhouses of the cell, produce cellular energy in the form of a molecule called ATP. They must function properly to conduct this critical life process that is essential to good health.


Numerous diseases are attributed to mutations in the mitochondrial DNA, including diabetes mellitus and deafness (DAD), Leber's hereditary optic neuropathy, and Leigh syndrome, a severe neurological disorder.


"In most species [that have mitochondria], the mitochondria are inherited only from the mother," said Dr. Ross. "Our immediate aim is to try to figure out what genes and proteins are involved in letting cells distinguish which mitochondria are mom's and which ones are dad's. Right now, we don't know. Lots of research has to go into our understanding of how mitochondrial inheritance works."


About a decade ago, scientists realized there might be a way to circumvent the process of maternal mitochondrial inheritance through three-parent fertilization. The process substitutes a third-party's egg from a female donor without mutant mitochondria for fertilization; its genetic material is removed so that the parents' DNA can be used.


But such an approach raises ethical issues, such as donor privacy and parental rights. Dr. Ross is looking at another solution.



His research proposes to find out whether selecting for retention of a father’s mitochondria can prevent the inheritance of the mutations in maternal mitochondrial DNA.

"The basic question we're interested in is how is it that an oocyte, or egg, at fertilization knows how to identify and destroy all of dad's mitochondria," he said. "There are thousands of mitochondria at fertilization when that embryo cell is formed. And we suspect that that's the time when dad's mitochondria are all destroyed, causing maternal-only inheritance of mitochondria."


Looking at species that don't follow a pattern of strict maternal inheritance, such as some species of worms, can provide clues to how paternal mitochondria might be passed on to offspring.

"We have a natural case where we see dad's mitochondria getting in," Dr. Ross said. "We're wondering — broadly, in the three-year project we have — if we can figure out how to manipulate the worms so that dad's mitochondria are the only mitochondria that get into the oocyte, and mom's don't."


The data gathered by this research might be very useful in cases in which a woman has mitochondrial mutations she does not want her children to inherit.


"If we can learn how the oocyte, or egg, targets and destroys dad's mitochondria, we can turn that system off, so that dad's mitochondria can get into the offspring," Dr. Ross said. "That could be beneficial. Maybe down the line — ten, twenty, fifty years — we will have enough ground research to determine whether that's useful and whether it has any side-effect in humans."


The implications of the Fresno State study could have a profound effect on the forefront of genetics research, but perhaps even more importantly, the study helps train future scientists to investigate multiple paths of treatment.


For Dr. Ross, it all boils down to doing what he loves most.


"The reason I wanted to be here at Fresno State is the balance of research and teaching," Dr. Ross said. "I love doing both — mentoring students and doing research."