The coincidence of high blood pressure and high cholesterol is too great to be attributed to chance, yet the underlying cause has long been unclear. But researchers at Yale and Syracuse universities may have demystified the mechanism for the correlation by studying the mitochondria — a part of the cell that had previously been overlooked.
The research team, led by Dr. Richard Lifton, chair of Genetics at Yale, investigated mitochondrial DNA as opposed to conventional nuclear DNA. The results showed a relationship between this DNA and inherited illnesses such as hypertension, high cholesterol and low magnesium.
The study evolved from the case of one woman who exhibited familial low magnesium levels. This discovery led to an increasingly involved analysis that included 142 members of a single family, Lifton said.
“[It was] extremely important because we could tell just from the pattern of inheritance in this family that the metabolic problems would prove to be due to the mitochondrial genome,” Lifton said.
The direction of the research after this observation moved toward the sequencing of the mitochondrial genome — some 16,000 base pairs as compared to the three billion base pairs of the nuclear genome — and resulted in the discovery of an unknown mutation, Lifton said.
An informal collaboration developed between Lifton and Dr. Steven Scheinman MED ’77, dean of the College of Medicine at SUNY Upstate Medical University. Scheinman initially began work with the family and turned to Lifton and Yale for further development of his ideas, he said.
Scheinman said the research is groundbreaking, and its results could have a great impact on medical knowledge of inherited diseases.
“It is very hard to discover a new mechanism in genetics,” Scheinman said. “When you find a gene not on anybody’s list, you learn a whole new aspect of physiology.”
Anita Farhi, a research specialist with Howard Hughes Medical Institute and a member of Lifton’s team, recruits subjects for the research protocols. She said this study strikes a rare balance between laboratory and clinical elements. Another positive aspect is that the study uses a human model to guide the research rather than relying solely on theory, she said.
Farhi and the team utilized a key characteristic of mitochondrial DNA — it is inherited only from the mother — to detect an interesting pattern within the data.
“There was a pattern of inheritance in that sons of mothers with low magnesium would have low magnesium and would not pass it on to their children,” Farhi said. “Mitochondrial disease is not particularly well characterized in humans.”
Lifton said the work will not be complete until researchers understand the system by which altered mitochondrial function relates to metabolic traits, characterize how other possible mitochondrial mutations affect inherited traits and explore the age-related loss of mitochondrial function.
“[We] now have genotype, phenotypes and a black box in between,” Lifton said.