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One-on-One with Pardis Sabeti
By Lango Deen
Jul 25, 2005, 08:59

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Pardis Sabeti earned her master's degree in human biology, and her doctorate in biological anthropology at The University of Oxford as a Rhodes scholar where she specialized in genetic diversity and contributed articles to Encarta Africana, Genes and Immunity and Nature. She will shortly complete her M.D. at Harvard Medical School, and plans a career in academic medicine and research. Sabeti was born in Iran in 1975. She arrived in the US at age 2 and now resides in Orlando; Fla. Sabeti plays guitar and bass and is the lead singer of a rock band.


SS: How does your research relate to the Human Genome Project?


Sabeti: The human genome initiative is the foundation on which my research is based. Through the genome project, they identified the blueprint of the genome, the 3-billion nucleotide bases on 23 chromosomes that make up the genome structure. Once that blue print was done, it was possible to go back and find out all the variations that exist in human populations.  The genome project has opened the door to studying human variation as well as numerous other aspects of the genome. 


All humans are very much alike. They have the same heart, the same skin, the same eyes, and this is all because in general, 99.9 per cent of DNA in their genomes is shared between people. But once that information was known about the general structure of human genes and the human genome, we could begin studying the 0.1% of the genome that varies between people. Why different people have blue eyes and some people have brown eyes? What are those small changes that exist in the human genome that cause these things?  So, once human genome initiative was done, we moved on to finding the DNA variations that exist in the human genome.


That is what has made possible my research, which studies natural selection in the human genome. The work I do looks at all the different variations that exist in populations and tries to investigate the ones that have an interesting history. So these variations, these small changes in our DNA, are distributed throughout the 3-billion nucleotide bases in our genome. In my research, I have developed a method to measure how long ago each of these variations arose, to determine how old they are. So we can then look at these variations and ask are any of these variations common in human populations such as lots of people having brown eyes but look young. The signal of something evolving from natural selection is a variation that is common, but too young to have gotten to its high prevalence in the population by chance alone.  For example, the sickle cell mutation - the mutation that causes sickle cell anemia - which is a very bad anemic blood disorder in humans - is very common in Africa, and is caused by one single change in DNA. But it is interesting in that it very prevalent in Africa. About 20-30 per cent of the population have the variation, but if you look at how old that mutation is, it is really quite young, relatively very young.


And so once the variation arose, it spread very quickly in human populations. The reason why having this small variation in DNA that affects your blood would spread so quickly is that it appears to protect from getting get an infection from malaria, or, d[ying] from malaria.  So it is very advantageous for people who have it in regions where the burden of malaria is high. People with variation would have a greater chance of surviving to reproductive age and have children. And they would pass their DNA on to their children. We could see many variations in the human genome that are likely to have experienced this kind of rise to prevalence through natural selection. 


SS: What are the challenges of working with the human genome?

Sabeti: The raw amount of data you�re dealing with. Right now we�re looking at 1, 0000,000 changes in 300 different individuals. Millions of data points we�re trying to analyze.  And with that kind of information, {the challenge is] getting it down in an understandable way, and representing it in a way in which we can understand what�s going on. And with so much data, we have to be careful to distinguish the signals of natural selection that are real from those that may not be.  It�s both a challenge and an opportunity. Because now you can see the human genome all at once, you can begin to see what is interesting and what stands out from the rest of the genome. It�s more of a real opportunity for geneticists to challenge the tests we�ve already done.


SS: What are the business opportunities?


Sabeti: In essence, what my work is to point out all of the genes, and all of the particular changes in the genes that have helped humans throughout human history. Those that protect us from infectious and other disease, that increase our ability to reproduce; and that in other ways help to increase our survival.  All of these genes that we�re finding are just the first step towards understanding how human variations protect us. Once we uncover these underlying beneficial variations that have helped our survival throughout human history, we can begin to think how we can replicate their actions through science.

Dr. Sabeti was one of the first five recipients to receive the annual L�Or�al USA for Women in Science Fellowship. In 1998, L�Or�al  decided to partner with UNESCO (the United Nation Educational, Scientific and Cultural Organization) in a program to highlight and recognize the contributions of eminent women researchers and to encourage promising young women scientists in advancing their careers through fellowships � that program is the L�OR�AL-UNESCO for Women in Science Awards and Partnership. L�Or�al USA will launch applications for the 2006 Fellowship Awards in August.

© Copyright 2004 by Career Communications Group, Inc.

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