Are you lactose tolerant? If you’re of Northern European ancestry this is because of a stretch of DNA in a gene enhancer that developed some 9,000 years ago. That's the same time Northern Europeans began domesticating cattle for milk. If you’re of African ancestry, you may have one of three mutations which appeared independently of the European mutation--and of each other--about 6,000 years ago, again when dairying began.
The genetics around lactose tolerance are a great example of how diverse human populations evolved and how this diversity impacts our health. While many in our field are feeling chagrin at not being able to unlock more secrets in our biology that will lead to medical breakthroughs, some leading researchers are pointing to the need for more diversity in our genomic databases, with a particular emphasis on structural variation.
Sarah Tishkoff began studying African genetics back in graduate school on some cell lines that had been collected and started years before. It was at a conference in Cape Town, South Africa with other geneticists and archeologists and members of the local population where she was asked a question that began her career in Africa. Why are the populations up in Tanzania--those people who speak with clicks--so different from the people not far to the south? Sarah went to Tanzania to find out.
“I had no idea what I was doing at the time. I went to Tanzania and just did it. It was quite an experience going as a woman and leading a team of Africans who were just not used to working with a female leader.”
Since then, the dramatic improvement of sequencing technology has allowed Sarah and her team to do some groundbreaking genetic work, much of which has medical implications. For example, her research into the G6PD gene has shown that for certain African populations common malaria drugs can be toxic.
Because Africans are more genetically diverse and have the oldest genetic lineage, African genetics plays an important part in all human genetics research. It's important that our databases include this diversity. Sarah says the recent work to improve the human reference genome is “a great start” but there’s much more to be done. The three African genomes we pointed out in a recent program, she says, are actually from a common regional ancestor. They only reflect a fraction of the African diversity.
Sarah agrees with those in our field lately who have observed that there are still many mysteries in the genome which have not been unlocked because we’re missing important structural variants.
“I believe that some of these structural variants are going to be functionally super important. They’re going to impact normal variation and disease risk. If we had a more diverse set of reference genomes, then that would be great. People could then go ahead and use short read sequencing and map it back to all these diverse reference genomes. And that’s going to help people in terms of personalized medicine."