Global genetic variations unveiled

U-M scientists and their colleagues at the National Institute on Aging (NIA) have produced the largest and most detailed worldwide study of human genetic variation, a treasure trove offering new insights into early migrations out of Africa and across the globe.
Researchers are tracking worldwide human genetic variations, as illustrated in Africa. (Photo by Martin Soave/Michigan Marketing & Design)

Like astronomers who build ever-larger telescopes to peer deeper into space, population geneticists like Noah Rosenberg are using the latest genetic tools to probe DNA molecules in unprecedented detail, uncovering new clues to humanity's origins.

The latest study characterizes more than 500,000 DNA markers in the human genome and examines variations across 29 populations on five continents.

"Our study is one of the first in a new wave of extremely high-resolution genome scans of population genetic variation," says Rosenberg, an assistant research professor at the Life Sciences Institute and co-senior author of the study, published in the Feb. 21 edition of Nature.

"Now that we have the technology to look at thousands, or even hundreds of thousands, of genetic markers we can infer human population relationships and ancient migrations at a finer level of resolution than has previously been possible."

Worldwide assessment

The new study, led by Rosenberg and NIA colleague Andrew Singleton, produced genetic data nearly 100 times more detailed than previous worldwide assessments of human populations. It shows that:

• A recently discovered type of human genetic variation, known as a copy-number variant or CNV, is a reliable addition to the toolkit of population geneticists and should speed the discovery of disease-related genes. Rosenberg and his colleagues discovered 507 previously unknown CNVs, which are large chunks of DNA — up to 1,000,000 consecutive letters of the genetic alphabet — that are either repeated or deleted entirely from a person's genome;

• It's sometimes possible to trace a person's ancestry to an individual population within a geographic region; and

• Human genetic diversity decreases as distance from Africa-— the cradle of humanity — increases. As a result, searching for disease-causing genes should require the fewest number of genetic markers among Native Americans and the greatest number of markers among Africans.

The results are being made available on publicly shared databases.

'Serial founder effects'

The researchers analyzed DNA from 485 people. They examined three types of genetic variation: single-nucleotide polymorphisms (SNPs), haplotypes and CNVs.

If the human genome is viewed as a 3-billion-letter book of life, then SNPs represent single-letter spelling changes, haplotype variations equate to word changes, and CNVs are wholesale deletions or duplications of full pages.

The patterns revealed by the new study support the idea that humans originated in Africa, then spread into the Middle East, followed by Europe and Asia, the Pacific Islands then to the Americas.

The results also bolster the notion of "serial founder effects," meaning that as people began migrating eastward from East Africa about 100,000 years ago, each successive wave of migrants carried a subset of the genetic variation held by previous groups.

"Diversity has been eroded through the migration process," Rosenberg says. In addition to his position at the Life Sciences Institute, Rosenberg is an assistant professor of human genetics, biostatistics, and ecology and evolutionary biology, as well as an assistant research professor of bioinformatics.

"This data set is so rich. It provides a much more comprehensive, cross-sectional snapshot of the human genome than previous studies," says Paul Scheet, author and post-doctoral researcher in the Department of Biostatistics.