Today’s Hutterites live and work together, sharing the same food and resources, so there is little environmental variation between individuals. They also descended from the same small group of founders, so they provide a perfect population for studying genetic variation and disease inheritance. Carole Ober, PhD, Blum-Riese Professor of human genetics, and her colleagues have been doing just that for decades, studying the Hutterites (PDF) to learn more about the roots of common disease. After decades of work, you’d think they would have learned everything there is to know about this unique society, but a new study using genome-sequencing tools found that there’s still a lot to learn.
The study, published in the American Journal of Human Genetics, looks at the prevalence of autosomal-recessive disease-causing mutations in more than1,600 Hutterites from South Dakota. These are mutations in a gene on one of the 22 non-sex chromosomes (i.e. not the X or Y chromosome that determines a person’s sex). Both parents have to carry a copy of such a mutation for their child to be at risk of developing an autosomal-recessive disorder such as cystic fibrosis or Tay-Sachs disease.
Given what researchers know about the number of such mutations that an average person carries, or their carrier burden, they can calculate the expected number of mutations that are passed on to descendants – aware, of course, that some mutations are lost over time through a random process called genetic drift.
In this study, researchers screened the genomes of the Hutterites for 14 different autosomal-recessive disease-causing mutations. Some of the mutations had fairly high carrier frequencies, that is, proportion of the group that carries the mutation, while others were very rare. However, based on simulations using the genealogical records of the group, researchers predict that their current average carrier burden is lower than in the founders of the group, meaning the Hutterites today carry fewer mutations than their founders. Yet today’s Hutterites may carry at least 30 more mutations that haven’t been reported.
Jessica Chong, a graduate student in Ober’s lab who was one of the authors of the study, said, “We are very interested by our simulations that show that even though we know a lot about recessive disorders in the Hutterites, there could be an equal or greater number of disorders no one has even heard of yet.”
This means that as genetic sequencing techniques improve, continued studies could help identify such unknown diseases and guide future treatments. The stable, isolated population of Hutterites provides a nice laboratory to explore this possibility.
Chong said there are a couple of explanations for those undiscovered diseases. A disease could be so mild that it doesn’t present outward symptoms. It could also be worse, when a disorder is so severe that it causes a miscarriage early in pregnancy before anyone finds out.
And, she said, there’s also the element of chance that makes some rare disease mutations disappear and others hide until the right two people meet. Despite decades of research there’s still the chance that the Hutterites can teach us something new.
Chong JX, Ouwenga R, Anderson RL, Waggoner DJ, & Ober C (2012). A population-based study of autosomal-recessive disease-causing mutations in a founder population. American journal of human genetics, 91 (4), 608-20 PMID: 22981120