The Search for a Rare Genetic Disease: International Collaboration in Laboratory
and Field Research. Gary L. Robertson, MD. Northwestern University, Chicago, IL USA
Since genetic variation is responsible for individual differences in many physical and
mental traits, it must also be responsible in part for cultural diversity. This influence may
be investigated by modern methods of genetic analysis. Some principles of this approach
are illustrated by a recent project to determine the cause and genetic basis of an
apparently unique disease discovered in a Swedish family over 60 years ago. The disease,
known as diabetes insipidus (DI), is characterized by the production of abnormally large
volumes of urine. In this family, it affects only males and was thought to be due to a
hormone deficiency. However, the pattern of transmission is like another type of DI
known to be caused by hormone resistance. The project aimed to resolve this uncertainty
by finding the descendants of the family in Sweden and testing them with modern
methods of clinical diagnosis and genetic analysis. After a long search, 15 descendants
were located and tested. The males all turned out to have the type of DI caused by
hormone resistance and the cause was traced to a tiny mutation in the gene on the X
chromosome that makes the hormone receptor. Other small mutations in this gene cause
the same type of DI in the males of many other families worldwide. Thus, the genetic
variation responsible for a large difference in a biological trait can be very small,
extremely diverse and widely distributed.
