Why have the JBRF researchers chosen an "affected sib pair" strategy to identify genes for juvenile-onset bipolar disorder? What are its strengths?
This approach is thought to be the most powerful method to identify genetic markers for conditions such as bipolar disorder that are believed to be caused by multiple genes. Because it requires mapping the genes of approximately 500 to 600 affected siblings—full biological siblings—who both have early-onset bipolar disorder and their parents, researchers are immediately confronted with a daunting logistical problem - where do they find, and how do they reach such a large number of families with two or more affected children. It is this task that most often limits the progress of such genetic studies.
Why is this "affected sibling pair" approach such a powerful genetic tool?
This strategy examines DNA markers on every chromosome and targets those that are shared by both affected siblings more commonly than chance would predict. Since brothers and sisters are expected to share a marker from one parent 50% of the time, any significant increase above the 50% level would home researchers to a chromosomal region in which the shared marker might also contain a gene for a shared trait, in this case, bipolar disorder.
How do researchers typically find subjects for such studies, how long does it take, and what does it usually cost?
To recruit subjects, typically, researchers place advertisements in major newspapers or advertise on the radio—repeatedly—and set up offices with administrative staffs to field calls from people willing to participate. In the past, the ascertainment of 50 affected sibling pairs within one year's time would demand an extraordinary marketing effort, expenditure of funds, and would ordinarily take at least six to seven years to identify, screen and diagnose the requisite number of sibling pairs necessary to complete such an ambitious study.
How has JBRF been able to recruit over 400 families with multiple children (some with three, four, five, and six affected siblings) in such record time (ten months) at very little cost?
A fortuitous confluence of resources available to the JBRF Research Consortium has advanced the time-table for recruitment of the affected sib-pairs by at least half a decade—far ahead of what had been expected when the study was first planned. The resources that have brought so many affected families to the JBRF Research Website for screening and evaluation are:
1. The novel, interactive Internet screening program developed for the JBRF web site which allows parents to complete forms in their own homes, and provides researchers with a rapid method for screening and sorting large numbers of subjects. The information already gathered, including demographic and clinical data on 1,950 children, is automatically stored in a secure database, and has already yielded important insights--a fine-grained picture of the symptoms of the illness and how they develop in childhood.
2. The JBRF Web site (http://www.jbrf.org) prominently appears in Google searches directed to "childhood or juvenile-onset bipolar disorder". This site is invariably listed in the resource sections of books targeted to this audience, and by the marketing and outreach efforts sponsored by JBRF.
3. The JBRF Professional Listserv (a listserv for medical doctors treating children with the illness). Doctors are made aware of the studies and inform parents in their practices.
4. JBRF director of research, Demitri Papolos, M.D., lectures throughout the country, and often appears in the media where he directs parents to the JBRF web site. Recent media appearances include The CBS Evening News With Dan Rather, The Early Show, and NPR's Morning Edition.
5. The Bipolar Child Newsletter, sent electronically to an audience of over 20,000 subscribers, primarily composed of parents of children with bipolar disorder and the professionals who treat them. Each time this highly respected newsletter has published information about the JBRF genetic study, it has yielded responses from many families who email their desire to take part in the research effort. Over half of the currently enrolled subjects were recruited through this resource.
Now that the affected sib-pairs have been identified, what happens next?
Diagnostic interviews are conducted with parents by telephone, and their affected children are interviewed in-person or with the new real-time video conferencing technology, ISight, developed by Apple Computer. Blood samples are then drawn from parents and sibling pairs and are sent by overnight courier to a molecular/genetics lab at the Albert Einstein College of Medicine. The DNA is extracted from white blood cells and then immortalized in cell lines to be later harvested and used whenever needed for genotyping purposes.
How will the genotyping be done and the data analyzed?
Once the DNA is immortalized, a genome-wide screening will begin. JBRF has established a relationship with deCODE, a company headquartered in Reykjavik, Iceland that will perform the genotyping. DeCODE operates the largest and most advanced high-throughput microsatellite genotyping facility today. Dr. Jurg Ott, chief of the Laboratory of Statistical Genetics of Rockefeller University and one of the world's leading statistical geneticists and Dr. Josephine Hoh, research assistant professor also at Rockefeller University, will conduct the statistical analysis.
Will the JBRF Research Consortium make this important resource available to other research groups?
The more research groups involved in looking for the genetic variations associated with juvenile-onset bipolar disorder within this important DNA archive, the faster our goal will be achieved. DNA samples will be made available to other research groups to enable them to join us in these critical efforts and to hopefully replicate and confirm positive findings.
Finding the genes that are responsible for early-onset bipolar disorder is the surest route to determining the underlying causes of the illness and will be a major step towards identifying new treatments that work at the root cause of the illness.
The Juvenile Bipolar Research Foundation continues to seek families
throughout the nation who have two or more children diagnosed with
early-onset bipolar disorder. If you would like to know more about this
study, please contact Janice Papolos at email@example.com.