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Why Do We Want To Find the Genes? While it is common-knowledge that we “are” the expression of our genetic makeup, within the last decade scientists have made remarkable new discoveries as to what those genes actually are and how they work. The picture is far more complicated than previous generations imagined. The four basic components of our DNA are repeated over and over again, approximately three billion times, in a seemingly endless variety of sequences that create our 20-30 thousand genes, which, in their entirety, compose the human genome. Of these three billion pieces of DNA, 99.9% of them are identical in every person. Only 0.1% of our genome is responsible for all of our genetic differences. Some of those differences are easy to detect such as hair color and height, while others are harder to quantify or describe such as those that confer disease susceptibility. While the messages of some genes may result in a discernable, “finished” product, many other genes function to regulate and give instructions to other genes; to turn them on or off, prompt them to make one product or another, make them more or less susceptible to other biological signals, or to effect the timing of expression. The range of gene structure and interaction is matched only by the range of possible gene variations and mutations. This degree of complexity poses a daunting problem for the scientists who search for disease susceptibility genes. However, there is good reason to be optimistic, as much groundbreaking information has already been discovered. The mapping of our human genome brought about an extraordinary turning point in genomic research. Scientists have determined the order of all three billion DNA base pairs that make up our DNA’s linear construction. They have begun to understand how that chain is differentiated into our many genes and have identified the purposes and effects of some disease susceptibility genes. As this picture becomes clearer investigators will be able to find the genetic variations at the root of an illness and thereby reveal clues that will point to far more precise treatments that target more specifically the causes of illness. The fervent hope is that this next generation of treatments may bring the relief that hundreds of thousands, perhaps millions, of families have been waiting for so desperately. Finding The Genes For Pediatric Bipolar Disorder (PBD) Finding the genes that are responsible for PBD is a major priority for the JBRF. While variations in single genes trigger the onset of some illnesses, such as cystic fibrosis, scientists have come to understand that variations in multiple genes trigger the onset of complex diseases such as bipolar disorder. Since 2001, JBRF has supported research which, amongst other things, will improve the chances of conducting meaningful genetic studies that will identify the group of susceptibility genes for PBD. Until recently, progress in the hunt for susceptibility genes for major psychiatric illnesses has been slow and fraught with many false starts. Now, however, there is a powerful technique called “genome wide association study” (GWAS) that allows investigators to scan the entire genome to look for problem genes. Already, this approach has yielded significant findings regarding inflammatory bowel disease, macular degeneration and susceptibility for certain types of breast cancer. The technique utilizes a “case control” design. That is, DNA obtained from a group of individuals with symptoms of an illness (cases) is compared to DNA obtained from a group of individuals who do not display the illness (controls). Genetic variations that are found to be more frequent in the cases as compared to the controls are said to be “associated” with the disease. These DNA variants pinpoint the precise location in the genome where the actual disease-causing genes may be found. However, there are several conditions that must be met in order for those variants to be significant and relevant and for the results to be replicable. The sample sizes must be very large. Recent studies on schizophrenia and the adult form of bipolar disorder show that the number of subjects needed to detect a statistically significant increase in genetic markers in a population of individuals with a complex disorder will require at least 1000 cases and an equal number of controls. Additionally, it is important that the nature of the symptoms of those individuals selected to be part of the case group be as similar to each other, in regards to the illness, as possible. In this way their DNA will, in essence, speak as one variant voice and enhance the likelihood of identifying specific vulnerability genes for the illness rather than bring attention to variations that are actually random and misleading. Replication of results is the gold standard of a meaningful study. If the results cannot be replicated, that is a strong indication that the results actually were random and the group of “case” DNA was not defined accurately enough. We believe that the research supported by JBRF addresses both of these requirements sufficiently. The availability of data from more than 6,000 families enriched with bipolar disorder has provided JBRF with a unique opportunity to analyze clinical and behavioral data on what is the largest sample of youth diagnosed, with or at risk for, BPD in the world. From this study, a highly refined set of symptoms associated with a specific genetic trait of the illness has been established. We believe that this core complex not only identifies the illness in an accurate and important way, but simultaneously creates a diagnostic category of the illness that brings a large number of children into a homogeneous grouping. Individuals who meet that profile can be identified with 96% accuracy. Further, recruitment of those individuals through a portal in our website promisCollecting the DNA: We Need Your Help es to gather the large number of subjects needed for a genome study. Collecting the DNA: We Need Your Help The collection of DNA for the genome-wide scan is currently under way. While we are fortunate to have a substantial number of samples already gathered, there is a strong need to collect more. While so much of what goes on in pediatric bipolar disorder feels beyond control, here is an opportunity to directly be part of a promising step towards the solution. We particularly urge families with multiply affected individuals (between or within generations) to consider participating as the heritable aspects of the illness are stronger in these lines. If you are interested in participating, it is pain free. DNA can now be collected in saliva rather than blood; an improvement that is particularly appropriate for this population of children whose sensory sensitivity almost universally includes needle phobia. Here’s what you can expect if you choose to participate: 1. You would begin by answering some very basic introductory questions and then completing a standardized assessment called the Child Bipolar Questionnaire (CBQ) on the JBRF website. (You can learn more about the CBQ by clicking here.) 2. Families whose children meet the study criteria will be contacted for further evaluation. After you provide Informed Consent, a research assistant trained in the use of the K-SADS P/L (a standardized diagnostic instrument) will administer this interview by phone, score the results and enter them in the database. Parent/s, surrogate/s and/or child will be interviewed. This interview will require 2-3 hours of time. Once all of this information has been gathered, a final expert opinion will be weighed as to the case’s diagnostic appropriateness for the study. 3. The final step will be to send out saliva sample collection kits to obtain DNA from parents and children. These kits will have prepaid postage and packaging and will be sent to the molecular/genetics lab of the Program in Behavioral Genetics at Albert Einstein College of Medicine where DNA is extracted and archived for genotyping (genetic analysis). To start your participation, click here. Working Together Bipolar disorder casts long shadows from one generation to the next. We know the distress of living with the disease. Science is now poised to interrupt that inevitability… even within this generation’s lifetime. The genetic variations that cause the disease to onset at a young age, while more devastating, offer the advantage of more clearly revealing the disorder’s underpinnings. While your participation might seem like only one small step, please understand that we can not do the study without your help. By working together we can make the difference. Participate. Share your information. Provide DNA if selected. Every contribution helps bring us closer to better, targeted treatments for our children and for our children’s children.
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New: Are you interested in finding out if your children qualify to participate in the JBRF's research studies? Learn more here. Context and Summary of JBRF Sponsored Research Clinical Phenomenological Study of Childhood-onset Bipolar Disorder Neuropsychological Testing in Juvenile-onset Bipolar Disorder
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