3 articles on genetics from the national psoriasis foundation
How Are Genes Involved in Psoriasis?
First posted Nov. 4, 2003
Genetics researchers at a recent meeting in Rome supported by the National Psoriasis Foundation suggest many of the genes that make people susceptible to psoriasis will be identified in the next several years. Gene discovery provides hope, but hope also requires understanding the next steps in the process and how these dicoveries may lead to improved treatments.
Genes control everything from height to eye and hair color. Differences between people result from different forms of the gene. Genes determine how cells act. When genes are working normally, the body and its cells function normally. When a misstep occurs in the way a gene works, disease may result.
When a specific gene is found to be linked to psoriasis, researchers will have to determine what the gene does in a "normal" setting. Then, they will have to determine how the gene is different and thus how it causes psoriasis. This is a very difficult and time-consuming process, because researchers know that more than one gene is responsible for causing psoriasis.
In fact, scientists believe that at least 10 percent of the general population inherits one or more of the genes that create a predisposition to psoriasis. However, only 2 percent to 3 percent of the population develops the disease.
This is thought to be because only 2 percent to 3 percent of people encounter the "right" mix of genetics and triggers that lead to the development of psoriasis. Those who have psoriasis but don't have a family history of it, for example, may have "inherited" two genes from their father and two from their mother-neither of whom had all four and therefore never developed psoriasis.
Genetics 101
Genes are essential for the body to perform the functions necessary for life. Every cell has 3 billion units of genetic material, called "deoxyribonucleic acid" (DNA).
DNA provides the information to direct the "synthesis," or making of, proteins.
Proteins are large molecules that perform a wide variety of very specific functions in the body. Out of all the DNA in our cells, only an estimated 30,000 proteins are produced. Genes are a unit of genetic material that code information for one protein. Therefore, researchers say we have approximately 30,000 to 40,000 genes. There are several possible genetic changes that could explain why psoriasis occurs.
The DNA that makes up the genes may have too many components. It may contain extra chemical pieces that make up DNA, which results in "faulty" proteins being made.
Some chemicals in the DNA could be in the wrong place or missing, which leads to the proteins being misshapen or not produced at all.
Some genes may be turned on or off at the wrong rate.
Once the genetic source of the disease is pinpointed, researchers will then be able to begin work on determining why some people get psoriasis and others don't. By understanding how people who develop psoriasis are genetically different than people who do not, scientists may be able to create treatments that "correct" the behavior of cells. Or, they may be able to fix this difference in the genes themselves.
Researchers Solving the Genetic Mystery of Psoriasis
First posted Nov. 4, 2003
As the saying goes, "Rome wasn't built in a day." And so it is with a team of international geneticists brought together recently by the National Psoriasis Foundation in the heart of that ancient city to discuss the progress of their work. The conclusion: years of research have passed and years lay ahead, but slowly and surely the genes behind psoriasis are being revealed.
Established in 1995, the International Psoriasis Genetics Consortium (IPGC) met in September to compare data and further refine their approach to unraveling the genetic secrets of psoriasis. The IPGC brings together the world's leading investigators in psoriasis genetics, including attendees from Sweden, Finland, Germany, the United Kingdom and the United States.
"The meeting closed on an upbeat note with the feeling that the next few years are going to lead to the identification of a large number of psoriasis susceptibility genes," said Anne Bowcock, Ph.D., of Washington University in St. Louis. Dr. Bowcock presented evidence that genetic regions on chromosome 17 are involved in psoriasis.
The consortium also recognized that individual genes are likely to have weak effects and that it will be important for the researchers to work together as a group to explore the interactions between the genes required for the disease to develop, Dr. Bowcock added. To date, researchers have identified 14 genetic regions that appear to contain genes involved in psoriasis.
DNA donated by Psoriasis Foundation members to the National Psoriasis Tissue Bank is being used by several of the researchers.
The Psoriasis Foundation is evaluating a proposal from the IPGC to assemble different samples of DNA to locate once and for all the exact location of a gene on chromosome 6, which is believed to make the major contribution to the inheritance of psoriasis. This year, the group established the strongest evidence yet that psoriasis is associated with chromosome 6 and their findings were published in the prestigious American Journal of Human Genetics.
The suspected genetic region holding the gene on chromosome 6 is located within the major histocompatibility complex (MHC). The MHC controls the body's ability to recognize foreign antigens (viruses or bacteria) and is essential to the immune system. About 180 functional genes are encoded in the DNA this region, and, 40 percent of those genes are involved in antigen recognition and other aspects of the immune system. Psoriasis may be triggered by an antigen produced by the body itself, rather than a foreign invader such as a virus, and the Foundation is funding research aimed at finding the antigen. The region on chromosome 6 associated with psoriasis is called PSORS1 for "psoriasis susceptibility 1."
The IPGC was established shortly after the discovery of the first location of a possible gene for psoriasis on chromosome 17. Yet inspiration for the IPGC dates back to 1989, when the Foundation invited U.S. and international scientists to Deer Valley, Utah, for a workshop focused on psoriasis.
Among the scientists' recommendations was the establishment of a large, centralized psoriasis tissue depository-a "bank" of blood samples from people in large families with psoriasis that researchers could use to conduct genetic studies. The Foundation and its members responded and formed the National Psoriasis Tissue Bank.
Approximately four years later, in 1994, the tissue bank opened its doors. Researchers were quick to use it as a resource. Using data from the bank, Dr. Bowcock and at that time her team at the University of Texas published an article in the prominent journal Science that announced the chromosome 17 discovery. The Foundation then acted on a recommendation from Dr. Bowcock to bring together researchers from around the world to collaborate and conduct large studies using the tissue bank's data. Hence, the IPGC was formed.
Previous meetings of the IPGC have been held in Stockholm, Sweden; Dallas; London; Cologne, Germany; and Nice, France, where some of the world's leading investigators in the field are located.
Chromosome 6 Evidence Grows
First posted Nov. 5, 2003
An international group of psoriasis genetics researchers funded by the National Psoriasis Foundation recently established the strongest evidence yet that psoriasis is associated with several genes, and their findings will be published in August in the prestigious journal Nature Genetics.
The results provide "unequivocal evidence," according to James T. Elder, M.D., Ph.D., of the University of Michigan, that psoriasis is associated with a genetic region located on chromosome 6 within the major histocompatibility complex (MHC).
The MHC controls the body’s ability to recognize foreign antigens (viruses or bacteria) and is essen- tial to the immune system. The MHC’s 3.6 million nucleotides, or basic elements of DNA, encode about 180 functional genes, 40 percent of which are involved in antigen recognition and other aspects of the immune system. Psoriasis is thought to be caused by a mixture of environmental and genetic triggers that cause inflammation deep in the skin and lead to the development of lesions. The genetic region associated with psoriasis is called PSORS1 for "psoriasis susceptibility 1."
Additionally, the research shows regions on chromosome 16 and 10 also appear to be associated with psoriasis. "The PSORS1 evidence is strong," Dr. Elder said, "but it can’t account for [all] genetic effects in psoriasis. PSORS1 seems to be most important for early onset of psoriasis."
In no fewer than five studies, significant evidence has been reported that a genetic variation in the PSORS1 location is associated with susceptibility to psoriasis. Yet, approximately 10 percent to 20 percent of people who do not have the disease carry the same genetic variation. Thus, researchers suspect other genes are involved. To date, researchers have reported 14 potential psoriasis susceptibility locations.
The group publishing the research, the International Psoriasis Genetics Consortium (IPGC), represents 10 labs and more than 20 researchers. The group meets yearly at an event sponsored by the Psoriasis Foundation to share progress in the search for genes. Additionally, individual researchers, such as Dr. Elder and Anne Bowcock, Ph.D., a researcher at Washington University in St. Louis whose research has associated psoriasis with a region on chromo some 17, receive individual funding from the Foundation to perform their research. |
