Personal exomics
Individual DNA diagnostics has entered clinical practice
Ekaterina Shershunova, STRF.ru
Even experienced doctors sometimes cannot explain the cause of the disease and correctly diagnose it. In such cases, a new approach is needed, experts from the Center for Human Molecular Genetics in Wisconsin (USA) believe. Recently, they managed to establish the cause of an unknown intestinal disease by decoding the patient's DNA, Informnauka reports.A little boy named Nicholas Volker was suffering from an unknown serious illness.
At first, he just gained weight badly, and soon after he turned one year old, the disease turned into a severe stage: the boy began to have multiple abscesses in the intestines. They led to the penetration of bacteria from the intestine into the blood, and the child lived with constant sepsis. He was often given blood transfusions, injected with antibiotics, part of the intestine was removed, but a positive result could be achieved only for a short period of time. Later, the boy developed aplastic anemia, a disease in which blood cells cease to mature in the human bone marrow: leukocytes, erythrocytes, platelets. This is the most dangerous form of anemia, and it is fraught with severe infectious complications.
Scientists believed that the root cause of the disease could be disorders in the immune system, but it was unknown what exactly was working wrong and how to deal with it. Geneticist Elizabeth Warsi and her colleagues performed exome sequencing and found out which gene was working incorrectly in the patient. This information allowed the boy to be cured. An article about the study (Elizabeth Worthey et al., Making a definitive diagnosis: Successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease) will be published in the journal Genetics in Medicine, and its preprint is already available on the publication's website.
The complete decoding of the human genome is still a very expensive and time-consuming procedure. In this case, not all nucleotide sequences were deciphered, but only exons – sections of DNA that encode sequences of amino acids in proteins. This method has only recently entered clinical practice, but already demonstrates brilliant results. The absolute majority of genetic diseases are associated with a violation of the structure of proteins. The method of exomic analysis allows relatively inexpensive and quick to obtain information about which proteins in the patient are working incorrectly.
The researchers analyzed 16,124 genetic sequences. They were compared with the genetic sequences characteristic of healthy people. Scientists were able to detect a mutation in the XIAP gene in the patient. His variant of the gene differed from the 2000 control sequences obtained from volunteers, and was not found in any other living organism up to drosophila. The protein, which is encoded by the XIAP gene, works in immune cells and plays a key role in activating the anti-inflammatory immune response. It is also necessary to trigger apoptosis (programmed cell death). When the researchers checked the structure of the XIAP gene in the boy's mother, it turned out that the mutation was inherited from her. The XIAP gene is located on the X chromosome, and therefore such a mutation is not dangerous for women. The disturbed protein is balanced by the normal one encoded on the second X chromosome. But for a boy with only one copy of the gene, the mutation would be deadly if not for timely diagnosis of the disease.
Based on the results of the study, doctors decided to transplant bone marrow – replacing their own hematopoietic cells with a mutation in the XIAP gene with donor cells with a normal copy of the gene. After the treatment, the boy began to feel much better. The researchers note that forty–two days after the bone marrow transplant, the child began to eat ordinary solid food for the first time in his life - the intestines gained the ability to digest it.
Geneticists hope that such an example will be the beginning for the widespread use of exomic sequencing in cases of diagnosis and treatment of rare diseases.
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13.01.2011