PHILADELPHIA, PENNSYLVANIA - There is more variety in the DNA you might be thinking, deletions or additions of genetic material between individuals, called number variations (CNV), are a common source of genetic diversity. Now the preliminary work reported here today at the American Society of Human Genetics meeting suggests that men who have more than average CNV may be more likely to bulls children with eye cancer retinoblastoma. The research reflects the growing enthusiasm among geneticists for CNV, a type of genetic variation that has not received much attention until recently, but is now being linked to a number of diseases.
All young people who develop retinoblastoma in both eyes inherited a defective gene that caused the disease. But in 80% of cases, neither parent carries the mutation. Somehow, he was raised in the father's sperm. Nobody knows how it happens, but the researchers speculated that some fathers may be more sensitive to DNA damage than others. At the University of Pennsylvania (Penn U) and the Philadelphia Children's Hospital, the researchers spent about 7 years collecting cases of this rare cancer and to collect DNA from children and their parents. They are also inquiring about a range of environmental exposures that may have affected fathers, but this information is not yet available.
The genetic results, however, are slowly coming together. At the meeting, the geneticist Elizabeth Chao, a postdoctoral researcher at U Penn geneticist working with Arupa Ganguly, describes DNA taken from 169 fathers whose children have developed the disease. They identified 37 CNVs they saw as a big - more than 500,000 DNA bases - and in general found that more fathers had CNV as witnesses, about eight average against three. Twenty-one dads had undetectable CNV at all, but Chao suspect this may be due to the technology, which has difficulty picking up very small stretches of DNA that are duplicated or deleted.
Particularly interesting were CNV in genes that protect against DNA damage, such as breast cancer gene BRCA2 . Chao does not know if these CNVs are inherited by the parents of their own parents or if they accumulate with age. And it is too early to say how or even if CNVs contribute to the risk of retinoblastoma gene mutated. One possibility, Chao said, is that the high number of CNVs cause sort of DNA damage by making Dads less able to protect themselves against environmental aggressors such as radiation. Another explanation is that the CNV are merely "markers of a genome less stable," suggesting that these men are more vulnerable to DNA damage in general. The fathers are not at higher risk of cancer them -Same, Chao added.
Although these dads are healthy, the results are similar to other diseases related to high levels NVC. for example, take Li-Fraumeni syndrome, genetic disease that leads to a number of cancers. in a work published in August in the Proceedings of the national Academy of sciences and presented today, researchers at the Hospital for sick Children in Toronto , Canada, studied 11 affected families Li-Fraumeni syndrome and reported that those involved had an average of 12 CNVs in their genome, against three in controls. further work describes an increased burden of CNVs in schizophrenia , particularly in the DNA which is part of a gene.
Retinoblastoma is working "very preliminary," said geneticist Stephen Scherer of the Hospital for Sick Children, who participated in the study of Li-Fraumeni. In general, the CNV data is "getting a lot better," but the work is always difficult because different technologies provide different variations of the number of copies. "He's really, really hard" to both identify with CNV accuracy and determine their relevance to the disease, he said. Still, Scherer said, large rare CNVs identifications are likely to be accurate, and the approach offers new hope in the identification of DNA that is driving disease .
0 Komentar