CH3ips off the old genetic block.

CH3ips off the old genetic block

Certain traits we inherit from ourfather, others from our mother. But the legacies of our parents linger on at the molecular level as well, in the form of genes that may act differently depending on which parent provided them--a phenomenon called genomic imprinting, which is related to why mammals persist in requiring parents of both sexes. In a search for the imprinting mechanism, two research groups in England and Canada have independently discovered chemical differences between paternal and maternal genes that they say could help explain the mysteries of imprinting, as well as why the course of a particular genetic disease depends on which parent provided the defective gene.

Scientists at the Institute of AnimalPhysiology and Genetics Research in Cambridge, and at the Ludwig Institute for Cancer Research in Montreal and Mount Sinai Hospital Research Institute in Toronto, discovered that DNA inherited from the mother apparently has more methyl groups (CH3) attached than does DNA inherited from the father. They found the telltale methyl groups after inserting easily identified foreign genes into the genetic material of mouse reproductive cells and following these so-called transgenes through several generations. The researchers measured the methylation of transgenes using standard tests for methyl groups. Although not all strains of mice tested showed sexual differences in the number of methyl groups on their DNA, some interesting patterns appeared.

Both research groups report in theJuly 16 NATURE that the methylation pattern is reversed when a child of the opposite sex of the parent has its own offspring. For example, a gene inherited from the father will be "undermethylated' in both his female and male offspring, but if the daughter has her own offspring, that same gene acquires more methyl groups during her egg development. The observations support the role of methylation in genomic imprinting, which by definition requires a mechanism that can switch gears depending on the parent's sex, says Carmen Sapienza of Montreal.

In addition, Wolf Reik of Cambridgesays that, because methylation has been implicated in regulating the expression of genes, the relative number of methyl groups may affect the outcome of a particular gene, such as the gene for Huntington's chorea. In that disease, if the defective gene is inherited from the father, symptoms begin during adolescence; if the mother is the one passing on the gene, symptoms do not begin until middle age--a difference that may be regulated by methyl groups on the gene, says Reik.