Schizophrenia Daily News Blog

Schizophrenia Genetics, Imprinting

The Wall Street Journal columnist Sharon Begley had a good article this week on how imprinted genes seem to be the key to some diseases (including, potentially, schizophrenia), and offer paths to possible cures.

Begley notes, in the article

"that whether a child's traits are shaped by mom's genes or dad's genes isn't a simple matter of recessiveness or dominance, let alone of pure luck, as the textbook wisdom says. Instead, some genes come with molecular tags saying (in biochemical-ese), "I come from mom; ignore me," or "You got me from dad; pretend I'm not here."

Such genes are called imprinted. Unlike recessive or dominant genes (such as for black or blond hair), which are composed of different molecules, these genes are identical except for the silencer tag sitting atop them."

The result is that if the active gene is defective, there is no working backup; a healthy but silenced gene from the other parent can't step into the breach. In the joke, mom's beauty genes and dad's brainy genes were silenced, leaving mom's dimwitted genes and dad's homely ones to call the shots. This concept of imprinted genes is becoming a popular topic to research. Begley states that imprinting may be responsible for the inheritance of "...conditions such as autism, diabetes, Alzheimer's disease, male sexual orientation, obesity and schizophrenia from only one side of the family."

Begley describes "the vast majority of imprinting" as occurring automatically (prior to birth). However, she notes "in some cases it can result from outside interference." She says that interference such as toxic chemicals "may eliminate the silencer tag," and thus cause negative effects, which have the potential of being passed on to future generations. An example of research that investigates this idea is the study of lead exposure in pregnancy and its link to higher incidence of schizophrenia.

More examples of the biological research and discoveries stemming from this topic (as described by Begley), include:

"A gene on chromosome 9," is linked to autism. Further, it seems to have an effect only if it comes from the father. Also, there are single genes on chromosome 2 and 22 which are linked schizophrenia. Again, "only the copies from (the father) count." Thus, it appears that, "...having a family tree mostly free of these diseases is therefore no assurance of good health. If the disease runs on dad's side, his gene may be defective, and that is the one that matters."

As researchers discover "more imprinted genes," they are beginning to notice "that the silencing tag can be knocked off." However, this "knocking off" seems to have negative consequences. To better understand this, consider a recent animal study:

When fetal rats were exposed to two toxic chemicals -- a fungicide called vinclozolin commonly used in vineyards and a pesticide called methoxychlor -- they grew up to have slower- and fewer-than-normal sperm, Michael Skinner of Washington State University and colleagues report in the journal Science. The abnormalities were inherited by the rats' sons, grandsons and great-grandsons.

Professor Skinner stated, "(t)hat environmental toxins can induce a transgenerational genetic change is a phenomenon we never knew existed." When considering how it occurred. Skinner, further stated that the transgenerational genetic change was probably not the result of harmful mutations because they "become rarer with each generation." However, he did say that imprinting changes, 50 of which have been detected by his research group, "persist through the generations."

Source: Wall Street Journal, June 24, 2005.

For more information on Genomic Imprinting see:

GENOMIC IMPRINTING : A TALK WITH DAVID HAIG

Genetics of Childhood Disorders (Yale University)