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11 years ago
Does this headline make sense?   Study: Autism linked to genetic mutations, mother's age"Almost all cases [of spontaneous mutations] happen in the mother and are transmitted by the mother," he said, adding that the trait for Down is transmitted at the moment of conception. The trait is not hereditary in the same sense a "disease gene" is transmitted from one generation to the next.  `Michael Wigler

Malaspina-
"The causal mechanism underlying the well-established relation between advancing paternal age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males age. Point mutations are well known to increase with advancing paternal age while other errors such as altered copy number in repeat DNA and chromosome breakage have in some cases also been associated with advancing paternal age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between paternal age."
Other names for spontaneous mutations  are de novo or non-familial mutations or germ line mutations. Spontaneous mutations could be a misleading term.
In some syndrome associated with the paternal age effect the testis actually selected for the sperm with the mutation.
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=12900791&dopt=MEDLINE
Perrin MC, Brown AS, Malaspina D.
2Department of Psychiatry, School of Medicine, New York University, New York, NY.

The causal mechanism underlying the well-established relation between advancing paternal age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males age. Point mutations are well known to increase with advancing paternal age while other errors such as altered copy number in repeat DNA and chromosome breakage have in some cases also been associated with advancing paternal age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between paternal age and schizophrenia. Evidence suggests that advancing age as well as environmental exposures alter epigenetic regulation. Errors in epigenetic processes, such as parental imprinting can have serious effects on the offspring both pre- and postnatally and into adulthood. ........
In biology, if you research spontaneous mutations you will see that in plants, animals and human spontaneous mutations occur with a far greater frequency in the paternal germ line.

http://www.pnas.org/cgi/content/full/94/16/8380


EvolutionMale-biased transmission of deleterious mutations to the progeny in Arabidopsis thaliana Carrie-Ann Whittle* and Mark O. Johnston
Department of Biology, Dalhousie University, 1355 Oxford Street, Halifax, NS, Canada B3H 4J1
Edited by Ronald R. Sederoff, North Carolina State University, Raleigh, NC, and approved February 3, 2003 (received for review January 29, 2003
THE AGE OF THE FATHER AND THE
HEALTH OF FUTURE GENERATIONS?
Leslie B. Raschka M.D., Associate Professor (retired),
Department of Psychiatry, University of Toronto
Address: 27 Edgecombe ave, Toronto, Ontario, Canada
M5N 2Xl, Tel. (416) 783-6938
2
Abstract
Purpose: To assess the role of paternal age in the origin of genetic illness in future generations.
Data Sources: All reference data originated in English language international scientific literature and findings of original research conducted by myself.
Study Selection: Original articles published between 1938 and 1998 were selected according to the stated purpose. One article was written by myself.
Data Extraction: The present paper deals with 4 subtopics: andrology, genetics, pathology, and psychiatry.
Results: Nine articles reporting on 1399 patients described the deterioration of the quality of semen related to ageing. Five articles reported an increased mutation rate in the male germ cells as compared to the female...
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wrote...
11 years ago
Spontaneous means they simply happen, with no known cause. As to the question of the mother's age, or the paternal age, yes, of course, there is more opportunity for spontaneous mutations (these have nothing to do with germs but deal with microbal levels) simply because the person has lived longer and thus had more opportunity for mutation, but it is not necessarily a factor of age. Does that make sense? It's a pretty fine point, but an important one.
The other side of the picture is that a mutation is a mutation - something that differs from the norm. It is just as possible to have a positive mutation (for example, to give birth to a child who is at high genius level) as to have a negative mutation.
There are also schools of thought -- and they are pretty impressive -- that state mutations have nothing to do with the age of either parent, but rather with the effects of pollution upon the body. There are more mutations per thousand(alzheimers, down syndrome, etc) in densely populated  areas than there are in third world countries. So there may be something to that theory. The third world citizens don't breath in gasoline fumes, aren't subject to all the chemicals that the more populous countries use, eat simpler diets, aren't obese - there is a long list of differences, any or all of which could contribute to the differences in mutational rates.
wrote...
11 years ago
Yes, the headline makes sense.  It is important to understand why it makes sense and also to understand that it is only an association, not an accusation.  Increasing age is associated with increasing risk of mutations because all of the eggs that are in the ovaries were produced years earlier.  So, since mutations accumulate over time in various cells, the fact is that an older mother will have more mutations in the egg cells that a younger mother.  It may be because the mutations are not repaired as well as in younger mothers or due to other factors, but it is well-established that increasing maternal age (especially over 40) is strongly associated with certain disorders, such as Down syndrome.  It is less clear that paternal age matters.  This is due to the fact that there are lots of sperm germ cells producing lots of sperm.  So, the chance of getting a mutation from the father is less.  In the mother, there is (usually) only one egg available for fertilization after ovulation.  So, if a mutation has occurred in the egg, it will be carried to fertilization (if the mutation is not lethal to the egg).  A mutation in the sperm may actually decrease its chance of being the fertilizing sperm.  For instance, if trisomy 21 occurs, then that sperm cell is carrying extra DNA, which may make it slower and decrease its chance of getting to the egg for fertilization.
wrote...
11 years ago
yes this is positive. As studies have shown the andopopoly gene dipicts the exact carbonation of germs ( or germompopoli) so, in conclusion the dysregulation of epiggenetic aplogations, polates the eckogenesis aergo,

ITS DA M0MS FALT

becaZ SH3 2 0ld
wrote...
11 years ago
I think its true because nearly every mother with autistic infants is at least 35 years old.
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