Epigenetics pops up again

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Epigenetics pops up again

Postby dignan » Mon Jul 24, 2006 4:26 pm

A study about frequency of parents transmitting MS to their children. They don't claim to understand why, but epigenetics is mentioned.



Men With Multiple Sclerosis Pass Disease to Offspring More Often Than Women in Families With Multiple Cases of Disease, Study Finds

July 24 (AScribe Newswire) -- According to a new study, men transmit multiple sclerosis (MS) to their children 2.2 times more often than women in families where the father or mother and a child have multiple sclerosis.

This study involved an investigation of 444 children of an MS-affected father or mother from 3,598 individuals in 206 families to compare the transmission of MS between affected men and women. The findings by researchers from Mayo Clinic, the University of California at San Francisco, the University of California at Berkeley and Kaiser Permanente will be published in the July 25 issue of the journal Neurology.

"Fathers with MS tend to have more children who develop MS than do mothers with the disease," says Brian Weinshenker, M.D., Mayo Clinic neurologist and study investigator. "When we looked at a large population of MS patients, when there was a parent and a child who had MS in a family, the child with MS got the disease twice as often from the father rather than the mother."

MS affects approximately 1 in 1,000 people, and it is twice as common in women as in men. In 85 percent of cases, no cause is known. For 15 percent of MS patients, a family member within a generation also is affected by the disease. For familial cases, no single gene has been identified that strongly predisposes a person to MS.

"Rather, a combination of genes and unknown environmental factors work together to cause multiple sclerosis," says Orhun Kantarci, M.D., Mayo Clinic neurologist and lead author of the paper.

The researchers theorize that men may have a greater "genetic load" of MS genes, which may explain their findings.

"The hypothesis of the study is that men are more resistant to MS, so they need stronger or a larger number of genes in order to develop MS, and then pass these genes to their children," says Dr. Kantarci.

He also explains that the overtransmission of MS by men in the study is not easily explained by hormonal differences between men and women or by genes on the sex chromosomes.

The findings shouldn't change how men with MS are counseled about the risk to their offspring, say the researchers. The risk of having MS if a person has an affected parent is increased by about 20-fold compared to not having an affected parent; the additional risk by virtue of having an affected father is not sufficient to change patient counseling practices, says Dr. Kantarci.

"The overtransmission by men is primarily of interest to scientists studying the mechanisms of genetic transmission of MS susceptibility," said Dr. Kantarci, "and may indicate that nontraditional, or so-called epigenetic factors, play some role in the transmission of MS."

The investigators also indicate that their findings should be confirmed in another study by other researchers to be widely accepted.

No intervention prevents men from passing on MS, say the researchers, who indicate the necessity for MS researchers to identify the reason for this overtransmission by men, including finding genes predisposing to the "parent-of-origin" effect observed in this study.

http://newswire.ascribe.org/cgi-bin/beh ... 6&public=0
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Postby BioDocFL » Tue Jul 25, 2006 8:09 am

Dignan,

Do fathers with MS have sons who get MS? That is the question that comes to me. I didn't see anything addressing that in the short article. The 2.2 to 1 ratio seems to coincide with the X chromosomes being passed down. So perhaps it points to the X chromosome. The father has only one X, which if that X is susceptible to MS, the daughter would get the susceptible X chromosome. If the mother has a susceptible X, then it is 50/50 that the son or daughter would get the susceptible X. If it is X related, the father would not be passing it down to his son. I need to get their original article and see if it addresses this father/son question. Interesting report though. Thanks for posting it.

Wesley
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Children?

Postby lyndacarol » Tue Jul 25, 2006 3:34 pm

I had wondered much the same as Wesley when I read the article. Wouldn't researchers have broken "children" down into "sons" and "daughters?"
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Postby dignan » Wed Jul 26, 2006 6:30 am

Here's the Pubmed posting of the same article.



Men transmit MS more often to their children vs women: the Carter effect.

* Kantarci OH,
* Barcellos LF,
* Atkinson EJ,
* Ramsay PP,
* Lincoln R,
* Achenbach SJ,
* De Andrade M,
* Hauser SL,
* Weinshenker BG.
Neurology. 2006 Jul 25;67(2):305-10.
Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. kantarci.orhun@mayo.edu

OBJECTIVE: Multiple sclerosis (MS) is approximately twice as common among women as men. If men have greater physiologic resistance to MS, they might theoretically require stronger genetic predisposition than women to overcome this resistance. In this circumstance, men would be expected to transmit the disease more often to their children, a phenomenon known as the Carter effect. The authors evaluated whether the Carter effect is present in MS.

METHODS: The authors studied 441 children (45 with definite MS) of an affected father or mother (197 families of interest) from 3598 individuals in 206 multiplex pedigrees. The authors compared transmission of MS from affected men with transmission from affected women.

RESULTS: Fathers with MS transmitted the disease to their children more often (transmitted: 18, not transmitted: 99) than mothers with MS (transmitted: 27, not transmitted: 296) (p = 0.032; OR: 1.99, 95% CI: 1.05, 3.77). Adjusting for both the sex of the affected child and multiple transmissions from a single affected parent, the sex of the affected parent remained as an independent risk factor for transmission of MS to children, fathers transmitting more often than mothers (p = 0.036; OR: 2.21, 95% CI: 1.05, 4.63).

CONCLUSIONS: The authors have demonstrated the Carter effect in multiple sclerosis (MS). These observations may be explained by greater genetic loading in men that leads to relative excess paternal vs maternal transmission. Linkage analysis in genetic studies of MS may be more informative if patrilineal transmission were given additional weighting.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
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Postby BioDocFL » Fri Jul 28, 2006 10:42 am

I couldn't get to the article above but I did find an earlier report about the parent-child relationship. Unfortunately for both of these I can only see the abstracts. Sure wish we could get better access to journals. I'm in research but still have trouble getting to full articles in order to read the details.

Our question was: Can a father with MS pass the susceptibility to a son, or only to daughters? The idea behind the question is: Is the susceptibility to MS X-linked? The abstract below shows, out of 22 fathers with MS, 21 had daughters with MS, and only 1 had a son with MS. To me that seems to support an X-linked scenario. We can't be sure but the one son may have received the susceptibility from his mother (don't know anything about her status though from just the abstract. I would like to get the authors' conclusions.).

Wesley

1: Ann Neurol. 1991 Mar;29(3):252-5. Links
Comment in:
Neuroepidemiology. 2002 Jul-Aug;21(4):207.
Parent-child concordance in multiple sclerosis.Sadovnick AD, Bulman D, Ebers GC.
Department of Medical Genetics, University Hospital, University of British Columbia, Vancouver, Canada.

It is now recognized that susceptibility to multiple sclerosis (MS) is determined in part by genetic factors. The gene loci influencing MS susceptibility are largely unidentified. In an attempt to better understand the mode of transmission, parent-child concordance for MS was studied in two large, population-based MS clinic populations. Among 75 parent-child pairs concordant for MS, we found 40 mother-daughter pairs, 13 mother-son pairs, 21 father-daughter pairs, and 1 father-son pair. Controlling for the known female preponderance in MS, the data show a paucity of father-son pairs. These data have implications for understanding the mechanisms of inheritance for MS susceptibility as well as for risk counseling in families of patients.

PMID: 2042941 [PubMed - indexed for MEDLINE]
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