Knowing your genome can help you get the jump on diseases for which you are at risk.  A man in Britain with BRCA2 opted for prostatectomy even though he had no symptoms.
http://www.bionews.org.uk/page_303865.asp   The BioNews article contains a number of links to additional articles on this topic, one of which reports the man’s removed prostate was discovered to be cancerous after all.

Do you think you would opt for preventive surgery if you discover a genetic predisposition for serious illness?

What factors would you consider?

I’m a real sucker for animal videos on YouTube and came across this edited version of an earlier post which I had enjoyed a lot. The new one added a very lovely musical background and several captions. (Cllick “Read More” if the video isn’t visible yet.)

I have to ask about one caption, though, “What is ‘God doesn’t make mistakes’ supposed to mean?” It’s one thing when a little girl says “God didn’t make a mistake when he made me” (the source of the caption). Her parents gave her a way of forestalling those who would look down on her or who would criticize their choice to cherish her.

I understand it is used to celebrate the value of lives affected by genetic anomalies. But, please!! I dare to object because (1) it implies that God directs the creation of every individual life (otherwise the results could hardly be considered by anyone as a mistake made by God) and (2) to be consistent, the same would have to apply to all children born, regardless of degree of malformation. If you have ever been to a human genetics conference and perused the poster session (thousands of posters), you will appreciate that Down Syndrome is relatively speaking, a very mild condition. The quality of life is marvelous in comparison with many infants who survive far more devastating genetic defects (one definition of “defect” being “mistake,” I suppose). In such cases, it is a whole lot harder to buy the idea that there were no errors (mistakes) involved in that individual’s development. Seeing the more extreme cases helps one appreciate that at what point some might decide to terminate is indeed relative and a difficult personal decision. The infants that survive many genetic problems are exceptions in that in the majority of similar cases, “nature (God?) takes its course” and spontaneous, natural abortions occur. Perhaps in recognition that a mistake had occurred?

Yes, the bond between the child and his dog is incredible and very touching. It enriches life to focus on the emotional wealth that humans (and animals) can have that makes life worth living in the face of intellectual challenges and unusual appearances. That certainly does not mean that each embryo is the result of some divine plan (Is it God that prompts people to have sex on any particular occasion?). To suggest that diminished the video for me, needlessly and pointlessly.

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Your baby has just been diagnosed with a genetic disorder.  Before you can really grasp that, the doctor recommends that you and your partner have genetic tests to find out whether you are carriers. In other words, whether this disorder came from you. Which one of you? Either one? Both?  It’s bad enough to find out your child is sick, will have life-long problems, or maybe even a really short life. Now you find out she got it from you. Nice. Really nice. ‘Course you’re also wondering about your other child. It’s going to be weeks before the results come in. You look at them. They look the same. Beautiful. But now, oh God, what now?

You always wanted three. But it all seems fraught now; how did family get so complicated?

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Sure, sometimes pregnancies end badly. But you tried hard to do everything right. You both did. And they “had all their fingers and toes.” Then you wonder, how does it ever manage to turn out right? Friends without a care in the world—the worst thing their kids ever have had is a skinned knee!

You didn’t aim all that high, were happy just to have a little life. But now it seems like, well, that life is gone. You’ve been forced off the path, that wonderful, plain, and simple path of sunrise, sunset, with your kids carrying on after you’re gone. And their kids after that.

©WongSzeYuen/ Shutterstock

Most breast cancer is not hereditary.  Available estimates say that genetic susceptibility (among white women) is involved in 5 to 10% of breast malignancies and 10 to 15% of ovarian cancers (BRCA mutations can cause either).

We all possess wonderful genes called tumor suppressors. Two of the genes known to suppress breast and ovarian cancer tumors are called BRCA1 and BRCA2.  BRCA (pronounced brack’ uh) stands for BReast CAncer.  Normally, we have two healthy copies of each tumor suppressor gene.  When a mutation, or change, occurs causing one gene to work incorrectly, the cell can still continue to suppress abnormal growth UNTIL something breaks the second gene as well. When both genes of a pair are damaged, the gene can no longer work its tumor suppressing magic and cancer can result. So when one inherits a BRCA gene with a harmful mutation, it means there is just one gene, instead of a pair, standing guard, resisting tumor-generating forces.  One’s risk of breast cancer is then higher than that of the general population.  It could be as much as five times higher, 60% instead of 12%, although this might be an overestimate. (Source: http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA#a2)

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It is important to appreciate that not all children of an adult with a BRCA1 or BRCA2 mutation will inherit the damaged gene instead of the healthy one. Genetic counselors can help various family members estimate the risk they face.  Naturally, those who have experienced the disease, or survivors who knew relatives who were killed by it, feel great concern for relatives that may face increased risk.  However, knowledge of risk is something not everyone desires. Perception of the burden of having breast or ovarian cancer varies also.

©Juriah Mosin/Shutterstock

But what about minor children?  For many years, most genetics professionals have counseled against genetic testing of children to determine either carrier status or genetic susceptibility.  Personally, I am convinced that it is not the test or test results themselves that can be harmful to children. Rather, it is the meaning given those results by the adults with influence over the children.  Even mature teenagers are vulnerable to being overwhelmed by their parents’ interpretation of test results.  Parents and others must have the fortitude to override their worry and concern in order to respect family member’s autonomy and right to make their own decisions in the wake of genetic knowledge, regardless of their age or attitude.

© 2011, 2012 Jane Belland Karwoski                                        http://twitter.com/mybluegenome

Read more about this in BioNews newsletter, April 16, 2012:

http://www.bionews.org.uk/page_138787.asp

©Bryan Sikora/Shutterstock

It shouldn’t be about blame, of course, in the first place. But, what is incomplete about the diagram below?

When a child is diagnosed with an X-linked recessive disorder, the inheritance pattern is often illustrated with a diagram like this one. Notice where the buck stops.

What parents might be shown

What could going back one more previous generation reveal? There are (at least) five possibilities.

First, let’s be clear, the mother might not be a carrier to begin with.

There might not have been a genetic alteration previous to the diagnosed child; the mutation (to use the “m-word”) just sprang up suddenly in the early embryotic divisions of the affected fetus, causing the disorder. In that case, the mother is not a carrier. However, this diagram might be used to explain how things usually work, even when the mother has not been  identified as a carrier through genetic testing.

A second possibility: the mother does have the mutation, but only in some of her ova, or egg cells. She, also, would not be identified as a carrier because the mutation does not affect the DNA in her entire body. A blood test would not reveal the mosaicism (that means some egg cells are affected, others are not) because the DNA in the rest of her body, and many of her ova, does not code for the disorder.

Further possibilities occur when the mother is identified by genetic testing as a carrier in the usual sense (each pregnancy having 25% chance of an affected son, 25% chance of a carrier daughter, 50% chance of an unaffected child, as illustrated in the diagram). But how does she happen to be a carrier?

That brings us to the third possibility: A “spontaneous mutation” occurred making the mother a carrier without previous genetic history in the family. It is often estimated that in some X-linked recessive disorders, around 30% of affected pregnancies result from such “out of the blue” genetic changes.

©Voronin76/Shutterstock

Fourth possibility: She was a carrier daughter of a carrier mother. The damaged gene “runs in the family,” although there may never have been an affected son born to anyone before this. Of course, everything said above about the mother, can also be applied in the grandmother’s case.

Fifth possibility: Because a daughter gets an X chromosome from each parent, the mother could have inherited the mutation from her father! Gosh, that’s something you seldom hear!

©Lisa F. Young/Shutterstock

But yes, in spermatogenesis, mutations occur. If the sperm carrying an X chromosome with an altered gene fertilizes the egg, well, there you have it, a new carrier daughter. No one will suspect, there will be no reason to test, until an affected grandchild of the new carrier’s father is born and begins to manifest symptoms of a disorder that no one knew ran in the family…because it didn’t.

I’m not sure why knowledge of these different scenarios should affect the burden of guilt felt by many mothers who are implicated in genetic inheritance patterns, but I strongly suspect that it does. After all, guilt is an emotion and therefore irrational to begin with. It is easy to say, “It’s nobody’s fault.” But in the case of X-linked recessive disorders, given the way the inheritance has been diagrammed for generations, is it any wonder so many moms feel it all came from them?

When a disorder “runs in the family,” it might be a source of stigma. Whether it is or not, all depends.

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Being stigmatized, or marked as different and undesirable, involves the loss of social standing. One is marked as being less than others and is aware of being so marked.

© Ioannis Pantzi

Usually, there are negative stereotypes associated with stigmatized groups. The classic  work on the subject is Stigma: Notes on the Management of Spoiled Identity (1963), by  Erving Goffman, in which stigma is described as tainting and discrediting. Stigma is  defined by a social environment because it results from the way others see us. To the  degree that we “buy into” their judgments, shame is also attached to conditions that are  stigmatized.

The opposite of stigma can be the healthy pride that comes from feeling respected by others. Whether others respect us can depend upon how well we are fulfilling our social roles as defined by our surrounding culture. Health and beauty are generally respected and admired. In reproductive matters, producing offspring, especially males, is a source of pride of accomplishment for men and women in many societies. For any particular culture, the more social standing that results from producing children, the more likely it will be that having no children, or imperfect children, will result in social stigma.

© cofkocof

We can regulate stigmatization by controlling our immediate social environment. The people we associate with, the viewpoints we read or listen to, and the information we divulge can all affect the number of negative evaluations coming at us.

For more information on stigma & health:  http://www.stigmaconference.nih.gov/papers.html

© 2011  Jane Belland Karwoski

I’d like you to meet my blue-jean–clad gnome.

Thank you, my friends, K.T. and Cat!

© Greg Epperson

That’s how a one might feel if she or he is concerned about genetic risk but conscientiously objects to reproductive technology (reprotech). And if one’s risk is not X-linked (see preceding blog entry), then even natural sex-selection isn’t going to help as boys and girls will be at equal risk of inheriting the disorder involved.

Here is where one must take a good, long look at “risk.” Just what does risk involve? What does it mean to you as an individual?

The same risk factor (a numerical estimate that your genetic counselor computes from many pieces of information) can be viewed as minor or overwhelming.

Your risk perception depends on a number of things:

Do you have experience with or personal knowledge about the condition?

© Jaren Jai Wicklund

Your own experience will affect how you perceive the severity of the condition which, in turn, will affect how daunting a particular risk estimate seems to be. Where there have been adequate supports to help the affected person and their family live an enjoyable life, the impact was likely less than for a family who did not have, for example, a social network to call upon for help, supportive teachers and school system, or financial assistance with medical expenses and caregiving if needed.

In thinking of the possibility of having a child with the genetic disorder, consider whether treatment for it is available. Bear in mind that not all medical professionals know everything there is to know about genetics, the condition, or prospects for treatment now or in the future, so you will need to be proactive and educate yourself. Care management can also vary widely. Better care can improve quality of life and lengthen life, so advocating for your child, should he or she be affected, will become a part of your life.

© Laurin Rinder

Quality of life is a very slippery concept. The same situation might seem to provide fine quality of life to one person or family, but seem to be a miserable way to live to others. Interestingly, people with a disability usually rate their quality of life as higher than onlookers do (see The Disability Paradox: High Quality of Life Against All Odds. Social Science & Medicine, Volume 48, Issue 8, Pages 977-988. G.Albrecht).

In addition to how severe the condition seems to be to you, it is important to consider how you view personal responsibility. In some communities and families, babies being born less than ‘perfect’ is simply a fact of life, something that could and does happen to anyone–an occasional side effect of the natural process of procreation which is everyone’s right. In other communities or families, human control over the environment has become so commonplace that it is assumed we can and should control just about everything. Even if you disagree with the prevailing viewpoint, it will likely be in the back of your mind. So it is a good idea to acknowledge the ideas you’ve been brought up with and decide what your own convictions are. You are the ones who will be living day-to-day with your decision to have (or not have) a child or children. If you do decide that having a family outweighs what you perceive the risk of passing on a hereditary condition to be and you do begin a family, it is wise to surround yourself with supporters of that decision. A positive attitude will be important for you, but even more so for any child born affected by the condition.

What are the options for carriers who want children, but without resorting to selective termination or destruction of embryos that will not be implanted? This is one situation where carrying an X-linked trait has an advantage over carrying an autosomal trait. (Genes coding for autosomal traits are located on chromosomes other than the sex chromosomes that determine the sex of the embryo.)  Carrying an autosomal trait has the advantage of signifying little unless one’s partner also carries it. That situation does occur, of course, and will be discussed in a subsequent blog entry.

© waterlilly

The primary option for carriers of X-linked traits is to do all one can to encourage conception of females. Because a female has two X chromosomes, the influence of the “good” X can outweigh the influence of the X with the harmful gene. Daughters would have a 50/50 chance of being carriers themselves, but it is very unlikely they would have the disorder’s symptoms unless there was something wrong with the “good” X chromosome. Please note, this is an oversimplification, as some female carriers do show some symptoms of the disorder they carry, even with one “good” X. In fact, any time genetic information seems straightforward, Beware! It is probably an oversimplification. In genetics, more detailed information often does not lead to greater clarity, but rather tends to reveal the situation as “curiouser and curiouser”!

Is it possible to choose the sex of your baby?

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There is quite a history to approaches aimed at getting a boy or, in this case, a girl. Leaving aside folk wisdom over the ages, a Dr. Shettles promoted a method based on the vaginal environment and the timing of intercourse in relation to ovulation. Those ideas were based on differences between X- and Y-bearing sperm. His book, How to Choose the Sex of Your Baby, was revised in 2006. Following his instructions might increase the odds of having a baby of the desired sex.

The success rates of conceiving the sex you want vary widely, depending on whom you ask. When you research this yourself, don’t just put confidence in someone’s report that “a study found such-and-such” supporting the conclusion they are promoting.

© Andriianov

Be sure to ask which study? Do they list the reference (journal, volume, issue, pages)? Is the journal available or is it impossible to find? Ask your reference librarian to help if you are not used to doing searches. The article’s authors may not have come to the conclusions the reporters thought they did. Or, the evidence presented may support other conclusions, as well, or be open to interpretation.

A technology called MicroSort® separates X-bearing from Y-bearing sperm. The desired kind can then be inserted into the uterus (intrauterine insemination, or IUI). The first report of healthy daughters born to avoid an X-linked trait using MicroSort appeared in Human Reproduction, 13(9), 2367-2370, 1998, by Fugger, Black, Keyvanfar, and Schulman. More recently, a Microsort® clinical trial update was reported online in 2008 by DS Karabinus in Theriogenology, 71(1), 74-79. That journal title, in case you were wondering, means animal (including human) reproduction.

© Flashon Studio

According to www.microsort.net/results.php , after sorting for X-bearing sperm, 88% in a specimen are indeed X-bearing, but 93% of babies conceived were female. Keep reading, however, because conceptions resulted from 16.6% of IUI attempts. With IVF or ICSI (intracytoplasmic sperm injection), the pregnancy rate increased to 34.7%. These results were last updated three years ago. See http://www.fertility-docs.com/glossary.phtml for definition of terms and procedures.

Another approach to sex selection is based upon the mineral balance in the mother’s diet which I will explain in the next blog entry. Yes, there are ways to increase the chances of having a daughter. By how much depends on whom you ask and how many methods are used in combination.  When preimplantation genetic diagnosis is unacceptable, doing what one can to conceive a female can be an improvement over either avoiding conception entirely or accepting the one in four chance in each pregnancy of an X-linked disorder affecting the resulting child.