(© Bonnie Schiedel. Originally published in Canadian Health, March/April 2008). 


Science offers hope for those at risk for gene-based diseases, but it also raises ethical dilemmas

New lung cancer genes discovered. Stepped-up genetic testing sparks debate. Headlines like these are a clear sign of the enormous amount of genetic research underway. To get a handle on what this research may mean to you, you need to understand the basics of genetics. Read on for your crash course. 

A Genetics Primer
DNA Deoxyribonucleic acid. Found in every cell in your body except mature red blood cells, this molecule carries genetic information. Tightly coiled, it resembles a twisted ladder, known as the double helix. Each rung on the ladder consists of pairs of chemical bases symbolized by the letters A (adenine), T (thymine), G (guanine) and C (cytosine). Think of DNA as your body’s architectural blueprint.

RNA Ribonucleic acid. This worker molecule follows DNA’s directions to make the proteins that perform your body’s chemical reactions and form the structure of all its cells. 

GENE A piece of a DNA molecule that acts as a how-to manual for RNA. Each gene has a DNA code, a sequence of individual building blocks formed by different combinations of base pairs — for example, AT, TC, CG,GA — which spell out exactly how to make a particular protein and, ultimately, a particular person with his or her own unique traits. Genes determine characteristics from eye colour and height to susceptibility to major diseases and the way the body processes medicines. We each have an estimated 25,000 to 30,000 genes. 

GENOME This refers to all the DNA in one set of chromosomes. The Human Genome Project (HGP) was a huge 13-year international effort, completed in 2003, which identified and mapped the sequence of human genes. 

CHROMOSOME A strand of DNA containing hundreds or thousands of genes. You have 46 chromosomes: 23 from your mother and 23 from your father. A woman’s egg contains only an X chromosome, while a man’s sperm can contain either an X or a Y. If an X sperm fertilizes the X egg, the resulting baby is female (XX). If a Y sperm fertilizes the X egg, the baby is male (XY). 

Alleles
Each alternate copy of agene is called an allele (from the Greek for of one another). The location of these alleles on your chromosomes is what determines that you are five foot six inches tall, while your brother is a foot taller, whether most of the people in your family have brown curly hair while yours is blonde and straight, or whether you can curl up the edges of your tongue, just like your mom can. The random mixing and recombination of parental chromosomes that occurs during conception is the reason siblings can sometimes look very different from one another. 

Of the 23 chromosomes you inherit from each parent, only one is a sex chromosome (an X or a Y). The other 22 are non-sex chromosomes, called autosomes, which are classified as dominant or recessive (see “ Genetic Disease,” below). 

Genetic Diseases
Genetic conditions occur when there is a change, known as a mutation, in one or more genes. These mutations could have happened long ago and been passed down through a family for many generations. Or, they could be more recent —the result of exposure to radiation or chemicals. Sometimes mutations occur spontaneously and randomly. There are three major forms of genetic conditions and diseases.

1.Chromosomal conditions In chromosomal disorders, the problem is linked to the genes in a whole chromosome or segment of a chromosome. Down syndrome (extra genetic material on chromosome 21) is a chromosomal condition. 

2. Single- gene conditions (monogenic or Mendelian) Single-gene diseases are caused by a mutation in one gene and are passed on in three main ways. 

Autosomal dominant disorders A child needs to inherit only one flawed gene or series of genes from a parent to develop the disease. Generally, each child of a parent with the mutated gene has a 50% chance of developing the disease. An example is Marfan’s syndrome, which affects connective tissues such as tendons and ligaments. 

Autosomal recessive disorders To be at risk, a child needs to inherit a defective recessive gene from both parents, who themselves may have the disease or may just be carriers of the gene. Each child has only a 25% chance of developing this type of disease since the child could inherit one of four possible gene combinations: a normal allele from both parents, a normal gene from dad and a mutated one from mom or vice versa (making the child a carrier who may eventually pass the condition on to his own child), or a flawed gene from both. The lung disease cystic fibrosis is autosomal recessive.

X-linked disorder A child inherits a single abnormal gene located on one of the X chromosomes from either parent. Males are generally more vulnerable since they lack a second X chromosome with a potentially good copy of the gene to compensate. Hemophilia is an X-linked disorder.

3. Multifactorial (polygenic or complex) condition Multifactorial diseases, such as Alzheimer’s disease, are triggered by a mix of multiple gene mutations and environmental and lifestyle factors. 

Genetic Counselling
Counselling is often recommended for prospective parents who have reason to believe their offspring will be at an increased risk for a specific disease — for example, if one or both of the parents is from a particularly susceptible ethnic group or the couple already has a child with a genetic disease. People who have several blood relatives diagnosed with an adult-onset genetic condition, such as certain kinds of breast and colon cancers, may also seek counselling. 

Bethany LaFlamme (some details have been changed to protect her privacy) a 29-year-old from Thunder Bay, Ont, falls into the latter group. A few years ago, her dad was diagnosed with oculopharyngeal muscular dystrophy (OPMD), an autosomal dominant or recessive disease that leads to vision and swallowing difficulties. Particularly common in Quebecois families, OMPD is linked to a gene defect on chromosome 14, and most often develops in person’s 40s or 50s. Bethany’s dad wasn’t too surprised — his mother and half of his 12 siblings have OMPD. “As soon as my dad was diagnosed, I set up an appointment for genetic counseling,” says Bethany. 

Before you undergo genetic testing for a particular condition, you first have to have genetic counselling, which takes about an hour, according to Carol Chemin, a genetic counsellor at the BC Cancer Agency in Vancouver. The counsellor asks the person to gather as much family medical history as possible beforehand in order to create a three-generation family tree. “We help the person decide whether to proceed with the test or not. For example, it may show that you have an increased risk of a disease, but not necessarily your actual chances of getting it.” 

After testing, the counsellor helps you interpret the results and, if you test positive, understand what the practical implications are, such as whether other blood relatives need to consider testing, what lifestyle changes you could make to possibly reduce your risk of developing the disease, or how to cope with a condition that you will certainly develop, such as OPMD. A counsellor can also help answer questions about ethical and legal concerns. Genetic counselling at a public health-care facility is free. 

After counselling, LaFlamme had a simple blood test at her local health clinic. Fortunately, she does not carry the OMPD gene mutation and will not develop the disease. “It was liberating feeling, knowing I didn’t have to worry about it anymore,” she says. 

Many questions
As we understand more and more about genetics, we must also struggle with more legal, moral and ethical questions for both real and potential scenarios. 

Many clients ask if they will be denied life insurance if they carry a particular gene or genes, says Chemin. “We tell patients that we really don’t know what kind of impact, if any, genetic tests will have on life insurance. When you apply for life insurance, you have to give information about your family medical history whether you’ve had genetic testing or not.” Currently, Canadian insurance companies cannot ask for a genetic test. 

Can you go to a fertility clinic and ask to have in-vitro fertilization (IVF), then select an embryo that will develop into a female with her mom’s blue eyes and her dad’s height? Nope. But should you be able to? Some private American clinics let you choose whether to have a male or female embryo via new sperm-sorting techniques. 

And there are exceptions in Canada. Before Charlottetown, P.E.I. residents Cynthia and Joe Bacher (not their real names) got married, they knew that Joe was a carrier of a mutation on the BRCA2 gene, which would mean that any female children would have a nearly 50-50 chance of developing breast cancer, and all children would be at higher risk for other cancers, including ovarian and pancreatic, or being carriers themselves. Since Joe’s mother and maternal grandmother died in their 30s of breast cancer, the Bachers wanted to be sure that they did not pass along the autosomal dominant mutation. They opted for a procedure called pre-implantation genetic diagnosis (PGD), which identifies embryos that carry a flawed gene or genes. 

Only embryos that are free of a suspect gene are implanted in the mother’s womb for gestation. Some considered their decision controversial, says Cynthia, because PGD is generally done only in cases where developing a disease is certain, such as in Huntington’s Disease, a degenerative and fatal neurological condition. “It was a painstaking, heart-breaking, expensive process, but it was very important to us to pull this mutation from our family tree,” says Cynthia, 35. After seven years and two unsuccessful IVF cycles, including one after which PGD found that all the embryos had the mutation, the couple is now happily expecting healthy twin girls. 

The burden of knowing
Is it a good idea to live with the terrible knowledge you could potentially develop a serious disease? On the other hand, if you know you have a higher-than-usual risk for colon cancer, you can have earlier, more rigorous screening and make lifestyle changes to help reduce the likelihood of getting it.

In the future, when genetic testing will likely become commonplace, other problems will arise. Should, say, a firefighter applicant be turned down because his genome, combined with workplace exposure to smoke and chemicals, means his cancer risk is too high? Would you marry someone with the gene for early-onset Alzheimer’s disease? In the years to come, medical and legal policymakers—and the rest of us—will face some challenging decisions. The more knowledge we acquire of our genetic makeup, the more responsibility we bear. 

For more on genetics, see Genetics for Dummies (Wiley Publishing, 2005), by Dr. Tara Rodden Robbinson. Or go to:

www.humgen.umontreal.ca A huge database on Canadian legal, ethical and social issues related to human genetics

http://cagc-accg.ca The website for the Canadian Association of Genetic Counsellors, including a list of Canadian genetic clinics

www.lhsc.on.ca/programs/medgenet The website for the Canadian Directory of Genetic Support Groups

www.genome.gov The U.S.-based website for the Human Genome Project, including information on the latest and up-and-coming research