geneIQ – Genetics and Diagnostics

Why do we need to find mutations in human genes? 

A question that is not hard to answer. For a long time mutations have been associated with genetic diseases. Knowing what change in the genome  underlies a disease can help us treat the disease if possible, it also allows us to screen other family or community members for the same change. Testing of phenotypically normal individuals is usually referred to as carrier screening and it is gaining popularity. The main reason behind this is not just our improved genetic knowledge. More women have children later in their lives, frequently only a single child, and also frequently they turn to IVF for conceiving, and not surprisingly they want to have healthy children. One way of ensuring better odds of having healthy offspring is to undergo a carrier screening before conception in addition to traditional test for chromosomal abnormalities, such as Down syndrome or DiGeorge syndrome.

Who should get tested?

Some doctors would recommend that all women considering conception should get screened for carrier status. A more conservative approach is that only women with known family history of genetic disease, or those from certain ethnic groups should get screened for carrier status of particular mutations. There are pros and cons to both approaches. A universal screen for everyone with current tools we have will not be as effective as we might think, but will definitely help to identify a large number of carriers of most prevalent mutations. ACMG and ACOG created a panel of genes and mutations recommended for screening in all populations (CFTR, SMA) and in individuals of Ashkenazi Jewish descent (CTFR, SMA, Canavan disease, familial dysautonomia, Tay-Sachs, Bloom Syndrome, FANCC, Gaucher disease, mucolipidosis type IV and Niemann-Pick type A disease). You may want to ask what about other ethnic groups? Are there diseases beyond cystic fibrosis  or spinal muscular atrophy that can be screened for in a particular ethnic group? Yes, beta-thalasemia and sickle cell anemia has high incidence in Mediterranean, Asian or African heritage/ancestry and those populations can benefit from carrier screening and prenatal diagnostics.

How should you get tested?

There are many ways you may want to go about getting tested. The best way is to discuss the issue with your partner and then with your doctor. If you wish ask to be referred to a genetic counselor, who will be able to advice you what test is best for you and will be able to help you understand the results once the test is completed. With the advances in genetics and diagnostics there are numerous tests available. There are multi gene panels, ethnic oriented tests, gene and mutation focused tests, syndrome oriented panels, sequencing or re-sequencing panels, PCR tests, whole gene sequencing, whole exome sequencing, whole genome sequencing… Picking what is best for you is not a decision you can make easily on your own, so do ask for some help.

I got tested and do I have 100% assurance that my child is going to be healthy?

No, the likelihood of the child being healthy is very high if you are not a carrier, have no family history of any genetic disorders and are not related to your partner. However, not all genetic diseases are passed on by parents, there are also “de novo” mutations, frequently dominant ones, that arise randomly in any individual, independent of their sex, ethnicity or family history. Carrier screening assures that you do not carry most common mutations for the most frequent genetic diseases and will not pass those to your children. Prenatal screening on your unborn baby, unless it is a whole genome sequencing, will be very similar and will screen only for a set of most common diseases. Once a child is born, most countries offer newborn screening with various number of conditions screened for by a variety of methods. Again these are not comprehensive tests, but they allow to identify newborns with most common disorders within the first few weeks of life. This often allows immediate intervention, for example by correcting the diet and the child grows up normally into a healthy adult. If the child is born with a genetic disorder that has not been identified, the diagnosis can be performed by sequencing to determine what is the cause of the disease. This knowledge can be later used to screen family members for carrier status.

Is this screening ethical?

This is a question that comes up all the time in any discussions about genetic testing. There is not a good or bad answer to it. In standard genetic disease screening test we are not trying to identify or pick specific characteristics of a baby, we are trying to prevent a possibility of a serious or lethal disease in a child. In many cases the screening can help to keep the child alive and well. Yet the tests can also be used in IVF embryo selection and what are ethical implications of that is a topic for a separate discussion.