Ever since genetic testing is made available to the general populace as a DTC (direct-to-consumer) service, it has become one of the hottest topics that often appear in serious medical documentaries and are even discussed over late-night TV talk-shows. What then does genetic testing serve besides tracking down perpetrators in crime and helping unite lost family members as seen in the movies?
Your Genes and You
To appreciate how genetic testing could influence our life, we first need to understand how we developed and grow biologically. Our body is made up of cells, each normally containing 23 sets of chromosomes that are made up of genes packaged as DNA strands. DNA provides specific instructions to our cells regarding how proteins, the building blocks of life, are made.
During conception, we receive one set of genes from each parent, totaling up to more than 30,000 different genes. These genes are found mainly in the nucleus of the cell, with exception of a small number of genes, mainly through maternal inheritance, residing in the mitochondria. Having said that, Y chromosomes are always inherited from the father only.
Genes contain instructions that determine how our body is supposed to function. We probably not survive till birth if we had fewer or excess chromosomes, except when an X or Y chromosome is missing which then give rise to a condition known as Turner Syndrome. However, when parts of chromosomes are missing, birth defects may occur and intellectual and/or physical development could be adversely inhibited. These are categorically known as chromosomal deletion syndromes.
The Science Behind Genetic Testing
Our genes when taken in totality forms a genome that gives us our unique physical traits and characteristics. Genes are designed to replicate consistently, and DNA remains unchanged throughout our life but at times, due to environmental and other exogenous influences, could result in changes in the DNA. These changes or variants in genes, chromosomes, and proteins are the premises for genetic testing.
In genetics, a single nucleotide polymorphism (SNP) is a variation or substitution at a single specific position in a DNA sequence or genome among individuals. Conceptually, there may be up to 4 different variations for every single position in the human genome ie. A (adenine), C (cytosine), G (guanine), and T (thymine). For example, at a specific base position, the C nucleotide may appear in most individuals, but the position can be occupied by an A in a minority of individuals. This implies that there is a SNP at this specific position with two possible nucleotide variations, C or A, and are alleles for this specific position.
Most SNPs are not responsible for a diseased state but they instead serve as biological markers for pinpointing a disease on the human genome map, as they are usually located near a gene found to be associated with a certain disease. SNPs pinpoint differences in our susceptibility to a wide range of diseases eg. β-thalassemia and sickle-cell anemia. Genetic variations caused by SNPs also reflect the severity of illness and predict the way our body metabolizes drugs and thus its response to treatment. These associations allow geneticists to look for SNPs to evaluate an individual's genetic predisposition toward disease development.
Within the genome, SNPs may be positioned in three possible areas - within the coding sequences of the genes, non-coding regions of the genes, or in the intergenic regions ie. between genes.
SNPs within a coding sequence do not necessarily change the amino acid sequence of the protein that is produced, due to redundancy of the genetic code. Whilst nonsynonymous SNPs in the coding region do change the amino acid sequence of proteins, synonymous SNPs (minor mutations) usually do not affect protein sequence.
Similarly, SNPs found outside protein-coding regions may still affect gene splicing, transcription factor binding, messenger RNA degradation, or the sequence of non-coding RNA. Gene expression affected by this type of SNP is referred to as an eSNP (expression SNP) and may be upstream or downstream from the gene.
How Genetic Testing May Benefit You
The Human Genome Project lists the following applications for genetic testing:
Pre-implantation genetic diagnosis (PGD) – is used to detect genetic changes or chromosomal disorders in embryos created via assisted reproductive techniques such as in-vitro fertilization. Only embryos without defects are implanted in the uterus to initiate a pregnancy.
Pre-natal – a non-exhaustive test that screens the fetus to detect changes in a fetus's genes or chromosomes before birth to assist a couple in making decisions about pregnancy by identifying specific inherited disorders and birth defects eg. Trisomy 18 or Edwards syndrome.
Neo-natal – screens infants just after birth for certain genetic disorders affecting development eg. phenylketonuria (a treatable genetic disorder that causes intellectual disability) or congenital hypothyroidism.
Carrier – carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. Individuals with a family history of a genetic disorder and people in ethnic groups, eg. the Jews, with a predisposition towards specific genetic conditions should subject themselves to carrier testing for family planning.
Diagnostic – when a particular condition is suspected based on clinical presentation, diagnostic testing is used to identify, confirm, or rule out the specific genetic or chromosomal condition. Though maybe performed at any point in time of a person’s life, it is however not available for all genes or genetic conditions. The findings from such a test are usually used to guide the management of the disorder.
Pharmacogenomic – provides information about how certain medicines are processed by an individual’s body. This is also the basis for personalized medicine.
Predictive testing – includes pre-symptomatic and predisposition testing. Used to detect possible gene mutations associated with disorders that often appear later in life, these tests help alert individuals with a family history of a genetic disorder yet without manifestations at the time of testing. Predisposition testing identifies mutations that predispose a person in developing disorders with a genetic basis, such as cancer. Pre-symptomatic testing determines whether a person will develop a genetic disorder with delayed onset, such as hereditary hemochromatosis (iron overload). The results of predictive testing can provide information about a person’s increased risk of developing a specific disorder and help with making decisions about pre-emptive medical care and preventive lifestyle changes.
In summary, genetic testing may be deployed in:
- uncovering insidious ailments in asymptomatic individuals with a family history of debilitating diseases, eg. cancers or neurological ailments; to understand the potential of their developing these diseases and thus enable these individuals to proactively manage their health guided by genetic information.
- assuring the health integrity of the potential family nucleus even before its formation. This may be achieved through carrier testing and prenatal testing, and where appropriate pre-implantation genetic diagnosis.
- perfectly healthy individuals who wish to take the guesswork out of weight loss and fitness initiatives by engaging in genotypematched dieting plans, exercise regimes, and rest schedules. People who leveraged genetic information in pursuit of life goals pertaining to physique, physical and even intellectual performances often realized quantum leap improvement.
Genetic Testing - The Genoplan Way
There are several considerations one may have to contend with in choosing a genetic testing kit:
Sensitivity – examining mutations in the genome directly is no assurance of high sensitivity as mutations at two or more genetic loci can produce the same or similar phenotypes. Heterogeneity occurs when a single clinical disorder is caused by several genes eg. mutations at either chromosome 9 (TSC-1) or chromosome 16 (TSC-2) that cause tuberous sclerosis. Location of promoters or other gene-controlling elements outside the portion of the gene being tested will substantially affect sensitivity too resulting in the test failing to identify affected individuals.
Specificity – A diagnosis is not always made by the presence of a DNA change. Some gene changes are harmless variants, and mutations in a single gene can sometimes cause several different diseases.
Interpretation – interpretation of genetic tests can be complex because:
- the effect of a given mutation may be modified by other genes and the environment,
- different changes in a gene may give rise to different results,
- intermediate alleles may cause disease in only a fraction of cases,
- a person with a “diseasecausing mutation” may appear unaffected, and
- other genes, environmental and individual factors such as age and gender can affect penetrance so that two individuals with the same gene change may have entirely different clinical presentations.
Genoplan is one of the more advanced yet cost-effective DTC genetic testing kits available in Singapore today. By collecting saliva and sending the sample postage pre-paid to Genoplan, users receive online reports within ten business days which is among the fastest of competing services that typically take four to six weeks to deliver results. The rapid turnaround is attributed to the use of New Generation Asian Screening Array.
Manufactured by AccuGene in Japan or Korea, the package tests for 500 items of interest for which 7,490 genes are examined to achieve higher sensitivity and specificity. Moreover, the analysis platform is oriented towards the use of 700,000 Asian Specific SNPs for benchmarking and disease risk profiling, giving greater relevance to the reported information.