Genetic tests and personalised medicine

By Grant Jacobs 20/11/2009

How will genomes and direct-to-consumer (DTC) genetic tests affect medicine?

The Doctor, Luke Fildes (source: wikipedia)

Recently I wrote about an up-coming roundtable meeting to be held in Wellington looking at aspects of genomics, medicine and law. Over the next few days I will direct a few posts at the subject matter of this meeting.

A visit to the GP, redux

You head off to the GP. They hear your complaints, ask some questions, carry out a few tests. You are offered the remedy that works best for most people.

But is it the best remedy for you?

You try it. Perhaps it didn’t work as well as you’d hope. You go back and get recommended the second-best remedy.

Medicines are currently usually offered on the basis of what works best for most people, rather than testing the person to find what might work best for that particular person.

One hope of personalised medicine is that by testing a patient’s genetics doctors might be able to recommend to the patient the remedy that best suits their genetics.

An alternative, more controversial, scenario–looking towards a sci-fi styled future–is DIY diagnosis. Order your own genetic test results, read what they say and act. This can’t apply to infectious diseases or injuries, but for disorders that are mostly genetic it’s already making it’s way onto the market. Rightfully or wrongfully direct-to-consumer DTC genomics carries some aspects of DIY. Will it cause more DIY disasters, like the over-confident home renovator?

Not new or a “revolution”, an evolution of existing practice

Genetic testing for medical purposes isn’t new.

Biochemical testing for genetic disorders has been around for at least 50 years. These older tests aren’t based on DNA sequencing, but usually on testing for chemicals or particular proteins (enzymes) in urine or blood.

A good example is the heel prick testing for phenylketonuria (PKU) done shortly after birth. In this disease patients lack or have a dysfunctional phenylalanine hydroxylase enzyme, that is required in order to convert the amino acid phenylanine to tyrosine. With early diagnosis this condition can be managed to prevent brain damage and poor health.

Source: wikipedia

DNA-based genetic testing has been around for at least 10 years.

Examples of DNA-based genetic testing include some types of cancers (for example examining the BRCA1 and BRCA2 genes in breast cancer cases), Friedreich’s ataxia, and other diseases that have well-established genetic causes. A number of adult-onset diseases such as Alzheimer’s or Huntington’s disease can be screened earlier in life.

Confirming some diseases and following this with monitoring and management of the disease can be of use, for example in familial adenomatous polyposis, where monitoring and removal of excess colon growths can be used as treatment. There are other examples and I’ve listed more in the Appendix.

Genome-wide screening extends existing practice which tests specific conditions by looking at the DNA sequence of genes that are known to be associated with the specific disorder being tested to obtaining information about (almost) all of the DNA of the person and hence (almost) all genes. (I write ‘almost’ all, as no existing sequencing method truly obtains all the DNA sequence, some small parts of our genomes are difficult to DNA sequence.)

This means that in principle all possible genetic differences that could affect the disease or person can be examined, but there’s a catch: you need to know what to look for. What differences matter, and how much?

Why test?

Typical reasons for genetic testing include:

  • Screening people who carry disease-causing mutations that don’t cause disease in themselves, but might in their children
  • Embryo screening, e.g. for in vitro fertilisation
  • Prenatal testing
  • Screening newborn infants
  • Testing for adult-onset disorders or diseases earlier in life (e.g. Huntington’s disease, adult-onset cancers, Alzheimer’s disease)
  • Confirming a diagnosis
  • Identity testing, sometimes for forensic purposes (I hope our forensic scientist scibling can cover this sometime!)

One we could add, bearing DTC genomics in mind in particular, is tailoring your lifestyle to your genetics. In a sense this is a variant on testing for adult-onset disorders or diseases. (Most middle-aged people would say, that sagging stomach and general sloth is a disease, but I digress.)

In a following post, we will look at some of the many issues involved in genetic testing, in genome-wide approaches in particular. We’ll also have a closer look at direct-to-consumer genomics. Time permitting, I also hope to look at the role of people in my field, computational biology), as well as some science communication issues that might arise.

Further reading

Ricki Lewis’ article A Brief History of Genetic Testing offers an introduction to genetic testing. His article also introduces direct-to-consumer genetic testing.

The “Gene Testing” page on the Human Genome Project Information website is informative and has links to further articles.


I will add academic references later (time commitments!)

Appendix: Examples of genetic testing.

(Taken from the “Gene Testing” webpage* on the Human Genome Project Information website on 19-Nov-2009)

The presence of an asterix (*) indicates that this test provides the estimated risk only. This list might seem long, but it’s a very short list really when you consider that there are a lot of diseases with a genetic component for which there is no genetic test available.

  • Alpha-1-antitrypsin deficiency (AAT; emphysema and liver disease)
  • Amyotrophic lateral sclerosis (ALS; Lou Gehrig’s Disease; progressive motor function loss leading to paralysis and death)
  • Alzheimer’s disease* (APOE; late-onset variety of senile dementia)
  • Ataxia telangiectasia (AT; progressive brain disorder resulting in loss of muscle control and cancers)
  • Gaucher disease (GD; enlarged liver and spleen, bone degeneration)
  • Inherited breast and ovarian cancer* (BRCA 1 and 2; early-onset tumors of breasts and ovaries)
  • Hereditary nonpolyposis colon cancer* (CA; early-onset tumors of colon and sometimes other organs)
  • Central Core Disease (CCD; mild to severe muscle weakness)
  • Charcot-Marie-Tooth (CMT; loss of feeling in ends of limbs)
  • Congenital adrenal hyperplasia (CAH; hormone deficiency; ambiguous genitalia and male pseudohermaphroditism)
  • Cystic fibrosis (CF; disease of lung and pancreas resulting in thick mucous accumulations and chronic infections)
  • Duchenne muscular dystrophy/Becker muscular dystrophy (DMD; severe to mild muscle wasting, deterioration, weakness)
  • Dystonia (DYT; muscle rigidity, repetitive twisting movements)
  • Emanuel Syndrome (severe mental retardation, abnormal development of the head, heart and kidney problems)
  • Fanconi anemia, group C (FA; anemia, leukemia, skeletal deformities)
  • Factor V-Leiden (FVL; blood-clotting disorder)
  • Fragile X syndrome (FRAX; leading cause of inherited mental retardation)
  • Galactosemia (GALT; metabolic disorder affects ability to metabolize galactose)
  • Hemophilia A and B (HEMA and HEMB; bleeding disorders)
  • Hereditary Hemochromatosis (HFE; excess iron storage disorder)
  • Huntington’s disease (HD; usually midlife onset; progressive, lethal, degenerative neurological disease)
  • Marfan Syndrome (FBN1; connective tissue disorder; tissues of ligaments, blood vessel walls, cartilage, heart valves and other structures abnormally weak)
  • Mucopolysaccharidosis (MPS; deficiency of enzymes needed to break down long chain sugars called glycosaminoglycans; corneal clouding, joint stiffness, heart disease, mental retardation)
  • Myotonic dystrophy (MD; progressive muscle weakness; most common form of adult muscular dystrophy)
  • Neurofibromatosis type 1 (NF1; multiple benign nervous system tumors that can be disfiguring; cancers)
  • Phenylketonuria (PKU; progressive mental retardation due to missing enzyme; correctable by diet)
  • Polycystic Kidney Disease (PKD1, PKD2; cysts in the kidneys and other organs)
  • Adult Polycystic Kidney Disease (APKD; kidney failure and liver disease)
  • Prader Willi/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death)
  • Sickle cell disease (SS; blood cell disorder; chronic pain and infections)
  • Spinocerebellar ataxia, type 1 (SCA1; involuntary muscle movements, reflex disorders, explosive speech)
  • Spinal muscular atrophy (SMA; severe, usually lethal progressive muscle-wasting disorder in children)
  • Tay-Sachs Disease (TS; fatal neurological disease of early childhood; seizures, paralysis)
  • Thalassemias (THAL; anemias – reduced red blood cell levels)
  • Timothy Syndrome (CACNA1C; characterized by severe cardiac arrhythmia, webbing of the fingers and toes called syndactyly, autism)

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