Unique local genetic problem needs a unique local solution

In the South African black population, it is almost as common as albinism, but the standard genetic test used to detect it is useless for almost half of black people with SMA.

Just as South Africans have a colourful physical history, they have a unique genetic composition. Southern Africa is thought to be the birthplace of the human species, with the Khoisan having the world’s oldest known genetic profile. Many different groups, after having left the Cradle of Humankind, migrated back to the southern tip of the continent over time. 

This means that South Africa has a high frequency of the Founder Effect, which is when a small group of individuals from a larger population migrate and inhabit a new area. The frequency of certain traits such as disease could increase in this group due to a lack of genetic diversity and inbreeding. Some South African examples include the frequency of high cholesterol among the Afrikaner population, albinism (lack of pigment) in the black population, beta-thalassaemia (a blood disorder that causes anaemia) in the Indian population and Tay-Sachs disease (a wasting disease which causes severe nerve damage) in the Ashkenazi Jewish population.

Genetics has been the inspiration for many horror movies and superhero origins and, due to sensational headlines, the term “genetics” has become synonymous with controversial topics such as gene patenting, stem cell therapy, genetically modified food and human cloning. But diagnostic testing for genetic diseases plays an underappreciated and essential role in modern medicine. The diagnosis of a genetic disease in a family could assist with the management of the disease and help the family to make informed reproductive choices. 

The human genome consists of 3.2-billion nucleotides or letters of code. Mutations or changes in this code could have a spectrum of consequences, from no effect whatsoever, to preventing a gene from functioning properly and causing disease. In complex diseases such as diabetes, cancer and schizophrenia, many different genes interact with one another and the environment. With recent advances in technology, it has become possible to screen the entire human genome for clues about who is likely to suffer from what diseases and to what extent. 

The Division of Human Genetics at the National Health Laboratory Service (NHLS) in Johannesburg is the largest referral lab for medical genetic testing in South Africa. Its research is largely aimed at increasing our knowledge about the genetic make-up and diseases of South African populations. 

Due to the unique genetics of South Africans, novel testing strategies have to be developed to identify previously unreported and founder mutations in common genetic disorders. Spinal muscular atrophy (SMA) is one of these diseases. 

SMA is a neuromuscular disorder characterised by muscle wasting, weakness and paralysis, and there is currently no cure. 

Survival depends on the severity and the rate of deterioration of the disease. Interest in SMA was sparked recently when a South African woman in the United Kingdom was charged with the murder of her three children afflicted with SMA.

The disease is caused by mutations within the survival motor neuron 1 (SMN1) gene. The protein that this gene codes for is necessary for the survival of motor neurons, which control our muscles. These neurons are located in the spinal cord and brain stem. 

For a person to get this disease, they need to inherit two copies of an SMA mutation, one from each parent. A person who has only one copy of a SMA mutation will not be affected, but will be a carrier of the disease (meaning they can pass it on to their children). If both parents are carriers of an SMA mutation, they have a one in four chance of having an affected child.

The birth incidence of SMA in the black South African population is 1 in 3 574 with a carrier rate of 1 in 50. If Soccer City was filled to capacity with black South Africans (about 94 700 people), then 27 people in the stadium would be affected with SMA and 1 900 people would be carriers of SMA. 

A common mutation, a deletion of a part of the SMN1 gene, is found in 95% of SMA patients worldwide. The birth incidence of SMA in white South Africans is high at one in 1945, and this common mutation has been observed in 95% of white South African SMA cases. But this particular mutation is only found in 51% of black South African SMA cases. The standard diagnostic assay used for SMA testing is targeted at detecting this common mutation, meaning that a diagnosis of SMA cannot be confirmed in almost half of black SMA families tested. 

Research is under way at the NHLS, in association with the University of the Witwatersrand, to investigate the molecular basis of SMA and the disease mechanism in the black South African population further. 

Research will be performed on both a DNA and RNA level. Whereas DNA represents the blueprint of the human genome, RNA acts as the messenger, transporting a copy of the blueprint to various sites of the body. Looking at mutations in both the DNA and RNA code will help us to understand how mutations affect the SMA protein.

This research could potentially lead to improved diagnostic, carrier and prenatal testing and accurate genetic counselling for the 49% of black South African people who are affected by SMA, but who test negative for the common deletion mutation. Understanding the basic molecular mechanisms of disease in South Africa could eventually lead to therapies that are specifically designed for South African populations. This is particularly important because therapies that work in developed countries might not be as effective for South Africans due to our unique genetics.

For more information, visit the Muscle Dystrophy Foundation of South Africa’s website www.mdsa.org.za.

Elana Vorster is a MSc candidate at the University of the Witwatersrand.


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