In life, we can sometimes disregard genetics. We can think of disease in terms of environmental factors, and think the argument of ‘It’s just the way I was made’ as an excuse. We can think that fat people are that way because they eat too much, and smokers have got cancer from smoking, and in a lot of cases it is the truth. However, all of us know exceptions. Maybe a elderly relative you know smoked right up until the age of 92, then died from a non-smoking related illness. On the other hand, we can also feel helpless to our genetics. We can feel that we weren’t born fast and sporty, or weren’t born smart. But we all know exceptions to this rule too. Just take any para olympic champion. Many of these athletes have been born without properly formed legs, but managed to get to a level of physical fitness where they can out perform much of the world’s able bodied population. In some cases these people have gone on to beat top athletes, such as Oscar Pistorius, who became the first amputee to win an able bodied track world medal. Despite having been born without properly formed legs, thus having the genetic odds of winning a world track medal heavily stacked against him, Pistorius was able to achieve the impossible through a combination of blades, training, and hard work.
Unfortunately, when it comes to our health, there is no one-size-fits all answer to long life and fighting disease. Due to our genetics, it is different for different people! Different levels of different nutrients and foods can effect us in different ways. And across the global population, we have some people carrying some very interesting and unusual genetic defects. Although we do not know cures and treatments for all of these, they can be elightening and useful to us. Digital Image Processing, technology used for building images from MRI and CAT scans, was originally development for computer enhancement of moon landing pictures (http://www.nasa.gov/offices/ipp/home/myth_mri.html). Similarly research of genetic disorders may lead to helping us cure other diseases, or create technology that has other useful applications. Let’s look at some of the most weird and wonderful genetic disorders:
Gorlin Syndrome – Originating from a mutation in the PTCH1 gene, Gorlin Syndrome is a disorder which makes sufferers susceptible to some types of cancer. Our bodies use the PTCH1 gene to make a protein called Patched-1, which limits the growth of rogue cells. When we have a mutation of our PTCH1 gene and a protein called Sonic Hedgehog comes along, our Patched-1 protein keeps the Sonic Hedgehog protein in check, stopping unlimited cell dividing. However in people with Gorlin Syndrome, the Sonic Hedgehog protein causes the cells to turn bad and divide, and divide, and divide, causing a cancerous tumour.
Laron Syndrome – In many ways the opposite of Gorlin Syndrome, Laron’s syndrome is a certain type of dwarfism, caused by a variant of the growth hormone receptor. Most physicians believe that dwarfism is due to a lack of the growth hormone, which causes a surge in height in people during their teenage years. In the late 1950s, an Israeli endocrinologist named Zvi Laron discovered some patients who had an exception to that rule. Despite showing typical signs of dwarfism, ie, stunted growth, prominent forehead, and sunken eyes; the patients did not have a lack of GH in their blood, in fact they showed high levels of it. This indicates that rather than having dwarfism due to a lack of the Growth Hormone, it was instead due to their cells having an insensitivity to it. These people who had what became to be known as Laron’s syndrome, also had virtually no risk of developing diabetes or cancer.
HLTS and HLTRS – Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is an extremely rare condition only affecting less than 12 people currently world wide – a syndrome so rare that googling ‘HLTS’ returns no results. It arises from a mutation in the SOX18 gene, which leads to a faulty lymphatic system. This leads to extreme inflammation, hair loss, and small dilated blood vessels on the surface of the skin. The mutation in the SOX18 gene is recessive, so you will only have it if both your parents are carriers. Carriers show no symptoms, and the mutation is extremely rare, which is why so few people in the world have the syndrome. However, one sufferer of the syndrome was discovered, who also had kidney failure. Although this could have been a coincidence, some doctors may have thought it was linked. So they set about finding another HLTS sufferer who had kidney failure, and after many years found one. Although both of these HLTS sufferers with kidney failure were not related, they looked very alike. Their genes were tested, and they found that rather than having two defective SOX18 genes, they only had one! By all accounts, they shouldn’t have had HLTS at all, and should just have been carriers. This was named a new disease – HLTRS (Hypotrichosis-lymphedema-telangiectasia-renal syndrome). Scientists are still looking for a biological reason for the link between the single mutated SOX18 gene and renal failure.
CAH and Kathoeys – Congenital adrenal hyperplasia is a condition which starts when a baby is developing. If they do not make enough of the hormone Cortisol, then their adrenal glands are stimulated to try to make more. However, rather than just making more Cortisol, the adrenal gland also makes more of some sex hormones, which can cause a female to born born looking externally male. Research into some unusual conditions where somebody is born without a clear gender, has caused scientists to look more into what causes us to become male or female. Some unusual cases have caused scientists to realise what determines gender is far more complicated than the traditional idea of either XX or XY chromosomes. Since originally discovering the role of XX and XY chromosomes, we have been able to look at our chromosomes in much higher resolution, which has led to changes to new discoveries. A good example of this is Kathoeys – what transgender people are called in Thailand – where they number approximately 200,000.
Photo Credit Wikipedia: – “Agouti Mice” by Randy Jirtle and Dana Dolinoy – E-mailed by author. Licensed under CC BY 3.0 via Wikimedia Commons – http://commons.wikimedia.org/wiki/File:Agouti_Mice.jpg#/media/File:Agouti_Mice.jpg
Randy Jirtle and Agouti Mice – Randy Jirtle’s experiment with Agouti mice is a great example of how a single environmental factor can affect your genome. Randy proved by lab experiments that supplementing mice’s diets with methyl donors such as folic acid and vitamin B12 altered agouti mice’s coat colour and their susceptibility to obesity by altering their genome. This study was instrumental in demonstrating that nutritional, physical, and chemical factors could modify a human being’s epigenome.
SCN9A gene and the importance of pain – The SCN9A gene is a gene which can have an affect on what goes in and out of cells. Some of our cells have something which could be described as a gate on their surface which determines what goes in and out. A mutation in the SCN9A gene can lead to a condition called Congenital Insensitivity to Pain. Sufferers of this often damage and injure themselves by chewing through their own tongue, and mutilating parts of their body, as in some cases, they feel absolutely no pain at all. Geneticists have found mutations of the SCN9A gene in sword swallowers and human pincushions in India.
Royal Jelly – In a bee hive, when the old queen bee either becomes ill or dies, the worker bees choose several small larvae and house them in specially constructed queen cells. The worker bees then feed them with copious amounts of Royal Jelly. The bee which grows the strongest and quickest then makes its way out of it’s queen cell when it is big enough, and kills the other bees growing in the queen cells. What is interesting about this process is the consumption of Royal Jelly triggers the development of queen morphology, which includes fully developed ovaries, giving the queen the ability to give birth to large volumes of offspring. This was one of the earliest proofs of epigenetic effect of environmental factors. The change is due to an epigenetic modification of the DNA specifically due to the protein Royalactin contained in the Royal Jelly.
PKU / OTC Deficiency (page 104) – PKU, also known as Phenylketonuria, is the condition where due to a lacking metabolic process, you are unable to break down the chemical phenylalanine, which is found in hundreds of protein rich foods. People who are born with PKU, build up large amounts of phenylalanine in their blood which ultimately becomes toxic to their brains. Throughout their childhood they can go from developing normally, to having a severe intellectual disability due to this build up. The process is irreversible, but can be avoided by following a special diet developed by scientist if started early enough. A scientist called Robert Guthrie developed a method for testing for PKU at birth, now known as ‘Guthrie Cards’, whereby a small drop of blood is taken from a newborn’s heel at birth for testing. If identified early it is easy to completely prevent this intellectual impairment!
PTSD – Recently, scientists did a study of a large group of identical twins. They tracked them from birth, and throughout their life, there were some cases of the twins, where one was bullied and the other wasn’t. Tracking these twins right through to adulthood, they put the twins in a pressurised situation where they were likely to have a heightened stress response. From testing the twins, they found that the twin who had been bullied as a child had a muted cortisol response. This is due to an epigenetic change which is likely heritable from one generation to the next. There is already evidence to suggest that children of mothers suffering from PTSD have a more abnormal reaction to stress than their mothers. Couple this with experiments with animals, and we have some strong evidence that the epigenetic effects of exposure to large amounts of stress, can cause inheritable characteristics from one generation to the next.
FASD – Fetal Alchohol Spectrum Disorder, is perhaps one of the clearest example of how an environmental factor can affect your, or your children’s, genetics. People with FASD may have a smooth philtrum, smooth upper lip, and small wide apart eyes. In more severe cases people may have stunted growth, a damaged central nervous system, and intellectual disability. FASD is caused by the mother drinking shortly before or during pregnancy.
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