|Image credit: Wikipedia|
A common example is Duchenne Muscular Dystrophy, caused in humans by a defective copy of the Dystrophin gene (DMD) that encodes the dystrohin protein. DMD gene is located on the X chromosome. Since, females in humans have two X chromosomes, one defective copy of the X chromosome makes the person a carrier for the disorder. Muscular Dystrophy usually does not affect females, unless she is the progeny of an affected father and carrier mother. However, males, who inherit only one X chromosome from their mother, have a 50% chance of getting the defective copy of the gene from a carrier mother and therefore are at 50% risk of being affected by muscular dystrophy. That's the thumb rule.
Meet Ringo, a male Golden Retriever, the exception!
|Ringo, the Golden Retriever, who has the mutation for Duchenne Msucular Dystrophy, but not the condition.|
Golden Retrievers are also susceptible to muscular dystrophy, called the Golden Retriever Muscular Dystrophy (GRMD), and are used as a model to further understand the disorder. Ringo's mum, Beth was a diagnosed carrier and when Ringo was born, his DNA was tested to know, if he would be affected. The test confirmed that Ringo was affected and so were two of his brothers from the same litter.
One of Ringo's affected sibling succumbed to the disorder at an early age while the other shows severe symptoms of the disease. Ringo, however, does not show any symptoms of the disease, even though, he does not produce any amount of the dystrophin protein and continues to lead a perfectly normal life.
Ringo's litter with other carrier females have puppies affected by the disorder. Suflair, is a male dog in Ringo's litter who has repeated history. When tested, Suflair too has same genetic defect as seen in other Golden Retrievers who have Muscular Dystrophy. Yet, Suflair, does not exhibit symptoms of the disorder. Such instances, humble scientists every time they occur. There is definitely something that has allowed these exceptional dogs to lead a normal life although they have genetic defects. Attempts to discover that 'something' have not yielded results. However, science is making progress in getting to know exactly what is our DNA capable of and how does it exactly function.
Whether, we will know in our life times, why Ringo and Suflair are exceptions, only time can tell!
Three years after this post was written, researchers at the Human Genome and Stem Cell Center at the University of Sao Paulo have published their findings about how Ringo and Suflair were able to defy the thumb rule and not show any signs of DMD. Using whole genome sequencing and transcriptome analysis, the researchers were able to identify over expression of another gene called Jagged1, a member of the notch signalling pathway, that plays an important role in cell development and homeostasis. Over expression of Jagged1 has shown to compensate the effects caused by the mutations in dystrophin gene in Ringo and Suflair and is therefore a potential target for future therapies for muscular dystrophy.
Although Ringo is no longer with us, his contribution will remain with us always!
Vieira NM, Elvers I, Alexander MS, Moreira YB, Eran A, Gomes JP, Marshall JL, Karlsson EK, Verjovski-Almeida S, Lindblad-Toh K, Kunkel LM, & Zatz M (2015). Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype. Cell, 163 (5), 1204-13 PMID: 26582133