If a parent has an autosomal recessive genetic/hereditary condition with a truncating mutation (more severe than non-truncating mutation), and the parent passes the gene to the child, will the child automatically get the truncating mutation? Or is truncating vs. non truncating more of a epigenetics type of thing that is determined by life style considerations?
truncating mutations are not necessarily more severe than any other type of mutation. For instance a point mutation creating a new splice site or destroying a cysteine bridge may change the shape of a protein more than truncation of an unimportant part of the gene and a single base insertion may change dozens of amino acids. In cases where there are many genes making similar products like globin genes loss of one gene may be compensated by products from other genes as seen in haemoglobinopathies but in general genes passed on from parents will have similar actions in the offspring although in many complex disorders like cleft lip the action of one mutation can be greatly modified by the actions of other genes and variants elsewhere on the genome. Another example of this is that in some areas the sickle cell mutation can be made to look quite benign by the simultaneous action of hereditary persistence of fetal haemoglobin when the existence of fetal HB stops the sickle HB from polymerising and ameliorates the symptoms
Thank you so much Paul! I am specifically researching Autosomal Recessive Polycystic Kidney Disease (PKD). I'm trying to understand the truncating gene concept in the context of this PKD disease. If a patient has a truncating pkd gene, statistics seem to indicate that the disease is more severe when compared to a non-truncating mutation. So my question is then, if a parent has the truncating pkd gene, does that definitively mean that the son who has the disease must also automatically have the truncating pkd gene? Or is it still possible for the son to have a non-truncating pkd gene? Trying to understand if truncating is passed on or more of an epigenetics thing where it depends on lifestyle factors.
since the disorder is AR then both chromosomes must have a mutation so unless one parent is affected ( not just a carrier) with a truncating and also another mutation then if the child is affected and one parent has a truncating mutation then I would say that this mutation must be transmitted except in the very rare case of the child getting the normal chromosome from that parent and a new mutation arising on the normal chromosome , My understanding is that this situation is classical AR genetics and does not have any association with epigenetics but I have almost no knowledge about PKD or cilliopathies so suggest that a considerable expert on PKD on this site is @Paul Winyard whose opinion I would trust on all questions related to PKD
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