What might be the explanation for 'missing heritability'? What explains this gap in our understanding?
The gene hunters have assumed that traits such as height and common diseases such as diabetes are caused by genetic differences that are common in the population. Many of the ways in which these diseases are modelled have assumed that they result from combinations of these common variants; that is, each contributes relatively small effects to the risk of the trait developing. To date most research has focused on DNA variants that are present in over 5% of the population, often only with markers developed within populations of European ancestry. However, it might be that rare variants actually contribute large amounts of the risk. If rare variants are responsible then researchers will have missed genes.
A separate possibility is that other genetic differences not examined in the current DNA tests (which detect primarily single changes in DNA letters) might contribute risk. As knowledge of the human genome has developed we have learned that it is a very dynamic place, with large chunks of DNA changing rapidly between generations. These changes, called structural variants, are known to have associations with conditions such as autism and schizophrenia and it is possible that they could contribute more widely to many traits.
Finally, with complex traits we know that the effects of multiple genes and multiple environmental influences come together to contribute to that trait. However, we currently have only a limited understanding of gene-gene interactions, and gene-environment interplay.
What do you think?
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