Genetic predisposition to common disorders

In many cases, a single defective gene is not sufficient to cause a disorder. Yet many of the common diseases of adult life, such as diabetes mellitus, hypertension, schizophrenia, and most common congenital malformations, such as cleft lip, cleft palate, neural tube defects, have a strong genetic component to their occurrence. In these examples it is thought that a large number of genes each act in a small but significant manner to predispose an individual to the genetic condition. 

Polygenic genetic disorders are those which are caused by the impact of many different genes, each having only a small individual impact on the final condition. Multifactorial traits are those which result from an interaction between multiple genes and often multiple environmental factors.

Which disorders are polygenic and which are random?

Many multifactorial or polygenic traits do not stick to the classic Mendelian manner of inheritance and therefore, their genetic component can easily be missed. However, scientists have been able to separate the random from the genetic by inspecting the occurrence of disorders in identical (mono-zygotic) versus non-identical (di-zygotic) twins. Remember than monozygotic twins are genetically identical and dizygotic twins are not. As shown in the table below, in many conditions, the chance of both monozygotic twins being affected by the same disorder is much higher than dizygotic. This infers that a strong "non random" or genetic component is in play.

Table showing twin concordance for common disorders

Although that it can clearly be seen that a genetic component is at play in these conditions, hunting down these genes can be a very long and arduous task. To find and sequence a gene scientists must first be able to distinguish a gene that may have a predisposing power on a disorder from others that may not. Yet in a disease that may be due to 40 genes and be 40% genetic and 60% environmental in its occurrence, it is likely to be very hard to see that single gene in amongst the others.

Families with strong links to specific diseases are often very useful to the scientists hunting for specific genes, especially when some other trait is associated (say the red-headed members of the family are more likely to develop the disorder). Another clue might be provided by a chromosomal abnormality in the family (where the normal gene may have been broken or disturbed).

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