Oligogenic inheritance (Greek ὀλίγος – ὀligos = few, a little) describes a trait that is influenced by a few genes. Oligogenic inheritance represents an intermediate between monogenic inheritance in which a trait is determined by a single causative gene, and polygenic inheritance, in which a trait is influenced by many genes and often environmental factors.[1]
Historically, many traits were thought to be governed by a single causative gene (in what is deemed monogenic inheritance), however work in genetics revealed that these traits are comparatively rare, and in most cases so-called monogenic traits are predominantly influenced by one gene, but can be mediated by other genes of small effect.[2]
Around the 1930s/40s, evidence that multiple genes could affect the risk of disease that showed discrete inheritance patterns, due to differences in the age of onset of disease for siblings. The age of onset for sibling pairs was very similar, but between pairs of siblings could be quite different, and would in some cases cluster into several age brackets. This suggested a major gene that controlled the risk for a disease, and other genes that impacted age of onset.[3]
The recognition of diseases which were influenced by more than one gene highlighted a need to develop methodologies for detecting these oligogenic inheritance patterns, as they did not fit the more straightforward Mendelian model of inheritance. The developments of such methods accelerated the discovery of other examples of oligogenic traits, and sparked a change in the way genetic disease was perceived.[1]
One example of oligogenic inheritance is a case where one gene is sufficient to cause a trait, however its penetranceorexpressivity is influenced by another gene, called a modifier. An example of such a case is the gene TGFB1 which modified a person's risk of developing Alzheimer's disease if they are carrying the disease variant of the gene APP. The mechanism is thought to work through the modifier variant increasing the clearance of amyloid fibers in the aging brain, reducing plaque burden.[4]
A trait can be recognised as oligogenic through the following lines of evidence:[1]
| Dominant | Recessive | References |
|---|---|---|
| Widow's peak | Straight frontal hair line | [5][6] |
| Facial dimples * | No facial dimples | [7][8] |
| Able to taste PTC | Unable to taste PTC | [9] |
| Unattached (free) earlobe | Attached earlobe | [7][10][11] |
| Clockwise hair direction (left to right) | Counter-clockwise hair direction (right to left) | [12] |
| Cleft chin | Smooth chin | [13] |
| Ability to roll tongue (Able to hold tongue in a U shape) | No ability to roll tongue | [14] |
| Extra finger or toe | Normal five fingers and toes | [14] |
| Straight thumb | Hitchhiker's thumb | [14] |
| Freckles | No freckles | [7][15] |
| Wet-type earwax | Dry-type earwax | [10][16] |
| Shortness in fingers | Normal finger length | [14] |
| Webbed fingers | Normal separated fingers | [14] |
| Roman nose | No prominent bridge | [17] |
| Marfan's syndrome | Normal body proportions | [18] |
| Huntington's disease | No nerve damage | [19] |
| Normal mucus lining | Cystic fibrosis | [20] |
| Forged chin | Receding chin | [17] |
| White forelock | Dark forelock | [21] |
| Ligamentous angustus | Ligamentous laxity | [22] |
| Ability to eat sugar | Galactosemia | [23] |
| Total leukonychia and Bart pumphrey syndrome | Partial leukonychia | [24] |
| Absence of fish-like body odour | Trimethylaminuria | [25] |
| Lactose persistence * | Lactose intolerance * | [26] |
| Prominent chin (V-shaped) | Less prominent chin (U-shaped) | [27] |
