When Renwick et al. categorized patients with family histories of breast cancer, it emerged that known AT-causing variants were associated with only a moderate increase in breast cancer predisposition [ 202].
For mutations that increase disease predisposition in both sexes, the imbalance in selection pressures can greatly increase the effect of the allele within the sex that experiences a greater fitness cost of carrying the allele.
Moreover, SNPs which can increase disease predisposition in colorectal cancer (HPNCC gene and MCAK gene) [ 31, 32], haemoglobinopathies (beta-globin gene) [ 33], and breast cancer (BARD1 gene) [ 34] have been predicted in computational studies.
Mutation in any of the four components of the NADPH oxidase complex, as is the case in patients with chronic granulomatous disease (CGD), leads to deficient production of superoxide ions, hydrogen peroxide, hydroxyl anions and hypohalous acid, resulting in increased predisposition to recurrent bacterial and fungal infections [5], [6], [7].
In mice, disruption of either p19Arf (the orthologue of human p14ARF) or p16Ink4b, or both, results in increased predisposition to tumour development [ 18- 21].
The increase in bone density weakens the bone, resulting in predisposition to fractures and osteomyelitis.
Epidemiological and animal studies have shown that adverse environments or suboptimal nutritional conditions during pregnancy can alter the physiology of offspring and increase their predisposition to many diseases in adult life.
A hypothesis of innate axial myofascial hypertonicity was derived as a possible contributor to increased biomechanical predisposition in AS [ 1, 2, 8].
With the improvement of life expectancy, it may be apparent that the patients of Williams Beuren syndrome may have an increased tumour predisposition in the near future.
Over the last few years, there has been a noticeable increase in efforts to identify genetic predispositions that modify the detection of the pathogen by the host or the resultant systemic reaction, efforts that may enhance our understanding of this syndrome.
