Moreover, use of the techniques pioneered by Cutting and his colleagues may lead to identification of modifier genes that play roles in other complications of CF, such as lung function, and in other diseases caused by a single gene, such as Huntington's disease.
However, it has become increasingly apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of Mendelian disorders, reflected for instance by intrafamilial variations, incomplete penetrance, and varying severity of the clinical course.
The mechanisms responsible for the determination of phenotypes are still not well understood; however, it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of Mendelian disorders.
These studies strongly suggest that ethanol interferes with the ability of differentiating cells to recruit epigenetic modifiers to genes playing key roles in development and to execute the molecular programs governing cellular differentiation.
The reason for this is undoubtedly multifactorial, including environmental, microbiological and socioeconomic factors, as well as adherence with treatment, with modifier genes also playing a role [ 86– 86].
Strong correlations also exist between (CTG n CAG n repeat length and the occurrence of Huntington disease [ 38, 39], although second site modifier genes and epigenetic mechanisms play a significant role in the appearance of HD symptoms.
We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative.
A 'major gene' is defined as a gene harbouring, a variant which is associated with a high lifetime risk for a disease; modifier genes and environmental factors additionally play a role in the aetiology of the respective diseases [ 45– 45].
Moreover, the admixture of ethnic groups plays an important role in the characterization of modifying effects, as modifier genes are diverse in different ethnicities and their complexity increases in ethnically admixed populations according to the extent of gene flow.
