Familial occurrence remains the single strongest factor to account for variation in disease risk. Genotype-phenotype relationships have been central to many studies of heritable traits. These studies help elucidate that an individual affected with a genetic disease or condition dramatically increases the risk for everyone else in the family. Finding these specific genes proves difficult, hence 'missing heritability '.
This study involving chromosomes substitution strains (CSS) of mice as model organisms tested both the frequency of the affected traits and the strength of their phenotypic effects by observing the genetically inherited phenotypic effects from the father's Y chromosome on female offspring. Because daughters do not inherit their fathers' Y chromosome, any traits that are attributable to the Y must be transgenerational rather than convention! al inheritance. The carefully selected chromosome substitution! method allowed for the control of potentially confounding genetic, social and environmental factors .
"A CSS is made by substituting a single chromosome from a donor strain on an inbred host strain. The resulting strain is identical to the original inbred host strain except for homozygosity for the substituted chromosome"
Daughters (XX) do not inherit the Y chromosome and therefore should not share the phenotype of CSS fathers. However results from this study found that although daughters were genetically identical to females from the host strain, their phenotype is attributed to this transgenerational genetic effect. In this first test for the generality of heritable epigenetic changes, the authors found that the frequency and strength of phenotypic effects resulting from transgenerational and conventional inheritance were comparable in frequency and strength, suggesting that this unconventional mode of inheritance rivals conventional genetics in its impact on biological variation and disease risk.
