Genetic assessments in infertile men: true abnormalities or polymorphisms?

Abstract

Genome structure and functioning make that variations in
DNA sequence may have different phenotypic effects. Insertion
or deletion of one base pair will lead to dramatic changes in
protein structure whereas substitution of one base pair for
another can lead to variable clinical consequences and may be
even neutral. Determining the pathological role of a mutation
needs to verify if it segregates with the disease in a family and
not to find it in healthy people, to use specific software predicting the functions of the mutated protein and to use functional
tests for knowing if this latter has still a biological function
or not. Bypassing these steps may lead to misunderstandings
or mistakes. As an example, a particular haplotype within the
USP26 gene, which had been associated with azoospermia,
is actually an ancestral allele which is frequently encountered
in Africa. In the same way, balanced structural chromosome abnormalities, like translocations, or Y chromosome microdélétions, which are frequently diagnosed in infertile patients,
may also be observed in normospermic men.