Determining the Origin of Different Variants Associated with Familial Mediterranean Fever by Machine-Learning

Familial Mediterranean fever (FMF) is a common autosomal recessive autoinflammatory disease
caused by mutation in Mediterranean fever gene (MEFV). The five most prevalent mutations are
identified mainly among patients with northern African descent. Data regarding the association
between country of origin and mutation type are scarce, and therefore this study was conducted.
The goal our study was to establish a connection between a specific country of origin and the
mutation most likely to be found for an individual FMF patient. The data used in this study
included Jewish patients carrying a mutation in MEVF gene. Due to the ethnic mixing within the
Jewish population, a single patient rarely has a single country of origin for all four grandparents.
The M694V mutation was found to be the most common among the study population with
mutations E148Q and V726A being the second and third most common, respectively. Using
Machine learning approach, we have identified for each mutation type countries of origin that
increase or decrease the likelihood of carrying specific mutations: M694V in North Africa;
V726A in Europe; E148Q in west Asia.

Based on our results, it is possible to describe an association between the origin of the three most
common mutation types and a geographical region. Given the connection of ethnicity and
genetics, it stands to reason to hypothesize an evolutionary based theory regarding the emergence
of a specific FMF mutation in a particular region on the globe, such as offering an increased
resistance for endemic infectious agents.