Prevalence gradients of Friedreich's Ataxia and R1b haplotype in Europe co‐localize, suggesting a common Palaeolithic origin in the Franco‐Cantabrian ice age refuge

Abstract

Combining data from epidemiological studies in Friedreich's Ataxia (FRDA) and patient organization membership lists, shows that FRDA prevalence exhibits large regional differences in Europe with a prevalence gradient from west to east. Highest levels are observed in northern Spain, south of France and Ireland, lowest levels in Scandinavia and Russia. The observed distribution of FRDA in Europe co-localizes with the gradient of the chromosomal R1b marker as detected within west Europe. This gradient is either derived from Palaeolithic migrations out of the Franco-Cantabrian Ice age refuge or from Neolithic migrations entering west Europe with the advance of agriculture. FRDA prevalence may have been increased in this population anytime after its separation from the closely related R1a carrying group. East European populations with a high frequency of the R1a marker show 10 fold lower prevalence of FRDA, indicating that the FRDA mutation was present in the common ancestor and was increased in the R1b carrying group. The FRDA carrying population went through a Palaeolithic population bottleneck supporting the view that the observed FRDA distribution and potentially the R1b distribution are derived from Palaeolithic migrations out of the FrancoCantabrian ice age refuge.

Friedreich Ataxia: current status and future prospects

“…Epidemiological studies gave evidence of a west to east prevalence gradient in Europe with highest levels in the South of France, North of Spain and Ireland and lowest levels in Scandinavia and Russia [3]. Carrier frequencies vary between 1:55 (North Spain) and 1:336 (Russia) [3]. Human Y chromosome haplotype analyses point to a Franco-Cantabrian ice age refuge origin of the FA carrying population [3].…”

“…Carrier frequencies vary between 1:55 (North Spain) and 1:336 (Russia) [3]. Human Y chromosome haplotype analyses point to a Franco-Cantabrian ice age refuge origin of the FA carrying population [3]. FA is rare in sub-Saharan African populations and very rare in the Far East.…”

“…Nerve conduction studie s reveal signs of an axonal sensory neuropathy with reduced or absent nerve action potentials typically first present in the sural nerve. Cortical potentials of somatosensory evoked potentials are delayed or absent [3]. …”

Targeting lipid peroxidation and mitochondrial imbalance in Friedreich's ataxia

“…It is an autosomal recessive disorder found mainly in Caucasians (Richardson et al, 2012), with a prevalence in the European population of 1: 50,000 (Velasco-Sánchez, 2011; see review Wilson, 2012). However, this ratio may vary depending on the population studied (Vankan et al, 2013). The disease is characterized by a progressive sensory and cerebellar ataxia, as both proprioceptive and spinocerebellar fibers are lost (Velasco-Sánchez et al, 2011;Parkinson el at., 2013).…”

Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism

“…Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia, with a prevalence of two to four individuals per 100,000 in Caucasian populations (Lopez-Arlandis et al, 1995; Vankan, 2013). Both the peripheral and central nervous systems are involved.…”