Genetic admixture of European FRDA genes is the cause of Friedreich ataxia in the Mexican population.
Friedreich ataxia accounts for approximately 75% of European recessive ataxia patients. Approximately 98% of pathogenic chromosomes have large expansions of a GAA triplet repeat in the FRDA gene (E alleles), and strong linkage disequilibrium among polymorphisms spanning the FRDA locus indicates a common origin for all European E alleles. In contrast, we found that only 14 of 151 (9.3%) Mexican Mestizo patients with recessive ataxia were homozygous for E alleles. Analysis of polymorphisms spanning the FRDA locus revealed that all Mestizo E alleles had the common European haplotype, indicating that they share a single origin. Genetic admixture levels were determined, which revealed that the relative contributions to the Mestizo FRDA gene pool by Native American and European genes were 76-87% and 13-24%, respectively, commensurate with the observed low prevalence of Friedreich ataxia in Mestizos. This indicates that Friedreich ataxia in Mexican Mestizos is due to genetic admixture of European mutant FRDA genes in the Native American gene pool that existed prior to contact with Europeans.
Gómez
Mariluz
M
Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, 975 NE, 10th Street, BRC458, Oklahoma City, OK 73104, USA.
Clark
Rhonda M
RM
Nath
Swapan K
SK
Bhatti
Saeeda
S
Sharma
Rajesh
R
Alonso
Elisa
E
Rasmussen
Astrid
A
Bidichandani
Sanjay I
SI
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D015331:Cohort Studies; D005621:Friedreich Ataxia / Q000208:ethnology* / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008800:Mexico / Q000208:ethnology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D044465:White People / Q000235:genetics
C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins