Genetic diversity at the FMR1 locus in Mexican population.
BACKGROUND
Fragile X syndrome is the most frequent cause of inherited mental retardation; it is caused by expansion of CGG repeats in the first exon of the FMR1 gene. Number of CGG repeats varies between 6 and 50 triplets in normal individuals and the most common alleles have 29 or 30 repeats. Allelic patterns in the global population are similar; however, some reports show statistical differences among several populations. Distribution of allelic frequencies for FMR1 locus has not been reported in Mexican population.


METHODS
Determination of the CGG repeat number was achieved by polymerase chain reaction (PCR) on modified DNA from 129 unrelated Mexican mestizos (46 FRAXA-negative males with mental retardation and 83 healthy individuals). DNA modification by sodium bisulfite achieves conversion of unmethylated cytosine residues to uracil, which allows efficient amplification by single PCR. Methylation status of FMR1 region for each individual was also established. DNA sequencing of a number of amplified samples was realized to validate the procedure.


RESULTS
Molecular analysis of the FMR1 gene showed 23 different alleles. Statistical comparison of allelic length between healthy and affected individuals does not show significant differences. Trinucleotide repeat number varied from 16-40, with modal number of 32 (27.58%), second peak at 30 (25.28%), and minor peak at 34 (10.34%). Together, allelic distribution in the Mexican sample differs significantly from those reported for Caucasian, Chinese, African, Indonesian, Brazilian, Chilean, and Mixtec populations. An excess of large alleles (> or =34 repeats) was evident.


CONCLUSIONS
Allele distribution in FMR1 gene from Mexican mestizos is different from that of other reported populations around the world. This unusual modal pattern probably is related to the particular ethnic background of the Mexican population. On the other hand, PCR on modified DNA is a valuable and efficient method for determination of CGG repetitive sequences in FMR1 gene.
Rosales-Reynoso
Mónica Alejandra
MA
División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico.
Mendoza-Carrera
Francisco
F
Troyo-Sanromán
Rogelio
R
Medina
Claudina
C
Barros-Núñez
Patricio
P
D000483:Alleles; D016022:Case-Control Studies; D018899:CpG Islands; D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008800:Mexico; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013447:Sulfites / Q000494:pharmacology
D003596:Cytosine; D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D013447:Sulfites; C497683:FMR1 protein, human; C009279:sodium bisulfite