Lucila Sandoval

The C677T polymorphism of the methylenetetrahydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations.

The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene, associated with the thermolabile form of the enzyme, has reportedly been found to be increased in neural-tube defects (NTD), though this association is still unclear. A group of 107 mestizo parents of NTD children and five control populations: 101 mestizo (M), 50 Huichol (H), 38 Tarahumara (T), 21 Purepecha (P) and 20 Caucasian (C) individuals were typed for the MTHFR C677T variant by the PCR/RFLP (HinfI) method. Genotype frequencies were in agreement with the Hardy-Weinberg expectations in all six populations. Allele frequency (%) of the C677T variant was 45 in NTD, 44 in M, 56 in H, 36 in T, 57 in P, 35 in C. Pairwise inter-population comparisons of allele frequency disclosed a very similar distribution between NTD and M groups (exact test, P=0.92). Among controls, differences between M and individual native groups were NS (0.06<P<0.21), as it was between M and C (P=0.29). A high frequency of the variant was found in H (56%) and P (57%). A similar allele frequency in groups M and NTD does not support a causal relationship between NTD and parental MTHFR C677T genotypes. Thus, the C677T variant cannot be regarded as a major genetic risk factor for NTD in Mexican mestizo parents. Otherwise, C677T in Mexico is very frequent, especially in Huichol and Purepecha natives, as compared with other groups world wide.

Glucose-6-phosphate dehydrogenase (G-6-PD) mutations in Mexico: four new G-6-PD variants

Screening for mutations at the G-6-PD gene by PCR-SSCP combined with restriction enzyme analysis and DNA sequencing was performed in nine G-6-PD deficient individuals with negative results for the presence of the most frequent G-6-PD mutations previously observed in Mexican population. The variants G-6-PD Valladolid(406T), G-6-PD Durham(713G), and G-6-PD Viangchan(871A) and four new G-6-PD mutant alleles were identified. The new mutations are located at cDNA nt 376 A --> T (126 Asn --> Tyr), nt 770 G --> T (257 Arg --> Leu), nt 1094 G --> A (365 Arg --> His), and nt 1285 A --> G (429 Lys --> Glu) and they were named G-6-PD San Luis Potosi, G-6-PD Zacatecas, G-6-PD Veracruz, and G-6-PD Yucatán, respectively. To date, a total of 18 different G-6-PD variants have been observed in Mexico and several of them are common in Africa, South Europe, and Southeast Asia.

βA globin gene haplotypes in Mexican Huichols: Genetic relatedness to other populations

The haplotypes of 97 βA independent chromosomes from a Mexican Huichol Native American group were analyzed. The analysis also included 87 βA chromosomes from a Mexican Mestizo population previously studied. Among Huichols, eight different 5′ β haplotypes (5Hps) were observed, with types 1(+ − − − −), 13(+ + + − +) and 2(− + + − +) at frequencies of 0.794, 0.093, and 0.041, respectively. In Mestizos, 17 5Hps were found, types 1, 3(− + − + +), 2, 5(− + − − +) and 9(− − − − −) being the most common at frequencies of 0.391, 0.172, 0.092, 0.069, and 0.046, respectively. 3′ haplotype (3Hps) frequency distributions were 0.443(+ +), 0.083(+ −), and 0.474(− +) in Huichols and 0.563(+ +), 0.149(+ −), and 0.287(− +) in Mestizos. Pairwise comparison for both haplotype distributions between the two populations showed significant differences. Pairwise distributions of 3Hps for Huichols were compared with nine worldwide populations, three African, two Asian, two Melanesian, one Caucasian, and one United States Native American. The distributions of the Huichol were different (P < 0.05) from all populations except the Native American. Neis genetic distances showed the Huichols to be closer to the Native Americans, followed by Melanesians from Vanuatu and Asians; Africans were the farthest. The 5Hp distributions in Mexicans were also compared with 23 worldwide populations (including African, Native American, Asian, Caucasian, and Pacific Islanders). Huichol distributions were different (P < 0.05) from all other populations except Koreans. The Mestizo distribution was also different from the others, except three Caucasian groups. Neis genetic distance between the same populations disclosed that the Huichols are in relatively close proximity to five out of six Asian populations considered. The same analysis with grouped worldwide populations showed Native Americans as population closest to the Huichols, followed by Pacific Islanders and Asians. Present observations are consistent with an important Asian contribution to the Huichol genome in this chromosomal region. Am. J. Hum. Biol. 12:201–206, 2000.

Genetic variation of the FMR1 gene among four Mexican populations: Mestizo, Huichol, Purepecha, and Tarahumara.

Fragile X syndrome is the most common cause of inherited mental retardation; it is caused by expansion of CGG repeats in the first exon of the FMR1 gene. The number of CGG repeats varies between 6 and 50 triplets in normal individuals; the most common alleles have 29 or 30 repeats. Allelic patterns in the global populations are similar; however; some reports show statistical differences among several populations. In Mexico, except by a single report on a western Mestizo population, the allelic frequencies of the FMR1 gene are unknown. In this study, we analyze 207, 140, 138, and 40 chromosomes from Mestizos, Tarahumaras, Huichols, and Purepechas respectively. After PCR amplification on DNA modified by sodium bisulfite treatment, molecular analysis of the FMR1 gene showed 30 different alleles among the 525 chromosomes evaluated. Trinucleotide repeat number in the different Mexican populations varied from 15 to 87, with modal numbers of 32 and 30 in Mestizos and Tarahumaras, 29 and 32 in Purepechas and 30 among Huichols. Together, these allelic patterns differ significantly from those reported for Caucasian, Chinese, African, Indonesian, Brazilian, and Chilean populations. The increased number of the unusual allele of 32 repeats observed in the Mexican mestizo population can be explained from its frequency in at least two Mexican native populations. Am. J. Hum. Biol., 2008.

ALPHA-1,4-GLUCOSIDASE ACTIVITY AND THE PRESENCE OF GERMINAL EPITHELIUM CELLS IN THE SEMEN FOR DIFFERENTIAL DIAGNOSIS OF OBSTRUCTIVE AND NONOBSTRUCTIVE AZOOSPERMIA

Among azoospermics, the activity of seminal alpha-glucosidase (alpha G) is low in obstruction (OBS) cases, but there is no agreement regarding its value in others. With the hypothesis that a more marked decrease in alpha G activity occurs in OBS than in spermatogenesis arrest (SA), the enzyme was measured in the following groups: (1) vasectomized males (n = 15), (2) azoospermics with OBS (n = 7), (3) azoospermics with SA (n = 11), and (4) fertile males (n = 15). Patients within groups 2 and 3 had a testicular volume > or = 15 mL, no clinical evidence of abnormal epididymis, normal serum gonadotropins, and histological diagnosis. alpha G activities (mU/g protein, means +/- SD) by group were (1) 131 +/- 60, (2) 312 +/- 186, (3) 728 +/- 303, and (4) 1176 +/- 374. All between-group differences were significant (t test, p < .01), except for groups 1 vs. 2 comparison (.05 > p > .01). These results support the notion that SA is associated with a decrease in alpha G that is less marked that seen in OBS. The search for germinal epithelium cells in semen also allows discrimination between these two azoospermic groups.

Distribution of three SNPs related to low bone mineral density in Amerindian groups and Mestizos from Mexico.

Some Single nucleotide polymorphisms (SNPs) of several candidate genes have been associated with low bone mineral density (BMD) and fracture risk. As the genetic variability of such SNPs in Hispanic and Native American populations is scarce, we analyzed the three SNPs that have been related with bone mass disorders (Sp1, A163G, and BsmI) located in the genes of Type I Collagen (COL1A1), Osteoprotegerin (OPG), and Vitamin D receptor (VDR) in Mexican Mestizos (people resulting from post‐Columbian admixture) and five Amerindian populations.