Norma Olivares

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.

Genetic polymorphisms of the renin-angiotensin system in preterm delivery and premature rupture of membranes

Introduction. Premature rupture of membranes (PRM) is a late pregnancy complication commonly associated with preterm delivery (PD).Although several markers related to the renin-angiotensin system (RAS) have been evaluated in certain pregnancy complications, only the angiotensin-converting enzyme (ACE) I/D variant has been studied in PD-PRM.The aim of this survey was to investigate the association of the polymorphisms (angiotensin II type 1 [AT1] receptor T174M and M235T, renin G2805A,ACE I/D and AT1-receptor A1166C) of the genes of RAS in women with PD-PRM. Design. Deoxyribonucleic acid samples from 89 Mexican Mestizo women with PD and PRM and 224—288 controls were studied. Polymorphisms were analysed by polymerase chain reaction-sequence specific primer assays. restricted fragment length polymorphism or sequence specific prim assays. Results. For all loci , genotype distribution was in agreement with Hardy—Weinberg expectations in the control group. Significant intergroup difference (case vs. control) was seen for angiotensinogen (AGT) M235T polymorphism, with an increased allele M235 in affected cases (50% vs. 40% in controls).Analysis of two-locus haplotype agrees with an independent segregation of physically unlinked genes. Haplotype AGT 174T-235M was also increased (50 % vs. 40% in controls). Conclusions. Physically unlinked genes involved in RAS segregate independently. The AGT 174—235 region is associated with PD-PRM in this population.

DEFICIENT CELL IMMUNITY AND MILD INTERMITTENT HYPERAMINOACIDEMIA IN A PATIENT WITH THE RUBINSTEIN‐TAYBI SYNDROME

Abstract. Rivas, F., Fragoso, R., Ramos‐Zepeda, R., Vaca, G., Hernandez, A., González‐Quiroga, G., Olivares, Norma and Cantu, J. M. (Divisions of Genetics and Hematology, and Experimental Pathology, Subjefatura de Investigacion Cientifica, Unidad de Investigación Biomédica, Centro Médico de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México). Deficient cell immunity and mild intermittent hyperaminoacidemia in a patient with the Rubinstein‐Taybi syndrome. Acta Paediatr Scand, 69: 123, 1980.—A boy aged 2 years 8 months presenting the Rubinstein‐Taybi Syndrome (RTS) and a history of recurrent gastrointestinal and respiratory infections was studied. Partial deficient cell immunity and intermittent hyperaminoacidemia and aminoaciduria were ascertained. These findings were interpreted as evidence of phenotypic and probably genetic heterogeneity of RTS

Reproductive History in Mothers of Children with Neural Tube Defects

The reproductive history of 100 women with at least 1 child with a neural tube defect (NTD) has been studied. The data analyzed correspond to the period previous to their first visit to a genetic counseling service. A total of 204 pregnancies resulted in 205 outcomes. Of the 100 sibships, 14 (14%) had more than 1 affected member. The pregnancy was shorter than 28 weeks in 56/205 (27%) of the total outcomes. Of 104 evaluable previous outcomes, 34 corresponded to short pregnancies, positioned before an affected (23/60, 38%), a healthy (2/18, 11%), or an undiagnosed product (9/26, 35%). Short pregnancies subsequent to affected outcomes were also increased. The inter-gestational interval varied according to diagnosis: it was longer in the affected group than in the healthy one (0.1 > p > 0.05) and the subsequent intervals were shorter for the affected group (p < 0.05). An increased number of abortions adjacent to affected offspring and a changing fertility pattern, depending on the product diagnosis, point to an environmental etiological component in this high-risk NTD group of mothers.

Worldwide genetic diversity at the HLA-DQA1 locus

Genotype, gene, or phenotype frequency data, obtained by PCR analysis with sequence specific oligonucleotide probes at the HLA‐DQA1 locus, in 176 population samples, each consisting of 30 or more individuals, from all around the world were analyzed. The sampled populations were assigned to the following nine groups: African, Afro‐American, American Native, American Mestizo, Asian, American Caucasian, European Caucasian, Caucasian from other regions, and Pacific Islanders. Observed genotype proportions agreed with Hardy‐Weinberg expectations (HWE) in 90 of the 102 populations for which genotype data are available. The 12 discordant population samples were of substantial mixed origin. For these discordant populations, 41 of the 252 (population by genotype) data points showed significant departures of the observed frequencies in comparison to their HWE predictions. The deviations, by and large (38 of the 41), were in the direction of HWE over‐estimating the actual genotype frequencies. Total heterozygosity (HT) at a worldwide level was 79%, and varied from 56% in American Natives to >80% in Caucasians. Of the total diversity, 94.4% was due to intra‐population and 5.6% to inter‐population variation (FST), partitioned into 3.0% inter‐population within groups and 2.6% inter‐group variation. FST for the locus was high among Africans and American Natives (>9%) and low in Afro‐Americans and American Caucasians (<0.5%). The range for allele specific FST was 0.2% to 5.9%, and the lowest value did not correspond to the same allele in all nine groups. A variance component analysis of allele frequencies showed no relationship of the ratio of between/within group variation with the world average frequency of the respective alleles. The first three principal components explained 36.2%, 27.5%, and 22.9% of the total allelic diversity, respectively. For Caucasian and Afro‐American samples, the first two PCs formed clusters by groups. In contrast, the American Native, Asian, and Pacific Islander groups showed a greater inter‐population diversity, while the corresponding principal component scores of the American Mestizo samples were between American Natives and Caucasians. In aggregate, the analyses indicate that genetic drift in contrast to natural selection, more readily explains the pattern of worldwide diversity at the HLA‐DQA1 locus. Am. J. Hum. Biol. 9:735–749, 1997.

Population data and mutation rate of nine Y-STRs in a mestizo Mexican population from Guadalajara, Jalisco, México

Nine Y-STR (DYS19, DYS390, DYS391, DYS392, DYS446, DYS447, DYS448, DYS456 and DYS458) were analyzed in a male sample of 285 unrelated individuals from Guadalajara, Jalisco, México. The haplotype diversity (0.996) and discrimination capacity (0.986) were calculated. A family study of around 200 father/son pairs and among 1828 meiosis showed five mutational events. All mutations were single step. The overall mutation rate estimated across the nine Y-STRs was 2.7 x 10(-3) (95% CI 1.2-6.4 x 10(-3))/locus/meiosis. The results indicate that these nine loci are useful Y-linked markers for forensic applications.