Fernando Rivas

Estimation of nonpaternity in the Mexican population of Nuevo Leon: a validation study with blood group markers.

A method for estimating the general rate of nonpaternity in a population was validated using phenotype data on seven blood groups (A1A2BO, MNSs, Rh, Duffy, Lutheran, Kidd, and P) on 396 mother, child, and legal father trios from Nuevo León, Mexico. In all, 32 legal fathers were excluded as the possible father based on genetic exclusions at one or more loci (combined average exclusion probability of 0.694 for specific mother-child phenotype pairs). The maximum likelihood estimate of the general nonpaternity rate in the population was 0.118 +/- 0.020. The nonpaternity rates in Nuevo León were also seen to be inversely related with the socioeconomic status of the families, i.e., the highest in the low and the lowest in the high socioeconomic class. We further argue that with the moderately low (69.4%) power of exclusion for these seven blood group systems, the traditional critical values of paternity index (PI > or = 19) were not good indicators of true paternity, since a considerable fraction (307/364) of nonexcluded legal fathers had a paternity index below 19 based on the seven markers. Implications of these results in the context of genetic-epidemiological studies as well as for detection of true fathers for child-support adjudications are discussed, implying the need to employ a battery of genetic markers (possibly DNA-based tests) that yield a higher power of exclusion. We conclude that even though DNA markers are more informative, the probabilistic approach developed here would still be needed to estimate the true rate of nonpaternity in a population or to evaluate the precision of detecting true fathers.

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.

Poland-Moebius syndrome in a boy and Poland syndrome in his mother.

A 4 4/12‐year‐old boy with the Poland‐Moebius syndrome, whose mother had the Poland syndrome, is presented. This is the first report of the occurrence of both syndromes in the same family, suggesting that they are expressions of the same autosomal dominant gene.

Oral‐facial‐digital syndrome with fibular aplasia: a new variant

Figuera LE, Rivas F, Cantú JM. Oral‐facial‐digital syndrome with fibular aplasia: a new variant.

Allele frequency distributions of six amp-FLPS (D1S80, APO-B, VWA, TH01, CSF1PO and HPRTB) in a Mexican population

Six amplified fragment length polymorphisms or Amp-FLPs, two VNTRs (D1S80 and APO-B) and four STRs (VWA, TH01, CSF1PO and HPRTB), were typed in a Mexican population of the Jalisco state by means of non-denaturing polyacrylamide gel electrophoresis (native PAGE) in standard gel units and silver staining. Genotype distribution was in agreement with Hardy-Weinberg expectations (HWE) for all six markers. Heterozygosity ranged from 70.6 to 83.5%, the cumulated chance of exclusion (CE) and power of discrimination (PD) were 99.4 and 99.99%, respectively. STRs and D1S80 allele frequency distributions (AFD) were similar (P > 0.05) to U.S. Hispanics, but different to U.S. Caucasians and African-Americans. APO-B exhibited similarities with White Brazilians, Spaniards, but differences (P < 0.05) with Amerindian and Black Brazilians.

The phenotype in partial 13q trisomies, apropos of a familial (13;15)(q22;q26) translocation

SummaryA 12 month-old male patient with a karyotype 46, XY,-15,+der(15),t(13;15)(q22;q26)pat is presented. His stillborn sib showed malformations compatible with the 13q deletion syndrome, probably due to a 46,XY, der(13) karyotype. Phenotypic analysis of 41 cases from the literature with partial distal 13q (D13q) trisomies indicate that the segment 13q22 → qter in trisomy with or without another concomitant aneusomy is sufficient to produce the majority of the trisomy 13 syndrome features, some of which (cleft palate, increased HbF and projections in PMN) are present in different non-overlapping partial 13q trisomies. About 82% of the D13q trisomies are inherited, more frequently from the mother.

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

Influence of cytokine and intercellular adhesion molecule-1 gene polymorphisms on acute rejection in pediatric renal transplantation

Abstract:  Immune response regulation by cytokines is a key to understanding AGR. The influence of the functional polymorphisms in genes coding for TNF‐α (−308G > A), IL‐10 (−819C > T, and −1082A > G), IFN‐γ [(CA)n], TGF‐β1 (+869T > C), and iCAM‐1 (R241G and E469K), in addition to HLA and gender matching on the presentation of AGR in 51 pediatric renal recipients during a 36‐month post‐transplantation follow‐up were analyzed. Also, donors and a control group were genotyped. All groups were within Hardy‐Weinberg equilibrium for all polymorphisms except IL‐10–819C > T and TNF‐α (p < 0.005 and p < 0.01, respectively) in recipients. Transplants with gender mismatch showed a higher risk for AGR than those between individuals with gender match (OR, 4.227; p = 0.010). Recipients with a high‐production compared with low‐production TNF‐α allele experienced earlier AGR (p = 0.030), and those with high‐production alleles of both TNF‐α and IFN‐γ showed a further increased risk (OR = 11.129, p = 0.024). These findings support the notion that a single genotype cannot by itself explain an event as complex as AGR. The sum or combination of different specific alleles of these genes could better account for the immune response to an allograft.

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.