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La reciente cartografía a escala 1:50.000 de los sectores centrales y meridionales, más desconocidos, de la Sierra de Neiba ha permitido establecer con mayor precisión su estratigrafía. Los materiales más antiguos corresponden a la Unidad de El Manguito, del Cretácico Superior. Son calizas y lutitas pizarrosas con intercalaciones de basaltos que afloran como un fragmento o bloque tectónico de interpretación estructural dudosa en el núcleo de un anticlinal. Por su edad, se considera que esta unidad debe constituir el sustrato de las series paleógenas de la Sierra de Neiba; la composición geoquímica de los basaltos (OIB-basaltos alcalinos intraplaca) sugiere su correlación con la meseta oceánica del Caribe. El registro estratigráfico más o menos continuo comienza en el Eoceno Inferior con el desarrollo de una extensa plataforma carbonatada, relativamente uniforme, que fue el medio de depósito de la Fm Neiba (sensu lato) y sus equivalentes, hasta el Mioceno Inferior. Durante buena parte del Eoceno, estos depósitos carbonatados coexistieron o fueron sustituidos por materiales volcánicos de signatura toleítica a alcalina (OIT a OIA) que se agrupan bajo la nueva denominación de Complejo Volcanosedimentario de El Aguacate de Neiba y se interpretan como generados en un contexto de intraplaca asociados al desarrollo de una pluma mantélica. La sedimentación de la Fm Sombrerito durante el Mioceno muestra los primeros signos de inestabilidad en la región: mientras que en los sectores septentrionales y centrales de la sierra sus facies más típicas se depositan en una cuenca turbidítica, en su extremo suroccidental afloran las calizas arrecifales de su Mb Barahona, propias de ambientes de plataforma somera, que se extienden con gran uniformidad hacia el sur hasta los dominios de la Sierra de Bahoruco. La Unidad de Cortadero, de nueva denominación y equivalente en edad a la Fm Sombrerito, con una posición intermedia entre ambos tipos de facies, puede representar el tránsito entre ellas.

The marker association segregation chi-square (MASC) method was applied to a sample of 416 Caucasians affected with insulin-dependent diabetes mellitus (IDDM), for which information on the parental and sibship status was available, as well as HLA typing. We show that the model which best explains all the observations assumes a cis or trans complementation of two tightly linked genes within the HLA region, an additional maternal effect, and other familial factors. The HLA molecule corresponding to the complementation of Arg52(+) and Asp57(-) has been recently proposed as explaining susceptibility to IDDM. However, this hypothesis does not account for the overall observations made on the HLA marker in IDDM patients and their relatives. The MASC method may also be applied to evaluate the risk for relatives of an affected individual (the "index"). For example, the risk for a sib depends not only on the parental status and on the number of HLA haplotypes he shares with the index, but also on which haplotype the index himself inherited from his mother and father.

Among 285 caucasoid families genotyped for HLA-A, B, C, DR including at least one insulin-dependent diabetic child, we have studied the effect of the DR3 and DR4 antigens inherited from the father or the mother (DR3p, DR3m, DR4p and DR4m, respectively) on the recurrence of the disease among siblings; families with affected parents being excluded, a total of 37 affected and 200 non affected siblings have been taken into consideration. Among the DR3, DR4 positive siblings, the DR4p/DR3m genotype was observed at a greater frequency than the DR3p/DR4m genotype among affected, but not among unaffected siblings. Comparing the respective frequencies between affected and unaffected siblings, the relative risk was 8.1 (p less than 10(-6) among DR4p/DR3m positive siblings, but is was not significantly increased among DR3p/DR4m positive siblings. The excess of maternal DR3 among affected siblings of diabetic children could be due to a gestational event associated with HLA-DR3, e.g. education of the fetal immune repertoire or the transmission of a viral infection by the mother to the fetus during pregnancy, after reactivation of the latent viral disease.

Linkage studies have led to the identification of several chromosome regions that may contain susceptibility loci to type I diabetes (IDDM), in addition to the HLA and INS loci. These include two on chromosome 6q, denoted IDDM5 and IDDM8, that are not linked to HLA. In a previous study, we noticed that the evidence for linkage to IDDM susceptibility around the HLA locus extended over a total distance of 100 cM, which suggested to us that another susceptibility locus could reside near HLA. We developed a statistical method to test this hypothesis in a panel of 523 multiplex families from France, the United States, and Denmark (a total of 667 affected sib pairs, 536 with both parents genotyped), and here present evidence (P = .00003) of a susceptibility locus for IDDM located 32 cM from HLA in males but not linked to HLA in females and distinct from IDDM5 and IDDM8. A new statistical method to test for the presence of a second susceptibility locus linked to a known first susceptibility locus (here HLA) is presented. In addition, we analyzed our current family panel with markers for IDDM5 and IDDM8 on chromosome 6 and found suggestions of linkage for both of these loci (P = .002 and .004, respectively, on the complete family panel). When cumulated with previously published results, with overlapping families removed, the affected-sib-pair tests had a significance of P = .0001 for IDDM5 and P = .00004 for IDDM8.

Among patients with insulin-dependent diabetes mellitus (IDDM), an excess of DR3 and DR4 alleles is classically described when compared with the general population. In addition, an excess of maternal DR3 and paternal DR4 alleles among patients (DR3DR4) is observed. In order to explain these observations, two alternative hypotheses can be tested: maternal effect and parental imprinting. Maternal effect has been tested and not rejected on a sample of 416 caucasians affected with IDDM. Under this hypothesis, the children of a DR3 mother are expected to have an earlier exposure and, hence, an earlier age at onset. However, we did not observe such a difference in age at onset in this data set. Using the marker-association-segregation-chi 2 method, we have tested four hypotheses with different parental effects of two susceptibility alleles, alpha 0 and beta 0, at two different closely linked loci. Under the hypothesis that best fitted the data, the probability of being affected depended on the parental inheritance of the susceptibility alleles, suggesting parental imprinting (i.e., differential role of maternal and paternal allele), without evidence for a cis-trans effect. We conclude that parental imprinting on a specific allelic combination may explain the observations on the HLA genotypes of the patients and their relatives.

It is now well established that HLA system is involved in the susceptibility to Type 1 diabetes mellitus. In this study we look for a possible effect of the Gm system. A first study (cases-controls) suggests that among individuals who had HLA-DR3 but not HLA-DR4 or HLA-DR4 without HLA-DR3, there is a possible effect of the phenotype Gm3,23,5 or Gm3,-5 in the susceptibility to IDDM. Moreover, we have tested by the sibpair method whether HLA and Gm are transmitted independently from IDDM: an unaffected sib, sharing the same HLA haplotypes than an affected individual, seems to be more often phenotypically different at the Gm loci.

In normal subject, during a continuous infusion of gluoose (1.15 mmol/min. m2) and insulin (42 mU/min, m2), the endogenous insulin secretion is inhibited ; the mean steady state plasma glucose (SSPG) and insulin (SSPI) levels are achieved after 90 min. The SSPG is of 6.6 mM, It was generally accepted that the SSPG reflects individual insulin sensitivity. 18 children withou acidosis starting a diabetes mellitus received such an infusion during 4 hours. Under these conditions SSPG, SSPI and SSPFFA levels are achieved after 120 or 180 min. SSPG level varies from 4.4. to 17.8 mM. SSPI level is of 45 ± 8 uU/ml. There is no relationship between the SSPG level and SSPI, SSPFFA and acetonuria, between the SSPG level and the baseline value of cortisol, glucagon, alanine, as well as the highest level of C. peptide. The rate of FFA decreases similarly, whatever rate achieved at the SSPG. However there is a correlation (p < 0.01) between the SSPG level and the FFA and the triglyceride levels at baseline. These results show that in diabetic children without acidosis, there is a great variability of the insulin sensitivity. The initial levels of the triglycerides and of the FFA are closely correlated to this sensitivity.