Pattern of mutation rates in the germline of Drosophila melanogaster males from a large-scale mutation screening experiment.

The sperm or eggs of sexual organisms go through a series of cell divisions from the fertilized egg; mutations can occur at each division. Mutations in the lineage of cells leading to the sperm or eggs are of particular importance because many such mutations may be shared by somatic tissues and also may be inherited, thus having a lasting consequence. For decades, little has been known about the pattern of the mutation rates along the germline development. Recently it was shown from a small portion of data that resulted from a large-scale mutation screening experiment that the rates of recessive lethal or nearly lethal mutations differ dramatically during the germline development of Drosophila melanogaster males. In this paper the full data set from the experiment and its analysis are reported by taking advantage of a recent methodologic advance. By analyzing the mutation patterns with different levels of recessive lethality, earlier published conclusions based on partial data are found to remain valid. Furthermore, it is found that for most nearly lethal mutations, the mutation rate at the first cell division is even greater than previous thought compared with those at other divisions. There is also some evidence that the mutation rate at the second division decreases rapidly but is still appreciably greater than those for the rest of the cleavage stage. The mutation rate at spermatogenesis is greater than late cleavage and stem-cell stages, but there is no evidence that rates are different among the five cell divisions of the spermatogenesis. We also found that a modestly biased sampling, leading to slightly more primordial germ cells after the eighth division than those reported in the literature, provides the best fit to the data. These findings provide conceptual and numerical basis for exploring the consequences of differential mutation rates during individual development.

Highly variable recessive lethal or nearly lethal mutation rates during germ-line development of male Drosophila melanogaster.

Each cell of higher organism adults is derived from a fertilized egg through a series of divisions, during which mutations can occur. Both the rate and timing of mutations can have profound impacts on both the individual and the population, because mutations that occur at early cell divisions will affect more tissues and are more likely to be transferred to the next generation. Using large-scale multigeneration screening experiments for recessive lethal or nearly lethal mutations of Drosophila melanogaster and recently developed statistical analysis, we show for male D. melanogaster that (i) mutation rates (for recessive lethal or nearly lethal) are highly variable during germ cell development; (ii) first cell cleavage has the highest mutation rate, which drops substantially in the second cleavage or the next few cleavages; (iii) the intermediate stages, after a few cleavages to right before spermatogenesis, have at least an order of magnitude smaller mutation rate; and (iv) spermatogenesis also harbors a fairly high mutation rate. Because germ-line lineage shares some (early) cell divisions with somatic cell lineage, the first conclusion is readily extended to a somatic cell lineage. It is conceivable that the first conclusion is true for most (if not all) higher organisms, whereas the other three conclusions are widely applicable, although the extent may differ from species to species. Therefore, conclusions or analyses that are based on equal mutation rates during development should be taken with caution. Furthermore, the statistical approach developed can be adopted for studying other organisms, including the human germ-line or somatic mutational patterns.

p53 codon 72 polymorphism and risk of cervical cancer.

Storey et al. (1998) implicated the proline/argine polymorphism of the codon 72 of the tumor-suppressor gene p53 in the development of cervical cancer (CC) with the observation that the p53 protein is more efficiently inactivated by the E6 oncoprotein of human papillomavirus in p53 arginine as compared with its proline isoform. These authors further noted that in the United Kingdom, individuals homozygous for the arginine allele were several times more susceptible to HPV-associated tumorigenesis that proline/arginine heterozygotes. Subsequent studies in different countries failed to unanimously confirm this association. Motivated by the high incidence of CC in Chile, we undertook a case control study obtaining the following frequencies for genotypes PP, AP and AA in 60 ICC cases and 53 carefully selected controls: 0.067, 0.250, 0.683 and 0.075, 0.453, 0.472 respectively. A significant difference (X2 = 3.19 p < 0.02) and an odds ratio of 2.62 supported Storey et al (1998)'s results. In addition, rejecting previous hypotheses about the world distribution of the p53 codon 72 polymorphism, we conclude that this distribution most likely represents ancient human dispersal routes. Several methodological and biological explanations for the results obtained in previous negative association studies are briefly discussed.

P53 Codon 72 polymorphism and risk of cervical cancer

Storey et al. (1998) implicated the proline/argine polymorphism of the codon 72 of the tumor-suppressor gene p53 in the development of cervical cancer (CC) with the observation that the p53 protein is more efficiently inactivated by the E6 oncoprotein of human papillomavirus in p53 arginine as compared with its proline isoform. These authors further noted that in the United Kingdom, individuals homozygous for the arginine allele were several times more susceptible to HPV-associated tumorigenesis that proline/arginine heterozygotes. Subsequent studies in different countries failed to unanimously confirm this association. Motivated by the high incidence of CC in Chile, we undertook a case control study obtaining the following frequencies for genotypes PP, AP and AA in 60 ICC cases and 53 carefully selected controls: 0.067, 0.250, 0.683 and 0.075, 0.453, 0.472 respectively. A significant difference (X2 = 3.19 p < 0.02) and an odds ratio of 2.62 supported Storey et al (1998)'s results. In addition, rejecting previous hypotheses about the world distribution of the p53 codon 72 polymorphism, we conclude that this distribution most likely represents ancient human dispersal routes. Several methodological and biological explanations for the results obtained in previous negative association studies are briefly discussed

Admixture in Hispanics: distribution of ancestral population contributions in the Continental United States.

The effect of gene flow on Hispanic populations from different geographic regions of the United States was analyzed using six autosomal DNA markers (LDLR, GYPA, HBGG, D7S8, GC, and HLA-DQA). By region of sampling, the Hispanic populations showed different ancestry contributions, from a trihybrid structure with European, Native American, and African contributions (California, Nevada, Florida, New Jersey, and Virginia) to a dihybrid structure with European and American contributions (Southwest population) or European and African contributions (Pennsylvania and Southeast population). These findings allowed us to define two regional groups, the West and the East. In the former, Native American contributions ranged from 35.58% to 57.87%; in the East region the values ranged from 0% to 21.27%. An African influence was similar in both regions, ranging from 0% to 17.11%, with a tendency of increasing in the East region. These data reflect the different origins of the Hispanic populations that led to the present ones. In the West, Hispanics are mostly of Mexican origin, and in the East, they are predominantly of Cuban and Puerto Rican origin.

Measuring health beliefs in Spanish-speaking Mexican Americans with type 2 diabetes: adapting an existing instrument.

Mexican Americans bear a disproportionate burden of type 2 diabetes, and although clinicians and researchers are beginning to develop culturally competent interventions, few instruments are available for measuring variables relevant to health outcomes. The purpose of this study was to determine the psychometric properties of a diabetes-related health belief instrument translated for use with Spanish-speaking Mexican Americans. Three hundred and twenty-six Spanish-speaking Mexican Americans from Starr County, a Texas-Mexico border community, diagnosed with type 2 diabetes participated in the study. Factor analysis was used to examine the factor structure of the instrument, and reliability testing was conducted to determine the internal consistency of the resulting factors. The final instrument had 25 items with four subscales-Barriers, Social Support for Diet, Impact of Job on Therapy, and Benefits of Therapy-and one item to measure, Control. Internal consistency coefficients for these subscales were .56, .62, .86, and .90, respectively. The translated instrument needs to be tested over time with other Hispanic populations.

Genetic admixture in three Mexican Mestizo populations based on D1S80 and HLA-DQA1 loci.

This study compares genetic polymorphisms at the D1S80 and HLA-DQA1 loci in three Mexican Mestizo populations from three large states (Nuevo León, Jalisco, and the Federal District). Allele frequency distributions are relatively homogenous in the three samples; only the Federal District population shows minor differences of the HLA-DQA1 allele frequencies compared with the other two. In terms of genetic composition, these Mestizo populations show evidence of admixture with predominantly Spanish-European (50-60%) and Amerindian (37-49%) contributions; the African contribution (1-3%) is minor. Together with the observation that in Nuevo León, the admixture estimates based on D1S80 and HLA-DQA1, are virtually the same as those reported earlier from blood group loci, suggests that DNA markers, such as D1S80 and HLA-DQA1 are useful for examining genetic homogeneity/heterogeneity across Mestizo populations of Mexico. The inverse relationship of the proportion of gene diversity due to population differences (Gst) to within population gene diversity (Hs) is also consistent with theoretical predictions, supporting the use of these markers for population genetics studies.

Facial clefting and Amerindian admixture in populations of Santiago, Chile.

Among congenital malformations, cleft lip with and/or without cleft palate has the highest relative frequencies and shows ethnic variation in prevalence. Both malformations are generally more common among the Asian than European populations. Many populations of Chile have genes of Amerindian and Spanish ancestry, with considerable variation in the degree of Amerindian admixture. Therefore, the association of clefting incidence with Amerindian admixture was investigated. The frequency of cleft lip and/or cleft palate in infants born in three private and two public maternity service clinics of Santiago, Chile, is reported. The private clinic patients have a higher socioeconomic status (SES) than those receiving the public services. They also differ in estimated Amerindian admixture. More than 200,900 consecutive birth records were reviewed. The rate of clefting malformations is 15.3 per 10,000 live births. Based on allele frequencies at the ABO and Rh blood group loci, the percentage of Amerindian admixture is higher in infants born in the public compared to those born in the private maternity service clinics. Amerindian admixture is positively correlated (Spearman's p = 0.9, P = 0.008) with clefting rate across these samples. Clefting is also associated with SES, with lower SES showing higher clefting rates. Mothers of clefting newborns also have higher estimated Amerindian admixture compared to those of normal newborns. The results support the view that in Chilean populations, susceptibility to clefting is related to Amerindian ancestry. Am. J. Hum. Biol. 9:225-232, 1997. © 1997 Wiley-Liss, Inc.

Blood lead concentrations and associated factors in residents of Monterrey, México

Data from interviews of 469 random subjects living in Monterrey, Nuevo Leon, Mexico were analyzed to investigate factors associated with blood lead (PbB)- The following criteria were considered: age, sex, residence zone, occupation, smoking, alcohol consumption, and the use of glazed pottery. Multiple linear regression analysis disclosed that PbB concentration was significantly higher in males, in residents of northeastern (NE) Monterrey, an in blue-collar workers. The highest atmospheric lead (PbA) concentrations of all Monterrey were also found in the NE, the zone that contains the greatest density of factories within the city. PbB and PbA means were significantly correlated (r=0.964) with regards to the four urban zones considered. It is concluded that increased PbB level in specific categories is probably explained by exposure to PbA originating from industrial emissions

Genetic variation by birth cohorts in Mexican Americans of Starr County, Texas.

Mexican Americans residing in Starr County, Texas, were grouped by their year of birth (1896-1925, 1926-1955, and 1956-1985) to determine the extent of birth cohort-related genetic variation within this population and the genetic differences, if any, from the Mexican population residing in the Metropolitan Monterrey Area (MMA), Nuevo León, México. Twenty-one genetic markers were analyzed which indicate that the three birth cohort groups are genetically indistinguishable. Gene diversity analysis suggests that more than 99.8% of the total gene diversity can be attributed to variation between individuals within the birth cohort populations and that the subdivision by birth cohort has only a small contribution (0.18%) to the total gene diversity. Genetic admixture analysis indicates a predominant influence from the Spanish, and that the three birth cohort groups were similar in terms of contributions of this ancestral population. The genetic structure of the Mexican American population of Starr County was also similar to the Mexican population from the State of Nuevo León, México. These findings, together with previous results, suggest that the Mexican Americans of Starr County, Texas, classified by gender, birthplace, and age, are not genetically distinguishable and are similar to the Mexican populations of the State of Nuevo León. © 1994 Wiley-Liss, Inc.

Obesity and upper body fat distribution in Mexican American children from families with a diabetic proband.

Upper and centralized body fat distribution is associated with non-insulin dependent diabetes mellitus (NIDDM). Few studies have focused on anthropometric characteristics of preadults from families in which there is a diabetic (NIDDM) proband. This study explores the prevalence of upper and centralized body fatness in Mexican American children from the Diabetes Alert study (1981-1983) in Starr County, Texas. Anthropometric data on 165 males and 224 females 9-19 years include measures of adiposity such as skinfold thicknesses and the body mass index (BMI), a measure of overweight. They show rates of obesity two to three times that of White children of comparable age and sex from National Health Surveys. In comparison with U.S. White subjects, Mexican American adults are shorter, have more adiposity and arm muscle mass and have sitting heights and body breadths at the mean of these dimensions for the U.S. POPULATION: Children from Diabetes Alert families show only marginal excess of severe obesity (> 95th percentile of BMI) when compared to the general population of children surveyed in Starr County schools. Girls from these families, but not boys, have excess fatness in the BMI compared to Mexican American children from the Hispanic Health and Nutrition Examination Survey (HHANES); suprailiac skinfold thicknesses are also greater in children of the Diabetes Alert study than in HHANES children. From 1972 through 1982, Mexican American children in South Texas showed an increase in average stature, weight, and the BMI. These data together suggest that excessive obesity exists and may be increasing in children in populations at risk for NIDDM. The prevention of NIDDM in the Mexican American population may be more effective if educational and promotional interventions include the school aged population. © 1993 Wiley-Liss, Inc.

Los aimarás del oeste de Bolivia: salud y enfermedad / The aymará of Western Bolivia: health and disease

Desde hace tiempo la comunidad médica mundial se ha interesado en las enfermedades y la incapacidad relacionadas con la altitud, entre los habitantes de las ciudades y poblaciones de los Andes. Sin embargo, con muy pocas excepciones, la información sobre este tema ha sido algo limitada. Para remediar esta situación, una serie de instituciones académicas y gubernamentales de Bolivia, Chile, Perú, Ecuador y los Estados Unidos, han aunado sus esfuerzos en un amplio proyecto de investigación, conocido como el Programa Multinacional Andino de Genética y Salud. Como parte de este programa, este artículo comunica los resultados del estudio de 429 personas que viven en dos comunidades de los Andes del oeste de Bolivia (AU)

Los aimarás del oeste de Bolivia: salud y enfermedad / The aymará of Western Bolivia: health and disease

Desde hace tiempo la comunidad médica mundial se ha interesado en las enfermedades y la incapacidad relacionadas con la altitud, entre los habitantes de las ciudades y poblaciones de los Andes. Sin embargo, con muy pocas excepciones, la información sobre este tema ha sido algo limitada. Para remediar esta situación, una serie de instituciones académicas y gubernamentales de Bolivia, Chile, Perú, Ecuador y los Estados Unidos, han aunado sus esfuerzos en un amplio proyecto de investigación, conocido como el Programa Multinacional Andino de Genética y Salud. Como parte de este programa, este artículo comunica los resultados del estudio de 429 personas que viven en dos comunidades de los Andes del oeste de Bolivia (AU)