Different numbers of maternal and paternal siblings of cystic fibrosis patients

Summary When 458 parents of children suffering from cystic fibrosis (CF) from all over the German Democratic Republic were interviewed to determine the number of their siblings, it was found that the maternal families had a total of 1369 children and the paternal, 1220. While the fathers of CF patients tended to originate from families with one or two children, more mothers than fathers came from families with three to twelve children (P=0.01). The average number of children in the maternal families was 2.99; in the paternal families, only 2.66. To rule out any methodological errors, sibs of mothers and fathers of various control groups were studied. We found that the number of siblings in these groups was balanced. The differences in our findings are probably due to CF heterozygosity. The underlying mechanism is unknown.     

Heterozygosity and craniofacial dimensions of Zapotec school children from a subsistence community in the valley of Oaxaca, southern Mexico

Gene flow is associated with differences in craniofacial and postcranial dimensions among indigenous populations of southern Mexico. This study compares four craniofacial dimensions in 322 children from families which have an average inbreeding coefficient of 0.01 and 36 children from families which have an inbreeding coefficient of zero (more heterozygous) in a Zapotec speaking community. In addition, two indices were computed. With sex and chronological age constant, there is a statistically significant difference between more and less heterozygous children in bizygomatic diameter. Differences in biparietal diameter and fronto-occipital length reflect the same tendency. The differences probably reflect more an effect of heterozygosity on these dimensions than facial dissimilarity of the populations from which the new genetic materials were drawn because gene flow was from related groups of Indians (e.g., Mixtec) in southern Mexico. Hence, midface growth and overall normal size appear to be affected by fluctuation in level of heterozygosity.     

Increased risk of death from measles in children with a sibling of opposite sex in Senegal.

OBJECTIVE--To examine whether contracting measles from a sibling of the opposite sex affects mortality. DESIGN--Prospective registration during 15-20 years of all births and deaths, including 243 measles related deaths. Measles infection was not registered; however, as in fatal cases measles was probably contracted from a maternal sibling the risk of dying during measles outbreaks was examined in families with two boys, two girls, or a boy and a girl. SETTING--31 small villages in two rural areas of eastern Senegal. SUBJECTS--766 children living in families with two children aged under 10 years during outbreaks of measles, 107 (14%) of whom died of measles. MAIN OUTCOME MEASURE--Deaths from measles, size of village, age and sex of maternal siblings. RESULTS--The interval between outbreaks in the same village was greater than 10 years. The risk of dying of measles was significantly related to age, increasing with the age difference between siblings and decreasing with the size of village. In a multiple logistic regression analysis adjusting for these background factors, children in families with a boy and a girl had a significantly higher mortality than children in families with two boys or two girls (odds ratio = 1.81, 95% confidence interval 1.17 to 2.82). The increase in risk was the same for boys and girls in families with two children one of whom was a boy and one a girl. CONCLUSION--Cross sexual transmission may be an important determinant of severity of measles infection.     

Analysis of yeast pms1, msh2, and mlh1 mutators points to differences in mismatch correction efficiencies between prokaryotic and eukaryotic cells

Genetic stability relies in part on the efficiency with which post-replicative mismatch repair (MMR) detects and corrects DNA replication errors. In Escherichia coli, endogenous transition mispairs and insertion/deletion (ID) heterologies are corrected with similar efficiencies – but much more efficiently than transversion mispairs – as revealed by mutation rate increases in MMR mutants. To assess the relative efficiencies with which these mismatches are corrected in the yeast Saccharomyces cerevisiae, we examined repair of defined mismatches on heteroduplex plasmids and compared the spectra for >1000 spontaneous SUP4-o mutations arising in isogenic wild-type or MMR-deficient (pms1, mlh1, msh2) strains. Heteroduplexes containing G/T mispairs or ID heterologies were corrected more efficiently than those containing transversion mismatches. However, the rates of single base-pair insertion/deletion were increased much more (82-fold or 34-fold, respectively) on average than the rate of base pair substitutions (4.4-fold), with the rates for total transitions and transversions increasing to similar extents. Thus, the relative efficiencies with which mismatches formed during DNA replication are repaired appear to differ in prokaryotic and eukaryotic cells. In addition, our results indicate that in yeast, and probably other eukaryotes, these efficiencies may not mirror those obtained from an analysis of heteroduplex correction.     

Analysis of yeast pms1, msh2, and mlh1 mutators points to differences in mismatch correction efficiencies between prokaryotic and eukaryotic cells.

Genetic stability relies in part on the efficiency with which post-replicative mismatch repair (MMR) detects and corrects DNA replication errors. In Escherichia coli, endogenous transition mispairs and insertion/deletion (ID) heterologies are corrected with similar efficiencies – but much more efficiently than transversion mispairs – as revealed by mutation rate increases in MMR mutants. To assess the relative efficiencies with which these mismatches are corrected in the yeast Saccharomyces cerevisiae, we examined repair of defined mismatches on heteroduplex plasmids and compared the spectra for >1000 spontaneous SUP4-o mutations arising in isogenic wild-type or MMR-deficient (pms1, mlh1, msh2) strains. Heteroduplexes containing G/T mispairs or ID heterologies were corrected more efficiently than those containing transversion mismatches. However, the rates of single base-pair insertion/deletion were increased much more (82-fold or 34-fold, respectively) on average than the rate of base pair substitutions (4.4-fold), with the rates for total transitions and transversions increasing to similar extents. Thus, the relative efficiencies with which mismatches formed during DNA replication are repaired appear to differ in prokaryotic and eukaryotic cells. In addition, our results indicate that in yeast, and probably other eukaryotes, these efficiencies may not mirror those obtained from an analysis of heteroduplex correction. Received: 15 November 1998 / Accepted: 4 February 1999     

Age and chromosome nondisjunction]

The parental age in 77 families of Down syndrome (DS) children with the known origin of extra chromosome 21 and in 12 families of DS children resulting from de novo translocation (more probable than not in 2 meiotic division) was studied. It was shown that when nondisjunction occurred in the 1st meiotic division, both in oogenesis (n = 30) and spermatogenesis (n = 12), mean parental ages and age distributions were different from that of control (400 couples with normal children). The mean age and age distribution were found to differ from control when nondisjunction occurred in the 2nd meiotic division of oogenesis (n = 19). On the basis of our information and the previously published data, lack of the effect of parental age on chromosome segregation in the Ist meiosis may be inferred. It is chromatid disjunction in the 2nd meiosis which is more probably age-dependent. The reasons preventing elucidation of real associations are under debate.     

Food Choices and Consequences for the Nutritional Status: Insights into Nutrition Transition in an Hospital Community

Introduction

Although economic development is generally accompanied by improvements in the overall nutritional status of the country’s population the ‘nutritional transition’ often involves a shift to high energy diets and less exercise with negative consequences. This pilot study was done to examine if education of parents operates at the household level to influence dietary choices and the nutritional status of children in a small community of hospital workers.

Material and Methods

3 groups of persons with varying skill and education levels participated. Weighed food logs were used in all households to calculate ‘adult equivalent’ per-capita-consumption. Nutrients were calculated using nutrients calculator software. BMI was used to classify children as underweight, normal weight and overweight.

Results

128 individuals participated from 30 families included 47 children. 10 children (21%) were underweight, 29 (62%) were normal and 8 (17%) were overweight. Energy consumption was highest in families with overweight children 2692 +/-502 compared to 2259 +/-359 in families with normal weight and 2031+/-354 in the family of underweight children. These differences were statistically significant. 42% underweight children belonged to Class 1 at the lowest skill level and there were no overweight children in this group. Most of the overweight children belonged to Class 2. In Class 3 there were no underweight children and the majority was normal weight children.

Conclusion

Underweight children came from the poorer households. Per capita intake of the family as a whole correlated well with BMI in the children. There was increased obesity in middle income families belonging to Class 2—probably in families who move up the scale from deprivation. Nutritional status in children correlated mostly with maternal education status.     

Base mismatch-specific endonuclease activity in extracts from Saccharomyces cerevisiae.

An endonuclease activity (called MS-nicking) for all possible base mismatches has been detected in the extracts of yeast, Saccharomyces cerevisiae. DNAs with twelve possible base mismatches at one defined position are cleaved at different efficiencies. DNA fragments with A/G, G/A, T/G, G/T, G/G, or A/A mismatches are nicked with greater efficiencies than C/T, T/C, C/A, and C/C. DNA with an A/C or T/T mismatch is nicked with an intermediate efficiency. The MS-nicking is only on one particular DNA strand, and this strand disparity is not controlled by methylation, strand break, or nature of the mismatch. The nicks have been mapped at 2-3 places at second, third, and fourth phosphodiester bonds 5' to the mispaired base; from the time course study, the fourth phosphodiester bond probably is the primary incision site. This activity may be involved in mismatch repair during genetic recombination.     

Recruitment and attrition in twin register studies of childhood behavior: the example of the Australian Twin ADHD Project.

There are a growing number of large-scale initiatives for twin registers of children. The Australian Twin ADHD Project (ATAP) is used to illustrate two key limitations which may arise with such studies, namely (1) the importance of including or possibly excluding families in which one or both twins have significant developmental disability, and (2) the selective failure to recruit and/or the selective attrition of families in which parents and children share behavioral difficulties. Initially ATAP excluded 1 in 6 of families whose twins were enrolled in the volunteer-based Australian Twin Registry (ATR), and as more children with significant problems were identified, these families were sequentially excluded. With longitudinal data over ten years, two points about retention were identified: the difficulty of retaining the twins in late adolescence, and the loss of the families whose twins had more ADHD symptoms. We discuss strategies for limiting the loss of families and for ensuring comparability of data across registers with similar interests but different methods of recruitment and exclusion.     

Ambivalence toward small families in rural Latin America

Data from a rural fertility survey conducted among 6814 15-49 year old women in Costa Rica. Colombia, Mexico, and Peru in 1968 and 1969 is used to determine social definitions of large and small families and advantages and disadvantages associated with family size. Large families were defined as having between 9.5-10.7 children. Small families were defined as having 3.2-4.0 children. 79% found disadvantages to large families (costs and/or influence of cost factors on family well being) compared to 38% for small families (better care for children and better off economically). More than 1/2 the women preferred small families to large, with less than 10% preferring large families. The mean number of children considered ideal was 4.6-6.3. 35-59% wanted no more children.     

Influence of some socio-economic factors on growth and development of the boys in the Tuzla region (Bosnia and Herzegovina)

The impact of certain exogenous factor (socio-economic, ecological) has been investigated with special attention paid to the parents' living standard, and number of family members on some anthropometric parameters like: body height, body mass, chest circumference, upper leg circumference, upper arm circumference, sitting height, arm length, leg length, pelvis width, shoulders width, lenght of head and with of head on the sample of 698 boys aged 11 to 16 (17) years in the Tuzla region (the northeastern Bosnia, Western Balkan peninsula). Anthropometric measurements have been carried out using methodology proposed by the International Biological program (IBP). The results of these investigations have shown that there is a certain impact of the socio-economic conditions on the growth and development of boys. Children from families that have better living standard are, as a rule, taller, which is indicated by the statistical significant differences (P > 0.01). This trend indicates also value of Body Mass Index (BMI), which is in younger children from the families with lower living standard 16, while in the same category in the children from the families with better living standard it has value 18.5. The real impact of living conditions on the dynamics of development could be the best seen in the period of puberty. The number of children in the family has negative relationship with anthropometric features. Statistically significant differences (P > 0.001) have been detected in numerous analysed features in families with one or two children in comparison with families with three, four, or five children. Therefore, BMI has been significantly lower (16) in children from families with several children, while in the families with one child in the same growth class (11 years) it was significantly higher (17.4). Similar value of BMI (17.9) have children from the families with five children and which are 17 years old. Besides socio-economic conditions, high level of environmental pollution which is typical for Tuzla region for a long time, has also significant impact on the growth and development of children.     

Biased short tract repair of palindromic loop mismatches in mammalian cells.

Mismatch repair of palindromic loops in the presence or absence of single-base mismatches was investigated in wild-type and mismatch-binding defective mutant Chinese hamster ovary cells. Recombination intermediates with a maximum heteroduplex DNA (hDNA) region of 697 bp contained a centrally located, phenotypically silent 12-base palindromic loop mismatch, and/or five single-base mismatches. In wild-type cells, both loops and single-base mismatches were efficiently repaired (80-100%). When no other mismatches were present in hDNA, loops were retained with a 1.6-1.9:1 bias. However, this bias was eliminated when single-base mismatches were present, perhaps because single-base mismatches signal nick-directed repair. In the multiple marker crosses, most repair tracts were long and continuous, with preferential loss of markers in cis to proximal nicks, consistent with nicks directing most repair in this situation. However, approximately 25% of repair tracts were discontinuous as a result of loop-specific repair, or from segregation or short tract repair of single-base mismatches. In mutant cells, single-base mismatches were repaired less frequently, but the loop was still repaired efficiently and with bias toward loop retention, indicating that the defect in these cells does not affect loop-specific repair. Repair tracts in products from mutant cells showed a wide variety of mosaic patterns reflecting short regions of repair and segregation consistent with reduced nick-directed repair. In mutant cells, single-base mismatches were repaired more efficiently in the presence of the loop than in its absence, a likely consequence of corepair initiated at the loop.     

Stress in families of children who have ingested poisons.

One hundred families of children under 5 years admitted to Cardiff Hospitals after accidentally ingesting poisons were compared with 100 control families matched for socioeconomic class and age and sex of the child. Questioning about five major stress factors (serious family illness, pregnancy, recent family moves, one parent away from home, anxiety or depression in one or both parents) disclosed significantly more stress in the affected families than in the controls. Thirty of the affected families had more than one major stress factor compared with four of the controls, while 63 of the controls had no major stress factor compared with 24 of the affected families (P less than 0.001). In only four of the affected families was there no stress factor. Fifteen children took poisons in homes other than their own. Unemployment was significantly more prevalent in the affected families than in the general population, though apart from this the socioeconomic backgrounds were similar. There were significantly more accidents and childhood poisonings in the parents and siblings of affected children than in the control families. In 25% of the cases poisoning was with Angiers Junior Aspirin.     

Segregation distortion in Rh polymorphism

Segregation distortion for the Rh system is reported. Mother-infant pairs (1018 pairs) from maternity service divisions of government hospital and 216 complete families with a total of 692 children, of Visakhapatnam (Andhra Pradesh, South India) were typed for the D-d alleles of Rh system. The segregations analysis made by means of the T matrix method of ITO matrices, assuming Hardy-Weinberg equilibrium, reveals that: Rh-positive mothers produce fewer Rh-negative children with significance and Rh-negative mothers produce more Rh-positive children with less significance than expected in both the mother-child and family studies. This results in a reduction in the d allele from mothers to their children. Known Rh antigenic specificities and reproductive compensation do not explain the observed distortion. Other selectively acting forces probably linked to Rh compatibility system seem to be operating to gain d alleles to maintain Rh polymorphism.     

Genetic demographic study of an urban sample of Turkmen-teke with behavioral abnormalities

Genetic and demographic studies of urban sample of Turkmen-teke (Ashkhabad city) were performed among probands-36 patients with diagnosis of "schizophrenia" and their 840 relatives. Clinical analysis revealed 27.8% of phenocopies. In other 26 families the genealogical analysis showed autosomal-dominant (12 families), probably, autosomal-dominant (9 families) as well as autosomal-recessive (3 families) types of inheritance of pathology, in two families the type being not established. The empiric risk of affection was determined to be 24.2% for parents, 75.5% for sibs and 33.3% for children. Mean number of children per one woman is 3.53, which is significantly lower than mean populational number (6.17). High level of endogamy of the urban sample tested is established, the total coefficient of inbreeding being 0.009856; grandparents of the probands appeared to be exclusively of rural origin. The negative action of selection (decreased fitness), preferentially monogenic type of heredity and high level of endogamy are discussed as factors providing broad hereditary heterogeneity of schizophrenia.     

Phenological responses in a sycamore–aphid–parasitoid system and consequences for aphid population dynamics: A 20 year case study

Species interactions have a spatiotemporal component driven by environmental cues, which if altered by climate change can drive shifts in community dynamics. There is insufficient understanding of the precise time windows during which inter‐annual variation in weather drives phenological shifts and the consequences for mismatches between interacting species and resultant population dynamics—particularly for insects. We use a 20 year study on a tri‐trophic system: sycamore Acer pseudoplatanus, two associated aphid species Drepanosiphum platanoidis and Periphyllus testudinaceus and their hymenopteran parasitoids. Using a sliding window approach, we assess climatic drivers of phenology in all three trophic levels. We quantify the magnitude of resultant trophic mismatches between aphids and their plant hosts and parasitoids, and then model the impacts of these mismatches, direct weather effects and density dependence on local‐scale aphid population dynamics. Warmer temperatures in mid‐March to late‐April were associated with advanced sycamore budburst, parasitoid attack and (marginally) D. platanoidis emergence. The precise time window during which spring weather advances phenology varies considerably across each species. Crucially, warmer temperatures in late winter delayed the emergence of both aphid species. Seasonal variation in warming rates thus generates marked shifts in the relative timing of spring events across trophic levels and mismatches in the phenology of interacting species. Despite this, we found no evidence that aphid population growth rates were adversely impacted by the magnitude of mismatch with their host plants or parasitoids, or direct impacts of temperature and precipitation. Strong density dependence effects occurred in both aphid species and probably buffered populations, through density‐dependent compensation, from adverse impacts of the marked inter‐annual climatic variation that occurred during the study period. These findings explain the resilience of aphid populations to climate change and uncover a key mechanism, warmer winter temperatures delaying insect phenology, by which climate change drives asynchronous shifts between interacting species.     

Segregation of HLA A,B haplotypes and the distribution of antigen mismatches between mother and offspring in Hutterite families

Segregation of HLA haplotypes and offspring genotype distributions were analyzed in families from an inbred Caucasoid population, the Dariusleut Hutterite Brethren. Both parents and from one to 12 offspring were typed for HLA-A and -B antigens in 108 families. Segregation of paternal haplotypes was analyzed conditional on sibship size in 95 sibships (a total of 547 offspring), and segregation of maternal haplotypes, in 90 sibships (a total of 515 offspring). The distribution of the number of different genotypes among the offspring was analyzed conditional on sibship size in 90 families (515 offspring) where four equiprobable genotypes were expected. The distribution of the number of antigenic differences or mismatches for broad specificities between mother and offspring was analyzed in pooled family data consisting of a total of 377 offspring comprising 68 families. Compared with the multinomial distribution of segregation classes of haplotypes, there was no significant departure (probability .05 or less) from the expected segregation ratio for either paternal or maternal haplotypes. Compared with the multinomial distribution of the number of genotypes among the offspring, only two of the 11 sibship sizes had configurations that exceeded the 5% level of significance. Given the number of statistical tests performed, it is likely that these results could be explained by chance variation. Finally, there was no relative deficiency of offspring who were less mismatched with their mother for HLA-A and -B broad specificities. Therefore, if HLA-A,B region variation does have a major effect on the differential survival of fetuses in some families, it is an uncommon factor among fertile couples from this inbred population.     

Association of Hereditary Nonpolyposis Colorectal Cancer–Related Tumors Displaying Low Microsatellite Instability with MSH6 Germline Mutations

Hereditary nonpolyposis colorectal cancer (HNPCC) (Amsterdam criteria) is often caused by mutations in mismatch repair (MMR) genes, and tumors of patients with HNPCC show microsatellite instability (MSI-high phenotype). Germline mutations of MMR genes have rarely been found in families that have HNPCC or suspected HNPCC and that do not show microsatellite instability (MSI-low phenotype). Therefore, an MSI-high phenotype is often used as an inclusion criterion for mutation testing of MMR genes. Correction of base-base mismatches is the major function of MSH6. Since mismatches present with an MSI-low phenotype, we assumed that the phenotype in patients with HNPCC-related tumors might be associated with MSH6 germline mutations. We divided 36 patients with suspected HNPCC into an MSI-low group (n=18) and an MSI-high group (n=18), on the basis of the results of MSI testing. Additionally, three unrelated patients from Amsterdam families with MSI-low tumors were investigated. All patients were screened for MSH2, MLH1, and MSH6 mutations. Four presumably causative MSH6 mutations were detected in the patients (22%) who had suspected HNPCC and MSI-low tumors. Furthermore, we detected one frameshift mutation in one of the three patients with HNPCC and MSI-low tumors. In the MSI-high group, one MSH6 missense mutation was found, but the same patient also had an MLH1 mutation, which may explain the MSI-high phenotype. These results suggest that MSH6 may be involved in a substantial proportion of patients with HNPCC or suspected HNPCC and MSI-low tumors. Our data emphasize that an MSI-low phenotype cannot be considered an exclusion criterion for mutation testing of MMR genes in general.     

Predictors of drop-out in a multi-centre longitudinal study of participation and quality of life of children with cerebral palsy

ABSTRACT: BACKGROUND: SPARCLE is a study across nine European regions which examines the predictors of participation and quality of life of children with cerebral palsy. Children and their families were initially interviewed in 2004/2005 when the children were aged 8-12 years (SPARCLE1); they were approached again in 2009/2010 at age 13-17 years (SPARCLE2). The objective of this report is to assess potential for bias due to family non-response in SPARCLE2. Logistic regression was used to assess whether socio-demographic factors, parental stress and child impairment were related to non-response, both overall and by category (failure to trace families, death of child, traced families declining to participate). RESULTS: Of the 818 families who participated in SPARCLE1, 224/818 (27%) did not participate in SPARCLE2. 51/818 (6%) were not traced. Among the 767 traced families, 32/767 (4%) children with cerebral palsy had died, seven children had been incorrectly diagnosed as having cerebral palsy, thirteen families had moved out of the region and one family had language problems. Of the remaining 714 families, 120/714 (17%) declined to participate. Drop-out between SPARCLE1 and SPARCLE2 varied significantly between regions; families were more difficult to trace and more likely to decline to participate if the parents' educational qualifications, as recorded in SPARCLE1, were lower; they were also more likely to decline to participate if SPARCLE1 recorded that they were more stressed or if they had not completed a SPARCLE1 stress questionnaire. CONCLUSIONS: To reduce the risk of bias, all SPARCLE2 analyses should allow for factors (region and walking ability) which determined the sampling strategy, either by adjusting for these factors or by using sampling weights. Further analyses should be performed, adjusting for additional factors that were associated with non-response: parents' educational qualifications, family structure and parental stress. To allow for differential non-response in studies which sample from population registers, such registers should routinely record socio-demographic information.     

Correlation of parental socioeconomic status indicators with morphological and motor dimensions of preschool children

Measuring instruments for assessment of parental socioeconomic status, anthropometric characteristics and motor abilities were used in a sample of 643 preschool children aged 4-6 years and their parents, recruited from preschool institutions in several towns in Voivodina, Serbia. The aim was to analyze the correlation of parental socioeconomic status indicators with morphological and motor dimensions of preschool children. Study results showed the socioeconomic status of the children's families to be relatively homogeneous, with no statistically significant differences in any of the socioeconomic status indicators between families with male and female children. Male and female children differed significantly in the overall space of anthropometric and motor variables, and to a lesser extent in individual variables. The general morphological factor treated as the children's growth and development, and general motor factor were qualitatively comparable. The correlations of socioeconomic factor with general morphological and motor factors of the children were not statistically significant, with the exception of motor factor in 6-year-old male children, at elementary school enrolment. Study results suggested the differences in biological growth and development and motor development recorded in preschool children from Voivodina, Serbia, to be attributable to hereditary factor rather than socioeconomic and environmental factors. Inclusion of older children and use of more socioeconomic status indicators along with some additional indicators should probably yield more reliable results on the issue.