Special twin environments, genetic influences and their effects on the handedness of twins and their siblings.

It has been suggested that twinning may influence handedness through the effects of birth order, intra-uterine crowding and mirror imaging. The influence of these effects on handedness (for writing and throwing) was examined in 3657 Monozygotic (MZ) and 3762 Dizygotic (DZ) twin pairs (born 1893-1992). Maximum likelihood analyses revealed no effects of birth order on the incidence of left-handedness. Twins were no more likely to be left-handed than their singleton siblings (n = 1757), and there were no differences between the DZ co-twin and sibling-twin covariances, suggesting that neither intra-uterine crowding nor the experience of being a twin affects handedness. There was no evidence of mirror imaging; the co-twin correlations of monochorionic and dichorionic MZ twins did not differ. Univariate genetic analyses revealed common environmental factors to be the most parsimonious explanation of familial aggregation for the writing-hand measure, while additive genetic influences provided a better interpretation of the throwing hand data.     

Twins,triplets, and cerebral palsy in births in Western Australia in the 1980s.

OBJECTIVES--To examine the rate of cerebral palsy in twins and triplets in births from 1980 to 1989 in Western Australia and to identify factors associated with increase in risk. DESIGN--Pluralities for all births in Western Australia were identified through the standardised midwives'' notification system, and cases of cerebral palsy were identified from the Western Australian cerebral palsy register. MAIN OUTCOME MEASURES--Multiple births, cerebral palsy, excluding postneonatal cause. RESULTS--The prevalence of cerebral palsy in triplets, of 28 per 1000 survivors to 1 year (95% confidence interval 11 to 63) exceeded that in twins (7.3; 5.2 to 10) and singletons (1.6; 1.4 to 1.8). Although twins and triples were more likely than singletons to be low in birth weight, their risks of cerebral palsy if low in birth weight were similar. In contrast, in normal birthweight categories twins had a higher rate of cerebral palsy (4.2; 2.2 to 7.7) than singletons (1.1; 1.0 to 1.3). The prevalence of cerebral palsy was similar in twins of unlike sex pairs, all of whom are dizygotic, and in like sex pairs. A twin pair in which one member died in utero was at higher risk of cerebral palsy: 96 per 1000 twin pairs (36 to 218) compared with 12 (8.2 to 17) for twin pregnancies in which both survived. There was a similar but non-significant trend for death of one triplet to be associated with increased risk of cerebral palsy in the survivors of the set. CONCLUSION--Triplet pregnancies produced a child with cerebral palsy 47 times more often than singleton pregnancies did and twin pregnancies eight times more often. Eighty six per cent of cerebral palsy in multiple births was in twins. As multiple births are increasing mainly because of personal and medical decisions the increased risk of cerebral palsy in multiple births is of concern.     

Behavioral inhibition as a function of relationship in preschool twins and siblings.

Monozygotic (MZ) twins spend more time with each other and are more genetically alike than are dizygotic (DZ) twins or nontwin siblings and therefore probably experience less diversity in their playmates than DZ twins, who in turn may experience less diversity than other-age siblings. Thus MZ twins may be more inhibited than DZ twins, who may in turn be more inhibited than nontwin siblings. To test this, 205 children (42 MZ twins, 94 DZ twins, and 69 nontwin siblings) were assessed in a playroom laboratory during free play with an unfamiliar peer. Children's inhibition was rated based on latency to touch a toy for the first time and amount of time spent interacting with the other child. Additionally, the Child Behavior Checklist (CBCL) withdrawn scale was used to assess inhibition according to parent report. Behavioral ratings showed that MZ and DZ twins did not significantly differ on the inhibition or withdrawn ratings. DZ twins were significantly more inhibited than were nontwin siblings, according to laboratory ratings. Greater inhibition of twins during the free peer play situation can be explained by their relative lack of experience in playing with children who are less genetically and phenotypically like themselves. Parental ratings showed exactly the opposite pattern, suggesting a rater bias effect.     

METALGEN.DB: metabolism linked to the genome of Escherichia coli, a graphics-oriented database

The table of ‘biochemical pathways’ published byBoehringer is considered as the most exhaustive document dealingwith intermediary metabolism. The present work consisted ofconstructing a database in which is collected everything knownto date about intermediary metabolism: metabolic path bioreactions,metabolites, enzymatic activities, genes and regulation. Dataon genes make it possible to establish a link with existingcomputer structures specialized for genomic sequences. The presentstructure of the database presented here consists of three environments.The first environ is graphic; it is modeled upon the Boehringertable, but is more convenient to use. The second environmentprovides the user with all kinds of manipulations of data (entries,corrections, deletions, consistency, limiting redundancy, etc.).These operations either are automatic or depend on a user-friendlyinterface (menus selected with the mouse) and so allow biologistsat all levels to use the database and to develop it for theirown particular needs. Finally, the third environment offersrious procedures that make it possible to carry out multicriteriaresearch on all the data in the database at once. This databasecan thus be substituted for the Boehringer table as a standardreference. It is also a tool that can be used to develop informationsystems not only in the domain of metabolism but also in thestudy of genomes (modeling, analysis of data, predictions, etc.).     

Population based study of rates of multiple pregnancies in Denmark, 1980-94.

OBJECTIVE: To study trends in multiple pregnancies not explained by changes in maternal age and parity patterns. DESIGN: Trends in population based figures for multiple pregnancies in Denmark studied from complete national records on parity history and vital status. POPULATION: 497,979 Danish women and 803,019 pregnancies, 1980-94. MAIN OUTCOME MEASURES: National rates of multiple pregnancies, infant mortality, and stillbirths controlled for maternal age and parity. Special emphasis on primiparous women > or = 30 years of age, who are most likely to undergo fertility treatment. RESULTS: The national incidence of multiple pregnancies increased 1.7-fold during 1980-94, the increase primarily in 1989-94 and almost exclusively in primiparous women aged > or = 30 years, for whom the adjusted population based twinning rate increased 2.7-fold and the triplet rate 9.1-fold. During 1989-94, the adjusted yearly increase in multiple pregnancies for these women was 19% (95% confidence interval 16% to 21%) and in dizygotic twin pregnancies 25% (21% to 28%). The proportion of multiple births among infant deaths in primiparous women > or = 30 years increased from 11.5% to 26.9% during the study period. The total infant mortality, however, did not increase for these women because of a simultaneous significant decrease in infant mortality among singletons. CONCLUSIONS: A relatively small group of women has drastically changed the overall national rates of multiple pregnancies. The introduction of new treatments to enhance fertility has probably caused these changes and has also affected the otherwise decreasing trend in infant mortality. Consequently, the resources, both economical and otherwise, associated with these treatments go well beyond those invested in specific fertility enhancing treatments.     

Comparing blood pressure of twins and their singleton siblings: being a twin does not affect adult blood pressure.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.     

Maternal age and birth weight characteristics of twins born to nulliparous mothers: a population study.

In order to examine birth weight characteristics of twins delivered to nulliparous mothers in relation to maternal age, we used a population-based cohort of Israeli twins delivered between 1993-98 to select all 4793 (37.6%) nulliparas who delivered twins. Maternal age was subdivided as less than 20 years, 20-24, 25-29, 30-34, 35-39, and 40 years or more. We counted the frequencies of each total twin birth weight (twin A + twin B) in each of three categories (less than 3000, 3000-4999, and more than 5000 g) and the frequency of very low birth weight (VLBW, less than 1500 g) neonates in each of the six maternal age categories. There were significantly more nulliparas in the twin population at age groups less 30 years and significantly less at ages 30 years or more. We found a highly significant inverse correlation between the proportion of nulliparas and maternal age group, decreasing from 71.8% at less than 20 years to 18.6% at age 35-39 years (% nulliparas = 85 - 13.7 x age group, Pearson R2 = 0.98). However, this trend changed abruptly to the observed figure of 25.9% nulliparas aged 40 years or more instead of the expected 2.8%. We failed to reveal any significant difference in birth weight characteristics between the maternal age groups (all p > 0.05, all confidence intervals included 1.0). The more than tenfold deviation of the observed from the predicted frequency of nulliparas aged 40 years or more suggests that a different relationship between parity and age occurs at this age group. Maternal age of nulliparas is not associated with different birth weight characteristics of their twins.     

Agarose linked adenosine and guanosine-5''-monophosphate; a new general method for the coupling of ribonucleotides to polymers through their cis-diols.

Condensation of the cis-diol of adenosine (1a) or guanosine (1b) with ethyl levulinate led to the acetal-esters 2a or 2b. Phosphorylation with phosphorous oxide trichloride converted them into their 5'-monophosphates. On alkaline hydrolysis the acetal-esters 2a,b as well as their 5'-monophosphates gave the carboxylic acid derivatives 3a,b and 4a,b, respectively. Condensation of these acid derivatives with aminohexyl-agarose (5) using water soluble N-ethyl-N'-(3'-dimethyl-aminopropyl)-carbodiimide hydrochloride as coupling reagent led to the new polymers 6a/6b and 7a/7b. This method of preparing resin linked adenosine and guanosine derivatives should be generally applicable to any ribonucleoside or ribonucleotide with a cis-diol. Because of the widespread occurence of these molecules, particularly as cofactors of enzymes, the new polymers might be useful tools for the purification of certain classes of enzymes by affinity chromatography.     

Cross-cultural adaptation and preliminary validation of a zygosity determination questionnaire for twins in Sri Lanka.

We report the process of adaptation into Sinhala of a questionnaire given to mothers of twins to determine zygosity. Adaptation and validation was carried out in three stages. Firstly, we used a nominal group to translate the English version and to assess the extent of agreement (consensus measurement) on the appropriateness of the translation and resolve disagreement (consensus development). Secondly we used a qualitative interview with 25 mothers of twins. The three main stems of the translated questionnaire were used as a semi-structured interview, and the responses noted verbatim. These were categorised and analysed, and the translated full questionnaire was then presented as closed questions with fixed choice responses. The categorised responses generated during the qualitative interview were compared with the responses to the fixed choices in the full questionnaire. The third stage was the appraisal of the questionnaire by 17 bilingual parents of twins. The source and translated version of the questionnaire were given to them at least 3 days apart. The responses were rated and the total scores were computed to determine the zygosity. This step was carried out to measure the validity and reliability of the Sinhala version. A perfect correlation between the original and adapted version was obtained, with a kappa of 1. The results suggest that the Sinhala version of the questionnaire is conceptually equivalent to the original questionnaire. Comparison of the zygosity determination by using this adapted questionnaire with results from analysis of genetic markers on Sri Lankan twins is needed for final validation of the translated questionnaire.     

A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs.

Important risk factors for melanoma are densely clustered melanocytic nevi (common moles) and mutations in the p16 (CDKN2A) gene. Nevi may be subclassified as raised or flat. In our sample, raised nevi were 27% of the total, and the two kinds had a correlation of.33. Correlations for total-nevus count (TNC) in 153 MZ and 199 DZ twin pairs were.94 and.60, respectively, which are compatible with a very-high degree of genetic determination. We hypothesized that some of the genetic variance might be due to variation in the p16 gene. Analysis of linkage to a highly polymorphic marker (D9S942), located close to p16, detected quantitative-trait-loci (QTL) effects accounting for 27% of variance in TNC, rising to 33% if flat but not raised moles were considered. Total heritability was higher for raised (.69) than for flat (.42) moles, but QTL linkage was 0 for raised moles, whereas it accounted for 80% of the heritability of flat moles; additionally, family environment accounted for only 15% of variance in raised versus 46% in flat moles. These findings suggest that raised and flat nevi have very different etiologies. Longer alleles at D9S942 were associated with higher flat-mole counts, and a novel modification to a within-sibship association test showed that this association is genuine and not due to population stratification, although it accounts for only 1% of total variance. Since germline mutations in the exons of CDKN2A are rare, it is likely that variants in the noncoding regions of this gene, or in another gene nearby, are responsible for this major determinant of moliness and, hence, of melanoma risk.     

Palaeomagnetic results from sediments of the Perth Basin,Western Australia,and their bearing on the timing of regional lateritisation

In an attempt to extend palaeomagnetic investigation of Late Palaeozoic and Mesozoic rock formations in Australia, 222 oriented samples have been collected from sedimentary horizons in the Perth Basin and adjacent areas. The thermal stability of the remanent magnetism has been established, but its direction remained oriented close to the direction of the present local geomagnetic field, irrespective of the age of formation sampled. Further attempts to partially demagnetise some specimens using chemical techniques also failed to isolate the primary component of magnetisation. The results have been interpreted as indicating an episode of “blanket” remagnetisation which occurred during the period of regional lateritisation. The presence of normal and reversed polarities indicates that remagnetisation occurred over an extended period of time. By comparing the paleomagnetic pole positions with the apparent polar-wander curve recognised for the Cenozoic of Australia, quantitative support for a Late Oligocene to Early Miocene age for the period of lateritisation is given. Other palaeomagnetic evidence suggests this age may be correlated to laterites in Northern Territory.     

Population structure of Macrobrachium australiense (Decapoda: Palaemonidae) in Western Queensland, Australia: the role of contemporary and historical processes

Rivers of Western Queensland, Australia, represent a discontinuous and variable aquatic habitat for the freshwater fauna of the region. Rivers periodically fluctuate between being highly fragmented, with numerous disconnected waterholes and ephemeral channels, and being highly connected by a dominant system of anastomosing channels. We used mitochondrial sequences to investigate the genetic structure and inferred patterns of dispersal associated with this flow regime for the freshwater prawn, Macrobrachium australiense (Decapoda: Palaemonidae), sampling 28 localities throughout eight catchments. Based on a 505 base pair fragment of mitochondrial cytochrome c oxidase subunit I, we identified 98 haplotypes in a sample of 402 individuals. The haplotypes clustered into two main clades corresponding geographically to the major drainages: the Lake Eyre and Murray-Darling basins. Populations of M. australiense inhabiting the two basins appear to have diverged around 800,000 years ago (estimated sequence divergence of 1.6%). Analysis of population differentiation indicated contemporary high levels of genetic subdivision and restricted gene flow among populations within and among catchments. Phylogenetic analysis detected a series of historical range expansions in the region and we suggest that climate fluctuations during the Pleistocene have resulted in extensive floods that have promoted historical movements of aquatic organisms across catchment boundaries.     

Hospital Utilisation in Indigenous and Non-Indigenous Infants under 12 Months of Age in Western Australia,Prospective Population Based Data Linkage Study

BackgroundIndigenous infants (infants aged under 12 months) have the highest hospital admission and emergency department presentation risks in Australia. However, there have been no recent reports comparing hospital utilisation between Indigenous and non-Indigenous infants.MethodsOur primary objective was to use a large prospective population-based linked dataset to assess the risk of all-cause hospital admission and emergency department presentation in Indigenous compared to non-Indigenous infants in Western Australia (WA). Secondary objectives were to assess the effect of socio-economic status (Index of Relative Socio-Economic Disadvantage [IRSD]) on hospital utilisation and to understand the causes of hospital utilisation.FindingsThere were 3,382 (5.4%) Indigenous and 59,583 (94.6%) non-Indigenous live births in WA from 1 January 2010 to 31 December 2011. Indigenous infants had a greater risk of hospital admission (adjusted odds ratio [aOR] 1.90, 95% confidence interval [95% CI] 1.77–2.04, p = <0.001) and emergency department presentation (aOR 2.15, 95% CI 1.98–2.33, p = <0.001) compared to non-Indigenous infants. Fifty nine percent (59.0%) of admissions in Indigenous children were classified as preventable compared to 31.2% of admissions in non-Indigenous infants (aOR 2.12, 95% CI 1.88–2.39). The risk of hospital admission in the most disadvantaged (IRSD 1) infants in the total cohort (35.7%) was similar to the risk in the least disadvantaged (IRSD 5) infants (30.6%) (aOR 1.04, 95% CI 0.96–1.13, p = 0.356).InterpretationWA Indigenous infants have much higher hospital utilisation than non Indigenous infants. WA health services should prioritise Indigenous infants regardless of their socio economic status or where they live.