Genetic composition of Jewish populations: diversity and inbreeding

Genetic diversity and F statistics analysis, using 9 and 5 blood group loci, respectively, were carried out on 16 Jewish populations from 5 geographic regions: East Europe, Central Europe, South Europe, Middle East and North Africa. The proportion of total diversity found within populations was 98.9% while that between populations, within geographic groups and between groups altogether was only 1.1%. The average heterozygosity between geographic groups ranged from 0.3867 to 0.4150. There were no significant differences between geographic groups of populations in heterozygosity or in its variance. Average estimates of inbreeding were as follows: Fis = 0.0419, Fst = 0.0084 and Fit = 0.0498. Because the heterogeneity and relative proportion of diversity were less between Jewish populations than between non-Jewish ones, we conclude that genetic similarity between Jews is higher than between Gentiles. The findings are in agreement with our previously obtained calculations of genetic distances (Kobyliansky, Micle, Goldschmidt-Nathan, Arensburg and Nathan 1982).     

The use of parental isonymy in inbreeding in two Outer Hebridean populations

The use of isonomic associations between the parents of spouses is described. Scottish marriage registers contain information on the natal surnames of all four parents of spouses and enable all the four possible types of isonymy between pairs of parents to be identified. Thus assumptions about the sex labelling of pedigrees may be tested and inbreeding coefficients calculated using either each type of isonymy singly or by pooling all types to give 'overall' coefficients. By this latter method the number of potential isonomous events is increased to four times the number of marriages. Assumptions about the randomness of migration with regard to sex may also be tested by comparing coefficients of relationship by isonymy calculated using either paternal or maternal natal surnames. Within populations the coefficients should be lower for the more migrant sex: between populations the reverse should be the case. Similarly the intergenerational 'fluxes' of surnames in parents of either sex may be compared as may be similar variation in surname frequencies. Two small Outer Hebridean islands, Scalpay and Berneray were used to test these assumptions. It was concluded that while the sex labelling of pedigrees appeared to be at random, there was considerable variation in the isonymy inbreeding coefficients and that because of the 4 X greater amount of data, 'overall' coefficients are more reliable. In both islands there appeared to be a greater lability in migrational terms of the female population, although it was impracticable to examine all marriages involving residents of the two islands.     

Estimating inbreeding in large, semi-isolated populations: effects of varying generation lengths and of migration.

The purpose of the study reported here was to investigate two important assumptions used in a recently reported new method of estimating inbreeding in large, relatively isolated populations over historic times. The method, based on modeling the genealogical "paradox," produces values of Pearl's coefficients, Z, a measure of inbreeding or genealogical coalescence, as a function of time. In this study, the effects on inbreeding of two important assumptions made in earlier studies, namely those of using a constant generation length and of ignoring migration, have been investigated for the population of Britain. First, by relating the median age of women at childbirth to the development level of various societies, the variation of the generation lengths for different periods in historic Britain were estimated. Values of Z for two types of varying generation lengths were then calculated and compared with the case of constant generation length. Second, the population curve for Britain used in earlier studies was modified to obtain the subpopulation at any time during the past two millennia that was descended from the pre-Roman British Celts. Values of Z for the case with migration were then calculated and compared with the case for no migration. It is shown that these two assumptions may be taken into account if and when required. Both the effect of a varying generation length and the effect of migration on Z were found to be 20-40%, when no known value of inbreeding was used, and 2-5%, when a known value of inbreeding was used.     

Estimation of respiratory parameters via fuzzy clustering

The results of monitoring respiratory parameters estimated from flow-pressure-volume measurements can be used to assess patients' pulmonary condition, to detect poor patient-ventilator interaction and consequently to optimize the ventilator settings. A new method is proposed to obtain detailed information about respiratory parameters without interfering with the expiration. By means of fuzzy clustering, the available data set is partitioned into fuzzy subsets that can be well approximated by linear regression models locally. Parameters of these models are then estimated by least-squares techniques. By analyzing the dependence of these local parameters on the location of the model in the flow-volume-pressure space, information on patients' pulmonary condition can be gained. The effectiveness of the proposed approaches is demonstrated by analyzing the dependence of the expiratory time constant on the volume in patients with chronic obstructive pulmonary disease (COPD) and patients without COPD.     

Estimation of quantitative genetic parameters under non-normal models

In traditional quantitative genetics, the relationship between the observed value of a quantitative trait in a set of families and its genetic and environmental contributions can be described as a linear additive relationship. Generally, it is assumed that the genetic and environmental effects are independent and normally distributed. Consequently, the quantitative trait also has a normal distribution. However, there are some situations where the phenotype does not follow the normal distribution. To deal with this problem the author suggests the families of distributions that belong to the Johnson Translation System (JTS). As an example, two dependent quantitative traits, weight and height, are investigated assuming that they have a lognormal and normal distribution, respectively. Computational methods for estimating the genotypic variances and covariances are presented.     

Estimation of parameters in transcapillary fluid movement by digital simulation

A modified computer model of the terminal vascular bed is presented. The capillary model consists of two parts; the arterial and venous capillary segments in series with the corresponding resistances. A third segment, in parallel with the capillary, represents the varying volume interstitial space. In addition to equations describing the fluid flow between the various segments, the dynamics of protein-mass flow are described. In contrast to models described by earlier investigators, the plasma osmotic pressure π_PL is also a variable. Thus, small changes in π_PL due to variations in venous pressure could be detected. The percentage increase in π_PL per mm Hg increase in venous pressure has an average value of 0·255% per mm Hg. Finally, a hysteresis phenomenon was demonstrated while increaseing and decreasing extravascular tissue volume; the total simulated energy expenditure was EH=1·542 mm Hgx ml for a venous pressure change from 5 to 20 mm Hg. An abbreviated report was presented at the 3rd Annual Meeting of the Biomedical Engineering Society, 7th April, Baltimore, Md., USA     

Estimation of tissue parameters derived from reflected ultrasound

We propose a method of estimating two tissue parameters, that is, the reflection coefficient and attenuation coefficient from the reflected ultrasound for the purpose of improving the resolution of ultrasonic images and obtaining information on tissue characterization. The reflection coefficient is estimated by deconvolution technique using Kalman filter taking into account the distortion of the propagating pulse due to the frequency-dependent attenuation. The attenuation is estimated by adaptive processings based upon the criterion function calculated using estimates of the reflection coefficient. Simulated signals are used to investigate the ability of this method. Additionally, actual reflected signals from soft tissues are processed by the method. The results show that the method can be applied in clinical cases.     

Five landmarks in inbreeding studies

A short review is made on papers by Mendel, Wright, Haldane and Moshinsky, Cotterman, Malécot, Morton et al., and Khoury et al. The accompanying paper applies the two epidemiological approaches of this paper to the Brazilian populations.     

Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations

We describe a novel method for analysis of marker genotype data from admixed populations, based on a hybrid of Bayesian and frequentist approaches in which the posterior distribution is generated by Markov chain simulation and score tests are obtained from the missing-data likelihood. We analysed data on unrelated individuals from eight African-American populations, genotyped at ten marker loci of which two ( FY and AT3 ) are linked (22 cM apart). Linkage between these two loci was detected by testing for association of ancestry conditional on parental admixture. The strength of this association was consistent with European gene flow into the African-American population between five and nine generations ago. To mimic the mapping of an unknown gene in an 'affecteds- only' analysis, a binary trait was constructed from the genotype at the AT3 locus and a score test was shown to detect linkage of this 'trait' with the FY locus. Mis-specification of the ancestry-specific allele frequencies – the probabilities of each allelic state given the ancestry of the allele – was detected at three of the ten marker loci. The methods described here have wide application to the analysis of data from admixed populations, allowing the effects of linkage and population structure (variation of admixture between individuals) to be distinguished. With more markers and a more complex statistical model, genes underlying ethnic differences in disease risk could be mapped by this approach.