Inbreeding in outport Newfoundland

We investigated inbreeding in 3 outport Newfoundland study areas in which persistent genetic isolation was demonstrated previously. The inbreeding coefficient of every person born in each area was calculated from reconstructed pedigree data. The average inbreeding coefficient for persons born between 1960 and 1979 is 0.0032 in Trepassey Parish (southern Avalon Peninsula), 0.0171 for a group of communities on the west coast of the Great Northern Peninsula, and 0.0007 for southeastern Labrador. Average inbreeding of these populations was higher earlier in this century. Averages are high compared to those reported for other populations, consistent with genetic isolation. Coefficients of kinship were calculated for large samples of pairs of births in each study area, and frequency distributions of inbreeding coefficients compared with frequency distributions of kinship coefficients, to evaluate random and nonrandom mating with respect to consanguinity. These comparisons show that matings between unrelated individuals are more frequent than expected, that matings between first cousins are not strongly avoided in 2 of the 3 study areas, that matings between first cousins once removed are favored, and that matings between distantly related individuals are becoming more frequent. To gain an impression of the potential contribution of inbreeding to the prevalence of recessive disease, we calculated indirect estimates of the expected excess of prereproductive mortality due to inbreeding. These estimates are 15% for Trepassey Parish, 49% for the West Coast study area, and 2% for southeastern Labrador. It is unlikely that genetic isolation of outport Newfoundland populations will decrease. Elevated prevalences of recessive disease, due primarily to matings between persons unaware of their distant consanguinity, therefore require consideration in health care planning in Newfoundland.     

Marital migration and genetic structure in Kitee, Finland

A genetic analysis of marital migration in Kitee, Finland, is presented. The data are based on 9970 marriages which took place between 1750 and 1877. The results of this analysis are compared with those of previous studies of the population of the Aland Islands, Finland. Analysis of inter-subdivision genetic kinship matrices shows that genetic heterogeneity in Kitee is substantially less than in Aland. This is due primarily to higher rates of migration, both between subdivisions and from outside the population, in Kitee compared to Aland. These differences in migration rates can in turn be attributed to greater geographic isolation in Aland and the contrasting social structures of the two populations. Because of differences in geographic structure and population distribution, geographic distance between subdivisions is a better predictor of inter-subdivision genetic kinship in Kitee than in Aland. The Aland Islands are known to have high frequencies of several otherwise rare genetic diseases; in addition, these diseases are distributed very non-randomly among Aland's subdivisions. The genetic structure results presented here suggest that Kitee should have a less unique distribution of genetic diseases.     

Surnames in Sardinia II. Computation of migration matrices from surname distributions in different periods

A method is described for obtaining migration matrices from data on frequency distributions of transmissible traits in at least two different periods. In the present case, surname frequency distributions were used. In this way migration matrices describing rates of movement among nine areas of Sardinia were found for the period 1850–1970. Data were kinship matrices from surname distributions over two or three time periods. Population growth was included in the model under the assumption that expected family size in all areas was constant, or that outside estimates of the relative family sizes exist. Use of variable vs. constant growth rates did not drastically affect the estimated matrices.
The matrices estimated for different time periods are similar. Estimates of net migration into the different areas were relatively insensitive to different methods of summarizing statistics.
The elements of the matrices indicate strong effects on migration rates of distance between areas, and somewhat weaker effects of economic differences. The diagonal elements of the matrices show a high negative correlation with independent estimates of rates of immigration into the same areas.     

Inbreeding in the Utah Mormons: an evaluation of estimates based on pedigrees, isonymy, and migration matrices

Using a computerized genealogical database, inbreeding coefficients were calculated for a sample of 435777 Utah Mormons. The population was divided into ten ten-year birth cohorts (1846–1945) and 22 geographic subdivisions in order to assess temporal and spatial variation in inbreeding. The average inbreeding coefficient for this population is 0.000 106. The average within-groups random kinship coefficient is 0.000 312, reflecting consanguinity avoidance. Random kinship matrices were formed by estimating the average kinship within each spatial subdivision and between all pairs of subdivisions. These matrices were compared statistically with kinship matrices previously estimated using migration matrices and isonymy data. The isonymy approach consistently overestimates random and total inbreeding as well as Wright's F_st. This can be attributed primarily to the assumption of monophyletic origin of surnames. The migration matrix method underestimates random inbreeding and F_st. This is due mainly to the assumption that outside immigrants are derived from a genetically homogeneous population. While the absolute values of the kinship coefficients estimated by each method differ substantially, the patterns of between-groups kinship coefficients given by each method are highly congruent. Logistic and linear regression analyses of 85 235 marriages demonstrate that consanguinity is significantly dependent upon year of marriage, geographic distance between husband's and wife's birthplaces, and the population size of husband's and wife's birthplaces.     

The role of kin-structured migration in genetic microdifferentiation

Most current models of human population structure view migration solely as a deterministic force reducing the variance in gene frequencies among the local colonies of a subdivided population. By an empirical example and through simulation experiments, it is shown that migration structured along kinship lines (by analogy to the lineal or ‘kinship’ effect) does not always reduce the variances of gene frequencies arising through intergenerational random genetic drift. Thus populations experiencing high rates of migration may not be genetically homogenous.     

Kinship by isonymy and by gene frequencies: A comparison of population structures at different hierarchical population levels

A comparison of population structures based on isonymy and on gene frequencies (ABO, Rh, Kell) was conducted for a sample of 28,205 individuals residing in three different provinces (Lucca, Massa Carrara, La Spezia) in northwest Italy, on the basis of both chronological and spatial subgroupings. Relationships between and within population subsamples were measured by means of kinship coefficients. The aim of this study was focused on kinship decay with geographic distance, associated with the great difference in location and variability between isonymic and genetic data. The analysis was carried out by R_st statistics and regression analysis to test the fit of the isolation by distance models. Further, the R matrices were converted into a distance measure, and Mantel's permutation test was used to assess the correlation across isonymy, genetic, and geographic matrices. Whereas estimates of R_st and isolation by distance parameters obtained from genetic and surname data pointed to a roughly comparable basic pattern of spatial differentiation in both chronological periods, the absolute values differ substantially. Both R_st and a isolation by distance parameters estimated from genetic data were higher than those from surnames, indicating greater local isolation by genetic analysis. The standard errors of b obtained from surname data were much smaller than those computed from genetic data, indicating that the kinship by isonymy coefficients fit Malècot's model better than the kinship coefficients estimated by the genetic data. Squared correlation coefficients among geographic, surname, and genetic distance matrices supported the above interpretations. The strong localization of surnames, the different level of variability in surname and gene frequency data, and random variations (due to the number of alleles considered) seem to be the main reasons for the observed differences between the two data sets. © 1996 Wiley-Liss, Inc.     

Toward cultural competence in cancer genetic counseling and genetics education: lessons learned from Chinese-Australians.

PURPOSE: In societies such as Australia with a strong multicultural makeup, culturally determined attitudes to genetics, testing, and counseling may be incompatible with current genetics service provision. METHODS: An ethnographic investigation using purposive sampling to increase subject diversity was used to explore the range of beliefs about kinship and inheritance using Chinese-Australians as a case. Participants comprised a sample of 15 Chinese-Australians who had been recruited through several community-based organizations. RESULTS: The level of acculturation does not correlate with holding beliefs about inheritance, kinship, and causes of hereditary cancer that are based on "Western" biomedical or traditional concepts. Mismatch between beliefs may exist within families that can impact participation in cancer genetic testing. Family history taking that underpins the surveillance, management, and referral to genetic counseling where there is a strong family history of breast, ovarian, or colorectal cancer can also be impacted unless recognition is made of the patrilineal concept of kinship prevalent in this Chinese-Australian community. CONCLUSION: This community-based study confirmed and validated views and beliefs on inheritance and kinship and inherited cancer attributed to senior family members by Chinese-Australians who attended cancer genetic counseling. Barriers to communication can occur where there may be incompatibility within the family between "Western" and traditional beliefs. The findings were used to develop strategies for culturally competent cancer genetic counseling with Australian-Chinese patients. These include nonjudgmental incorporation of their belief systems into the genetic counseling process and avoidance of stereotyping. They have also influenced the development of genetics education materials to optimize family history taking.     

Population structure of the Juang tribe in Orissa,India

The coefficient of kinship of the Juangs, a very primitive tribe in the state of Orissa in eastern India, is estimated. The Juang population is sub-divided into two breeding groups: one practising shifting cultivation in the hilly regions of the former state Keonjher and Pal-Lahara, called here “primitive group”; the other settled in Dhenkanal and practising normal Indian agriculture, called here “advanced group”.

From the migration matrix the mean coefficient of kinship in a population subdivided by geographically restricted clans is estimated to be 0·0045 for the primitive group and 0·0324 for the advanced group. These values correspond to Alpine and Micronesian isolates, respectively. Estimates from genealogies of randomly paired sibships are substantially smaller (0·0016 and 0·0131, respectively), but are biased downward by incompleteness of pedigrees and by neglect of restricted migration within each group. Therefore the estimates from the migration matrix are presumably more reliable in this material, and perhaps commonly in tribal populations.     

Heterogeneity of long-distance migration in studies of genetic structure

One of the assumptions of migration matrix methods of population structure is that long-distance migrants are all sampled from a genetically homogeneous 'outside world'. This assumption has not often been tested. This paper examines migration and surname data from four towns in historical Massachusetts in order to examine this assumption and potential genetic effects of heterogeneous long-distance migration. Analysis of migration data shows that the rate of long-distance migration is significantly different for the four towns. The distributions of source populations for long-distance migrants into each town are significantly different. Surname analysis shows that in spite of the violation of the assumption of long-distance migrant homogeneity, there is little effect on the degree and pattern of within-group and among-group variation for these towns. This lack of effect seems related to genetic homogeneity of the long distance migrants.     

Genetic diversity of the IL-4, IL-4 receptor and IL-13 loci in mestizos in the general population and in patients with asthma from three subpopulations in Mexico

Asthma is an inflammatory airway disease characterized by increased serum IgE levels, mucus hypersecretion and infiltration of inflammatory cells, and is a multifactorial disease that exhibits genetic heterogeneity. Polymorphisms in the interleukin-4 (C-590T), interleukin-4 receptor (ile50val and gln576arg), and interleukin-13 (arg130gln) genes have been described as susceptibility alleles for asthma. This study was designed to determine whether asthma susceptibility is influenced by genotypic and allelic distribution of the above polymorphisms in three Mexican subpopulations. Four hundred and thirty-seven subjects from three Mexican subpopulations were classified into two groups: general population and affected/unaffected and genotyped for the above polymorphisms. We compared the distributions of the loci in the groups. In addition, we undertook association analysis between these loci and asthma phenotype in each affected/unaffected group, and determined Nei's genetic distance between the three subpopulations. The allelic and genotypic distributions of the polymorphisms differed between the three subpopulations. There was no association between any of the polymorphisms and asthma phenotype. However, there was a differential distribution of haplogroups (P < 0.0001) between the affected and the unaffected groups from the subpopulations of Jalisco and Guerrero. The genetic distribution of the four polymorphisms in the subpopulations did not influence susceptibility to asthma. Furthermore, the difference in the prevalence of asthma in these subpopulations is not attributable to the genetic background for the four polymorphisms analysed. However, haplogroup analysis suggests that the interaction of the polymorphisms and other predisposing alleles leads to the expression of the clinical phenotype.     

Multilocus enzyme electrophoresis analysis of Aspergillus fumigatus strains isolated from the first clinical sample from patients with invasive aspergillosis. EBGA Network. European Research Group on Biotype and Genotype of Aspergillus

The genotypes of 50 isolates of Aspergillus fumigatus from 11 patients with invasive aspergillosis, obtained from three hospitals in different geographical areas, were determined by multilocus enzyme electrophoresis (MLEE). The study analysed the genetic polymorphism of multiple isolates from the first sample. Seven of the 14 enzymic loci studied were polymorphic, giving rise to eight different electrophoretic types. For nine of 11 patients studied, no polymorphism was observed in isolates within the first clinical sample. Analysis of genetic distance between electrophoretic types demonstrated a genetic heterogeneity within each geographical site. Moreover, some genotypes were preferentially found in a given area and this revealed a population structure within these geographical sites. Therefore, the epidemiology of A. fumigatus should be considered separately for each of these areas. The multiple discriminatory markers of MLEE seem to provide a powerful tool for increasing the understanding of the biology of this fungus.     

Population structure of the rural communities on the island of Krk (Croatia): A comparison of genetic,cultural, and geographic data

The population structure of seven rural communities from the island of Krk (Croatia) was studied on the basis of its genetic constitution and genetic structure, and different sets of biological (genetic), biocultural (migration), cultural (linguistic), and geographic data. Genetic constitution was estimated from the allelic frequencies of nine tetranucleotide STR loci, three HLA class I loci, five HLA class II loci, and five red blood cell enzyme and serum protein loci. Genetic structure was based on coefficients of genetic diversity G_ST and genetic kinship R_ST. Population structure was assessed by the structure of mutual relationships among biological, biocultural, cultural, and geographic matrices through Mantel's test, or by relationships among biological, biocultural, cultural measures of distance and/or similarity, and geographic distance with regression analysis of the “isolation by distance” model. One group of genetic markers (red blood enzymes, serum proteins, and HLA polymorphisms) reflects heterogeneity of the rural communities (a reflection of important historical processes and migration patterns), and a second group of genetic markers (STR polymorphisms) reflects the currently observed genetic homogeneity of the rural population. The positive correlations between the matrices of genetic (HLA) and linguistic distances indicate their possible co-evolution under conditions of genetic isolation (low gene flow). Furthermore, the negative correlations between the matrices of genetic (STR) distances and the migration kinship of the second and the third cohort indicate temporal coincidence between genetic constitution and structure assessed from STRs and migration patterns in the period between 1892 and 1940. Finally, the positive correlations between the matrices of genetic (STR) and geographic distances indicate isolation by distance. Am. J. Hum. Biol. 12:509–525, 2000. © 2000 Wiley-Liss, Inc.     

Isonymic structure of the Argentine Northwest

Surname distribution may be used as a substitute for quantitative information on the genetic structure of human populations due to panmictic deviations. This study analysed the isonymic structure of the Argentine Northwest (ANW) populations. Surname distribution of 2,576,548 voters (year 2001) in the 117 departments of the region was analysed. Fisher's alpha and coefficient of random relationship by isonymy were estimated. A dendrogram of the 117 departments was constructed from the matrix of Euclidean distances. In general, alpha values found were lower than country averages, while kinship values were higher. Ten clusters were identified showing a spatial distribution closely related to geographic characteristics, means of communication, and location of economic activities of the region. The resulting pattern could be basically characterized by grouping the departments into two large clusters: (a) Those located in the centre of the region, which include the provincial capitals, presented greater diversity of surnames and a lower degree of kinship. (b) Those located in the regional periphery showed greater isolation and kinship. Isonymic parameters estimated agree with the demographic characteristics of populations, historical antecedents of population settlement and ANW geographic features.     

Murine mesenchymal stem cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration

Mesenchymal stem cells (MSCs) have demonstrated efficacy as cellular vectors for treating a variety of nervous system disorders. Nevertheless, few studies have quantified MSC engraftment levels or explored the mechanisms that promote their survival and migration in nervous tissue. In this study, we compared the engraftment kinetics and anatomical distribution of murine, male MSCs injected intracranially into neonatal versus adult female mice using a real-time PCR assay that targets the mouse SRY gene. These analyses revealed that MSCs exhibited low but equivalent engraftment levels in the central nervous system (CNS) of neonatal and adult transplant recipients at 12 days post-injection. However, MSC engraftment levels were significantly greater at 60 and 150 days post-transplantation in neonates as compared to adults. Despite these differences, engrafted MSCs were widely distributed along the neuraxis of the CNS in both transplant groups. Collectively, these data indicate that proliferation, but not engraftment and migration, of MSCs in brain are regulated by the host microenvironment. Using a genomics approach, we also identified MSC subpopulations that express neural adhesion proteins and receptors that regulate neuronal cell migration in brain, including cadherin 2, neurexin 1, ninjurin 1, neogenin 1, neuropilin 2, and roundabout homolog 1 and 4. Functional studies indicate these proteins confer cell adhesion and migration of MSCs in response to the appropriate chemoattractant. On the basis of these findings, we conclude that the unique molecular composition of MSC subpopulations imparts to them an inherent capacity to engraft and migrate in brain. These subpopulations may represent more potent cellular vectors for treating CNS disorders.     

Genetic variability and evolution of broad bean wilt virus 1: role of recombination,selection and gene flow

Analysis of four genomic regions from 37 geographically diverse isolates of broad bean wilt virus 1 (BBWV-1) showed high genetic diversity in comparison to most plant viruses. Comparison of synonymous and nonsynonymous substitutions of the small coat protein gene (SCP) revealed negative selection for most amino acid positions. Phylogenetic analysis of SCP showed that some BBWV-1 isolates from distant geographical areas were genetically close, suggesting long-distance migration. Analysis of genetic differentiation revealed high gene flow between Spanish and Near Eastern subpopulations, which were separated from North-Central and South-Eastern European subpopulations. Finally, putative recombinant and reassortant genomes were also identified.     

Kinship structures and migration in the Po Delta

The kinship analysis of seven genetic systems in the province of Ferrara permits some considerations on the possible chronology of emergence of their polymorphisms in the area. It is proposed that, assuming neutrality of these systems, and under several restrictions, the emergence by migration of the polymorphisms in the seven systems ACP, ESD, GLO, GPT, PGD, PGM_1; PGP might have had the following sequence: PGP and GLO and possibly PGD; PGMj and GPT; ACP and ESD. All polymorphisms must be older than the β-thalassemia polymorphism in the area.     

Expression of chemokine receptors CXCR4, CXCR5 and CCR7 on B and T lymphocytes from patients with primary antibody deficiency

The interaction of chemokines and their receptors directs lymphocyte migration, and is involved in the distribution and organization of lymphocytes within lymphoid tissues. We reasoned that abnormal chemokine receptor expression might give rise to defects of lymphocyte migration into and within lymphoid tissues, and consequently be associated with defective antibody production in primary antibody deficiencies. In this study, we have investigated the expression of chemokine receptors CXCR4, CXCR5 and CCR7 on lymphocyte subpopulations (naive and memory B cells; CD4⁺ and CD8⁺ T cells) in a cohort of patients with primary antibody deficiency (n = 23), and compared these with a group of healthy controls (n = 19). We show that there were significant differences in both the proportions of lymphocytes expressing, and the levels of expression of, specific chemokine receptors on individual lymphocyte subpopulations between patients and controls. Furthermore, these changes appeared more pronounced in patients with more severe antibody deficiency. These data support the hypothesis that abnormal lymphocyte trafficking may be involved in the pathogenesis of primary antibody deficiencies.     

Predicting admission rates to secure forensic psychiatry services

BACKGROUND: The planning and development of secure forensic psychiatry services for mentally disordered offenders in England and Wales has proceeded independently within different regional areas. However, certain mental disorders, offenders, and offending behaviour are all more prevalent in geographical areas characterized by socio-economic deprivation and social disorganization. Failure to consider these factors has led to inadequate service provision in some areas and inequity in funding. A new model is required to predict admissions to these services as an aid to resource allocation. METHOD: Actual admissions (N = 3155) to high and medium secure psychiatric services for seven of 14 (pre-reorganization) Regional Health Authorities, 1988-94. Expected admissions were calculated for each district using 1991 census data adjusted for under-enumeration. Standardized psychiatric admission ratios were calculated and a range of social, health status, and service provision data were used as explanatory variables in a regression analysis to determine variation between districts. RESULTS: Actual psychiatric admissions varied from 160% above to 62% below expected for age, sex, and marital status, according to patients' catchment area of origin, measured according to deciles of the distribution of underprivileged area scores at ward level. The most powerful explanatory variables included a composite measure of social deprivation, ethnicity and availability of low secure beds at regional level. CONCLUSION: Admission rates to secure forensic psychiatry services demonstrate a linear correlation with measures of socio-economic deprivation in patients catchment area of origin. A model was developed to predict admissions from District Health Authorities and is recommended for future use in resource allocation. Identification of factors that explain higher admission rates of serious offenders with mental disorder from deprived areas is a priority for future research.     

Genetic structure of the Utah Mormons: A comparison of kinship estimates from DNA blood groups,genealogies, and ancestral arrays

Kinship estimates based on shared proportions of European ancestry are constructed for 284 Utah males born in eight geographic subdivisions. These “ancestral kinship” estimates are compared with kinship coefficients based on DNA polymorphisms, blood groups, genealogies, isonymy, and migration matrices. At the subdivision level, a high correlation is observed between ancestral kinship and kinship based on isonymy. Comparing individuals, a significant correlation is obtained between ancestral kinship and genealogy derived kinship. Kinship estimates based on DNA and blood groups do not correlate significantly with ancestral kinship. This is most likely due to the effects of several generations of random mating in this population. © 1996 Wiley-Liss, Inc.     

Small-diameter porous poly (epsilon-caprolactone) films enhance adhesion and growth of human cultured epidermal keratinocyte and dermal fibroblast cells

Autologous keratinocyte grafts provide clinical benefit by rapidly covering wounded areas, but they are fragile. We therefore developed biocompatible hexagonal-packed porous films with uniform, circular pore sizes to support human keratinocytes and fibroblasts. Cells were cultured on these porous poly (epsilon-calprolactone) films with pore sizes ranging from novel ultra-small 3 microm to 20 microm. These were compared with flat (pore-less) films. Cell growth rates, adhesion, migration, and ultrastructural morphology were examined. Human keratinocytes and fibroblasts attached to all films. Furthermore, small-pore (3-5 microm) films showed the highest levels of cell adhesion and survival and prevented migration into the pores and opposing film surface. Keratinocyte migration over small-pore film surface was inhibited. Keratinocytes optimally attached to 3-microm-pore films due to a combination of greater pore numbers (porosity), a greater circumference of the pore edge per unit surface area, and greater frequency of flat surface areas for attachment, allowing better cell-substrate and cell-cell attachment and growth. The 3-microm pore size allowed cell-cell communication, together with diffusion of soluble nutrients and factors from the culture medium or wound substrate. These characteristics are considered important in developing grafts for use in the treatment of human skin wounds.