The prevalence of consanguineous marriages in an underserved area in Lebanon and its association with congenital anomalies

Background: Consanguinity is a recognized common practice among marriages in the Middle East. Many studies have suggested a strong association between first cousin marriages and the incidence of autosomal recessive diseases and congenital anomalies. The objectives of this study were to study the prevalence of consanguinity among the marriages of Bekaa (a region in Lebanon) with its sociodemographic correlates, and to assess the prevalence of congenital anomalies associated with these marriages. Methods: This study was a cross-sectional study done in three of the major areas of the Bekaa region. The sample size consisted of 552 households chosen based on proportionate random sampling according to population size in each area. The survey was conducted based on face-to-face interview with a member of the couples of each household. Results: The overall prevalence of consanguineous marriages was reported to be 42% with first cousin marriage constituting around 31% of the total marriages. No association was found between different socioeconomic status (SES) correlates and first cousin marriages. Results showed a significant association between first cousin marriage and mental retardation, physical retardation, bilateral cleft lip +/- cleft palate, cystic fibrosis, and congenital blindness. Conclusion: In a population with a high degree of inbreeding, the formulation of a public health program with multiapproach strategy, including education about the anticipated genetic consequences, prenatal diagnosis, neonatal screening, and genetic counseling, is a necessity.     

白化病的遗传流行病学研究

本文应用分离分析和血缘分析方法,对山东省１００余万人群遗传病调查中发现的３７个白化病核心家系进行了分析。结果表明：白化病存在遗传异质性,为多基因常染色体隐性遗传,最小基因数为８,平均基因频率为０．００２３,群体中致病基因携带者频率为０．０３８３;近亲结婚大大提高白化病的患病率。     

Incidence in Italy, genetic heterogeneity, and segregation analysis of cystic fibrosis

Taking advantage of the availability of an archive of consanguineous marriages that gives accurate estimates of consanguinity in Italy, it has been possible to calculate the increase of first- and second-cousin marriages among 624 couples of cystic fibrosis (CF) parents over the general population. From these estimates, the incidence of CF in Italy has been found to correspond approximately to 1/2,000. In turn, the same data have been used to test the hypothesis of genetic heterogeneity of CF, recently proposed, which is based on the presence of two distinct genetic disorders having similar frequencies. If such a hypothesis were true, the number of first-cousin marriages among CF parents should be significantly higher than that observed in our present study. Finally, the segregation analysis of 624 CF sibships has yielded under multiple selection a segregation ratio of 0.252, confirming the recessive mode of inheritance.     

Trends of consanguineous marriages in a Sunni Muslim population of West Bengal, India

The Muslim population of the Chaltaberia village in the district of South 24 Parganas in West Bengal is divided into several wards (paras) inhabited by people of specific surnames. The frequency of endogamous marriages within surnames is greater than randomly expected ones. An incomplete reproductive isolation is observed among the five dominant surnames. Consanguineous marriages occur more often outside the village than inside. Leaving out marriages between long distances, a small median distance of 6.36 km is recorded. The neighborhood area works up to be 552.2 km2, which is rather small. There is an underlying process of breeding isolation by distance. A generation length of 21 years has been used for examining the temporal change in consanguineous marriages and inbreeding, which generally appears to increase. There is a general trend of decline in consanguineous marriages towards the southern part of West Bengal and eastern part of Assam among the Bengalee Muslims. The frequency of consanguineous marriages is 7.3% out of all marriages (N=1153) that have taken place in six generations in the population. The first cousin marriage is nearly 50% of all marriages. Patrilineal marriages are common in marriages between second and third cousins. An increase of consanguineous marriages in the younger generation was observed, but the total frequency agrees with a general trend of a decline in the frequency of consanguineous marriages among the Muslims in this part of India.     

Inbreeding

Abstract

Data on inbreeding in several contemporary human populations are compared, showing the highest local rates of inbreeding to be in Brazil, Japan, India, and Israel. American populations are noteworthy for their extremely low inbreeding rates, with the mean frequency of first cousin marriages in the United States probably lower than 0.1 per cent. Some localities in Puerto Rico and Sweden show inbreeding levels half‐way between the extremes found in Brazil and Japan and in the United States. For European countries, Denmark, France, Italy, and North Ireland have a mean frequency of first cousin marriages of less than 1 per cent, while England, Wales, Germany, and Holland have a frequency probably lower than 0.5 per cent. The frequency of first cousin marriages in Portugal may lie between 1 and 2 per cent.     

Distribution of the incidence of anencephaly in Japan

Abstract

Distributions of the incidence of anencephaly in Japan were obtained using nationwide data on fetal and postnatal deaths of individuals with anencephaly during 1969–71. Higher incidences of anencephaly occurred in the urbanized and industrialized areas and lower values in the comparatively sparsely populated highlands. Population size and variance of incidence show a negative association. The distribution of the incidence seems to be binomial, and expected incidences based on binomial distribution indicated good agreement with weighted mean incidences in populations with different sizes. The rate of first cousin marriages among the parents of anencephalic patients is 1.86 per cent, a value not significantly different from the value of general population, 2.13 per cent. It seems that the inheritance of anencephaly is not related to a specific number of recessive genes.     

Incidence of Friedreich ataxia in Italy estimated from consanguineous marriages

The frequency of consanguineous marriages up to second-cousin degree has been carefully established in the past for each of the 95 Italian provinces using the Archive of about 500,000 dispensations given by the Catholic church for such marriages over a 55-year period. It has therefore been possible to compare the frequency of consanguineous marriages observed among 83 couples of parents of Friedreich patients with the frequency of consanguineous marriages of the same degree in the different Italian provinces during the same years. From these data, an estimate of the incidence of the disease has been obtained for the whole nation (between 1/22,000 and 1/25,000). In Southern Italy, where 16 out of the 18 consanguineous marriages among Friedreich parents are concentrated, the incidence of the disease is similar (between 1/25,000 and 1/28,000). This study indicates that the Archive of consanguinity existing in Italy allows a reliable comparison of the frequency of consanguineous marriages among parents of patients with that of the general population. The same method can therefore be applied to the study of incidence of other autosomal recessive disorders in Italy.     

Risikoberechnungen beim autosomal-rezessiven Erbgang

Genetic risk calculations are demonstrated for autosomal recessive diseases using Bayesian calculation tables. The Hardy-Weinberg law forms an important basis for the determination of a priori probabilities. We demonstrate how healthy relatives, molecular test results and complex genetic models affect the risk. Examples of autosomal recessive inheritance with cystic fibrosis (CF) and infantile spinal muscular atrophy (SMA) have been selected.     

Prevalence and sociodemographic correlates of consanguineous marriages in Turkey

The aim of this study was to determine the prevalence and sociodemographic correlates of consanguineous marriages in Turkey using data derived from the 2003 Turkey Demographic and Health Survey (TDHS-2003). Demographic surveys conducted in the last 40 years consistently show that Turkey is a country with a high level of consanguinity. In the latest demographic survey (TDHS-2003), a nationally representative sample of 8075 ever-married women, consanguineous marriages accounted for 22% of the total, which is equivalent to a mean coefficient of inbreeding (alpha) of 0.011. There are changing secular profiles in the rates of consanguinity in general and of the specific sub-types of cousin marriages in particular in Turkey. The prevalence of first cousin marriages among all consanguineous marriages presents a steady decline from one marriage cohort to the next. The changes observed over time may be attributable to several factors such as the increase in educational level of women, the nuclearization of the family system, the mobility from rural to urban settings, a better socioeconomic status of families, an increase in women's labour force participation in formal sectors, lower fertility rates resulting in a smaller number of cousins available for marriage, and an increased awareness of the effects of consanguineous unions on child health in cases where there is an inherited recessive disease in the family. Any attempts to discourage consanguinity at the population level appear to be inappropriate and undesirable, especially when the consanguineous union remains an integral part of the cultural and social life of Turkey. Nevertheless the WHO-recommended approach to minimizing the negative effects of consanguinity on child health should be followed, i.e. the identification of families with a high risk of a genetic disease and the provision of prospective genetic counselling.     

Consanguineous marriages in the population of Sheikhupura (Punjab), Pakistan

This study was based on 1007 couples from the Sheikhupura population. The proportions of various parental relationships were: 0.3784 1st cousins, 0.0318 1st cousins once removed, 0.0784 double 2nd cousins, 0.1033 bradari distant relations, 0.3416 bradari, and 0.0665 unrelated parents. Mean paternal ages in unrelated couples are significantly higher than in 1st cousins, double 2nd cousins, and bradari relations. The differences in paternal and maternal ages are significantly higher in unrelated relations as compared to 1st cousins and double 2nd cousins. Procounced effects of consanguinity on parental deaths and neonatal deaths were observed in 1st cousin marriages compared to other relationships. Juvenile and infant deaths show comparatively less effects of consanguinity in 1st cousin marriages. Mean coefficient of inbreeding calculated for this population was 0.0271. Lethal gene equivalents calculated were 1.5424. The added risk of affected children in 1st cousins over that of unrelated parents was 4.82%. The results suggest that the deleterious genes show their effects more in the prenatal than in the postnatal period.     

A low prevalence of cystic fibrosis in Uruguayans of mainly European descent

Cystic fibrosis is the most common hereditary disease in populations of European descent, with its prevalence depending on the populations and ethnic groups studied. In contrast to Europe and North America, there is little information about this disease in Latin America. Uruguay currently has a human population of 3,000,000, with a low rate of miscegenation and no remaining isolated Amerindian groups. In the present study, we estimated the prevalence of cystic fibrosis in this country based on the detection of DeltaF508 mutation carriers in 500 unrelated individuals and on the frequency of individuals homozygous for this mutation within the affected population. The latter was calculated from the frequency of the different mutations and genotypes observed in a sample of 52 previously described patients with confirmed cystic fibrosis. A theoretical estimate of the prevalence of cystic fibrosis based on anthropological data suggested a frequency of 25 affected individuals/100,000 inhabitants. However, our data indicated that the true prevalence in the population was considerably lower (6.9 cases/100,000 inhabitants).     

Low frequency of the deltaAF508 mutation of the CFTR gene in a highly admixed population in Bahia, Brazil

Cystic fibrosis (CF) is the most common autosomal recessive disease in the European (Caucasian) population, with an incidence of 1:2000 to 1:8000. The deltaF508 mutation (66%) is predominant among more than 1300 different mutations of the CFTR gene. The population of the state of Bahia, in northeastern Brazil, is highly admixed (mainly African and Portuguese descendants), and so far, no study has been carried out to assess the molecular basis of CF in this population. We determined the deltaF508 mutation frequency in 503 individuals from the general population of Salvador, the capital of the state of Bahia, and in 144 CF patients from several cities in Bahia. In the general population samples we found 4 individuals heterozygous for the deltaF508 mutation (allele frequency of 0.4%). This frequency was lower than that found in the state of Rio de Janeiro, in southeastern Brazil, and similar to that reported for the state of Paraná, in the far south. In the CF patients we found 9 heterozygous individuals and 8 homozygous individuals (allele frequency of 8.68%) for the deltaF508 mutation. This frequency is considerably lower than the average frequency of CF in the world population and in the Brazilian CF population of European ancestry (47%). These data could be explained by the intense admixture among the population in Bahia, and they suggest a heterogeneous molecular basis for CF in this area of Brazil.     

Allele frequency for Cystic fibrosis in Indians vis-a/-vis global populations

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This gene encodes a protein involved in epithelial anion channel. Cystic fibrosis is the most common life-limiting genetic disorder in Caucasians; it also affects other ethnic groups like the Blacks and the Native Americans. Cystic fibrosis is considered to be rare among individuals from the Indian subcontinent. We analyzed a total of 29 world׳s populations for cystic fibrosis on the basis of gene frequency and heterozygosity. Among 29 countries Switzerland revealed the highest gene frequency and heterozygosity for CF (0.022, 0.043) whereas Japan recorded the lowest values (0.002, 0.004) followed by India (0.004, 0.008). Our analysis suggests that the prevalence of cystic fibrosis is very low in India.     

Consanguineous marriages in Afghanistan

The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Afghanistan populations. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 7140 from the following provinces: Badakhshan, Baghlan, Balkh, Bamyan, Kabul, Kunduz, Samangan and Takhar. Consanguineous marriages were classified by the degree of relationship between couples: double first cousins, first cousins, first cousins once removed, second cousins and beyond second cousins. The coefficient of inbreeding (F) was calculated for each couple and the mean coefficient of inbreeding (α) estimated for each population. The proportion of consanguineous marriages in the country was 46.2%, ranging from 38.2% in Kabul province to 51.2% in Bamyan province. The equivalent mean inbreeding coefficient (α) was 0.0277, and ranged from 0.0221 to 0.0293 in these two regions. There were significant differences between provinces for frequencies of different types of marriages (p<0.001). First cousin marriages (27.8%) were the most common type of consanguineous marriages, followed by double first cousin (6.9%), second cousin (5.8%), beyond second cousin (3.9%) and first cousin once removed (1.8%). There were significant differences between ethnic groups for the types of marriages (χ2=177.6, df=25, p<0.001). Tajiks (Soni) and Turkmens (also Pashtuns) showed the lowest (α=0.0250) and highest (α=0.0297) mean inbreeding coefficients, respectively, among the ethnic groups in Afghanistan. The study shows that Afghanistan's populations, like other Islamic populations, have a high level of consanguinity.     

Inbreeding in Southeastern Spain

In this paper, the structure of a southeastern Spanish population was studied for the first time with respect to its inbreeding patterns and its relationship with demographic and geographic factors. Data on consanguineous marriages (up to second cousins) from 1900 to 1969 were taken from ecclesiastic dispensations. Our results confirm that the patterns and trends of inbreeding in the study area are consistent with those previously observed in most non-Cantabrian Spanish populations. The rate of consanguineous marriages was apparently stable between 1900 and 1935 and then sharply decreased since 1940, which coincides with industrialization in Spain. A marked departure from Hardy-Weinberg expectations (0.25) in the ratio of first cousin (M22) to second cousin (M33) marriages in the study population (0.88) was observed. The high levels of endogamy (>80%) and its significant steadiness throughout the twentieth century is noteworthy. Accordingly, our results show that exogamous marriages were not only poorly represented but also that this reduced mobility (<6 km) suggests that the choice of a mate was preferentially local. We found higher mobility in M22 with respect to M33 cousin mating. The relationships between population size and consanguinity rates and inbreeding fit power-law distributions. A significant positive correlation was observed between inbreeding and elevation. Many Spanish populations have experienced a prolonged and considerable isolation across generations, which has led to high proportions of historical and local endogamy that is associated, in general, with high \( \overline{F} \) values. Thus, assessing genomic inbreeding using runs of homozygosity (ROH) in current Spanish populations could be an additional pertinent strategy for obtaining a more refined perspective regarding the population history inferred from the extent and frequency of ROH regions.     

Frequency of consanguineous marriages among parents and grandparents of Down patients

Summary The existence of a rare autosomal gene which in the homozygous state would cause mitotic nondisjunction in the Down zygote has been hypothesized in the past by Alfi et al. (1980). This hypothesis can be supported or contradicted by the study of the frequency of consanguineous marriages among parents of affected children. Our study on 242 children affected with Down syndrome does not show any increase in the frequency of consanguineous marriages among their parents with respect to the general population, and therefore does not support the hypothesis of an autosomal gene controlling mitotic nondisjunction. Our data do not show any increase in the frequency of consanguineaous marriages even among paternal and maternal grandparents of the affected children, thus not supporting the other possible explanation of an autosomal recessive condition in one of the patient's parents which would cause meiotic nondisjunction.     

Consanguineous marriages in Beirut: Time trends,spatial distribution

Abstract

Twenty‐five per cent of all marriages are consanguineous in a population‐based sample of couples from Beirut. Marriages between distant relatives decline with time, while first‐cousin marriages remain relatively stable. Among first‐cousin marriages, the proportions of father's brother's daughter marriages (37 per cent) and of patrilateral unions (48 per cent) are particularly low. A spatial representation demonstrates an uneven distribution of consanguineous marriages, and an association of high levels of endogamy with Muslim religion, low educational level, and low occupational status.     

Heredity of progressive muscular dystrophy: Reflections on a case study

Abstract

Data on the prevalence of divorce and separation among parents of children with cystic fibrosis and other chronic diseases indicate that marital breakdown is no more prevalent among these couples than it is in a general population. For couples who attended genetic counseling clinics or had children with spina bifida or leukemia, the divorce rate is lower than the United States national average. For parents of children with cystic fibrosis, the divorce rate is the same as the national average. The high recurrence risk for cystic fibrosis may deter many parents from further reproduction. We speculate that the inability to plan more children may be the factor responsible for the higher prevalence of divorce among these parents compared to those of children with other chronic diseases.     

Genetically modified pigs to model human diseases

Genetically modified mice are powerful tools to investigate the molecular basis of many human diseases. Mice are, however, of limited value for preclinical studies, because they differ significantly from humans in size, general physiology, anatomy and lifespan. Considerable efforts are, thus, being made to develop alternative animal models for a range of human diseases. These promise powerful new resources that will aid the development of new diagnostics, medicines and medical procedures. Here, we provide a comprehensive review of genetically modified porcine models described in the scientific literature: various cancers, cystic fibrosis, Duchenne muscular dystrophy, autosomal polycystic kidney disease, Huntington’s disease, spinal muscular atrophy, haemophilia A, X-linked severe combined immunodeficiency, retinitis pigmentosa, Stargardt disease, Alzheimer’s disease, various forms of diabetes mellitus and cardiovascular diseases.     

Inbreeding patterns in La Cabrera, Spain: dispensations, multiple consanguinity analysis, and isonymy

Marital structure and inbreeding coefficients were analyzed in La Cabrera, an isolated mountain region in northwestern Spain. A total of 5,714 marriages were celebrated from 1880 to 1989 in the 37 parishes of the area. The total frequency of consanguineous marriages (up to the fourth degree) is 23.05%; multiple consanguineous marriages are remarkably common, reaching 5.43% of the total. The first cousin/second cousin ratio (referred to as kinship-type frequencies) is 0.43. The inbreeding values are the highest recorded in Spain and in Europe: alpha3 is 4.82 x 10(-3) for the whole period and alpha4 is 6.78 x 10(-3) for 1880--1919. The temporal trend of inbreeding shows high values (alpha3 > 4.5 x 10(-3)) for a particularly long period (1900--1959) and a rapid decline from 1960 onward. This historical inbreeding trend is clearly related to changes in population size. The frequencies of multiple consanguineous marriages and the analysis of isonymy show that the inbreeding structure is related to geographic and demographic factors. Comparing the results at two hierarchical levels (La Cabrera as a whole and the 37 parishes individually), we conclude that the inbreeding values are affected by internal geographic subdivision of the population (Wahlund effect). Social and cultural factors, such as avoidance of or preference for consanguineous marriages, are less important but depend on the kinship type involved.