The Effect of Inbreeding on Mortality and Morbidity among Telugu-speaking Populations of Kharagpur, West Bengal, India

Increased mortality and morbidity including congenital malformations among the offspring of consanguineous marriages have been widely reported in human populations from different parts of the world. However, there are few studies on the effect of the intensity of inbreeding and different degrees of inbreeding on mortality and morbidity. The present study is an attempt to examine the effects of inbreeding on mortality and morbidity including congenital disorders in different levels of inbreeding among Telugu-speaking populations of Kharagpur, West Bengal, India, based on data collected through extensive pedigrees. The study reveals that the frequency of spontaneous abortions and stillbirths is higher in the offspring of consanguineous marriages than in that of non-consanguineous marriages. A similar effect is also observed in the infant mortality rate, which is known to have a genetic component, but is not seen in the mortality rate of children and juveniles. The rate of morbidity is consistently higher in the offspring of consanguineous marriages with a sex bias in favour of inbred females. The increased morbidity rates in inbred individuals tend to be inversely correlated with the increase in average autosomal inbreeding coefficient. This appears to strengthen Sanghvi’s hypothesis of a decline in the frequency of deleterious genes with intensification of inbreeding through generations. The present study also confirms an increase in genetic disorders with an increase in inbreeding in almost all populations.     

Isolation and marriage patterns in four South Tyrolean villages (Italy) during the nineteenth century

No information is currently available on the marriage patterns of German-speaking communities of the South Tyrol area. The aim of this study is to investigate the reproductive isolation of four South Tyrolean mountain villages during the 19th century. Data about 3953 marriages were drawn from existing pedigrees and completed with data from the parish registers of the studied villages to calculate the following indicators: age at marriage, endogamy, inbreeding from dispensations and from isonymy and repeated pairs of surnames among couples. The results show high levels of endogamy (78-87%) and an elevated age at marriage in all the studied villages. The percentages of consanguineous marriages (10-33%) vary considerably but result overall in relatively low inbreeding values (alpha 0.0015-0.0036; Ft 0.0098-0.0138). Levels of endogamy are consistent with the geographic characteristics of the area, while inbreeding values are lower than those observed in previous studies on Alpine communities. This is due to a low frequency of marriages between close relatives, probably related to the peculiar demographic and cultural characteristics of the studied populations that differentiate them from neighbouring Italian-speaking villages.     

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.     

Note on estimates of the inbreeding coefficient through study of pedigrees and isonymous marriages

Crow and Mange (1965) developed a method to estimate the inbreeding coefficient (F) through an ingenious surname analysis. Such formulations assume a regularity of transmission of surnames, monophyletism, and random occurrence of consanguineous marriages. Accordingly, the ratio of isonymous partners to F of the offspring is equal to 4. Nevertheless, genealogy analyses show that the consanguineous marriages do not necessarily occur regularly. Therefore the isonymy analysis gives a misestimation of the inbreeding coefficient, depending on the prevailing form of nonrandomness. We suggest a small correction to the formulation in situations when pedigree information is available. The weighted mean of the ratio of isonymous partners to F of the known consanguineous marriages is suggested as a way to improve the formulas. The technique was applied to a northeastern Brazilian sample, and the results agree well with those of bioassays and therefore provide an apparently more realistic estimate of the inbreeding coefficient by isonymy.     

Consanguinity and susceptibility to infectious diseases in humans

Studies of animal populations suggest that low genetic heterozygosity is an important risk factor for infection by a diverse range of pathogens, but relatively little research has looked to see whether similar patterns exist in humans. We have used microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increases risk of infection. Our results indicate that inbred individuals are more common among our infected cases for TB and hepatitis, but only in populations where consanguineous marriages are common. No effect was found either for leprosy, which is thought to be oligogenic, or for hepatitis in Italy where consanguineous marriages are rare. Our results suggest that consanguinity is an important risk factor in susceptibility to infectious diseases in humans.     

Socioeconomic, demographic and legal influences on consanguinity and kinship in northern coastal Sweden 1780-1899

Most studies on consanguinity have been conducted on contemporary populations and have focused on the prevalence and types of preferred intra-familial marriage. With its comprehensive birth, marriage and deaths records dating back to the late 17th century, and the legal bar on first cousin marriage removed in the mid-19th century, Sweden offers unique opportunities to examine the factors that determine by whom, where and why consanguineous marriages were contracted. The present study covers the period 1780-1899 and presents a detailed portrait of cousin and sibling exchange marriages in the Skellefte? region of northern coastal Sweden. The combined prevalence of first, second and third cousin marriage increased from 2.3% in 1790-1810 to 8.8% in 1880-1899, and multi-generation consanguinity also increased significantly over the study period. The distribution and prevalence of first cousin marriages was strikingly non-random, with a significantly greater propensity for consanguinity among land-owning families, especially involving first-born sons, within specific pedigrees, and in a number of more remote inland communities. Additional factors associated with a greater likelihood of consanguineous marriage included physical or mental disability among males, and among females the prior birth of an illegitimate child. Besides the inherent interest in the social and demographic structure of this region of northern Sweden during the course of the 19th century, in future studies it will be important to determine the degree to which the observed patterns of consanguineous and sibling exchange marriages in these past generations could have influenced present-day genetic structure.     

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.     

Parental consanguinity as a cause for increased incidence of births defects in a study of 238,942 consecutive births.

The risk for birth defects in the offspring of first-cousin matings has been estimated to increase sharply compared to non consanguineous marriages. As a general decline in the frequency of consanguineous marriages was observed in this century, one wonders whether consanguinity is still a factor in the appearance of birth defects in developed countries. Based on our registry of congenital anomalies we tried to answer to this question. In the population studied in North-Eastern France a consanguineous mating was known in 1.21% of the cases with congenital anomalies, vs. 0.27% in controls, (p < 0.001). The frequency of the malformations recorded paralleled the degree of consanguinity: out of 89 malformed children, 51 were seen in first-cousins mating (10.3 times more frequent than in offspring of non consanguineous couples), 17 in second-cousins marriages and 18 in more distant relatives mating. Three were uncle-niece marriage. Excluding known mendelian conditions these numbers were 73, 36, 17 and 17 respectively and the corresponding relative risk were 3.68, 3.01, 3.41 and 4.89 respectively. Therefore there is a negative dose-response effect between level of inbreeding and risk of congenital malformations. Consanguineous mothers were more often pregnant than non consanguineous mothers (p < 0.01) and they had more stillbirths than non consanguineous mothers. These results show that consanguinity is still a factor of birth defects and they must be taken into account for genetic counseling of inbred marriages, in developed countries.     

Quantification of homozygosity in consanguineous individuals with autosomal recessive disease

Individuals born of consanguineous union have segments of their genomes that are homozygous as a result of inheriting identical ancestral genomic segments through both parents. One consequence of this is an increased incidence of recessive disease within these sibships. Theoretical calculations predict that 6% (1/16) of the genome of a child of first cousins will be homozygous and that the average homozygous segment will be 20 cM in size. We assessed whether these predictions held true in populations that have preferred consanguineous marriage for many generations. We found that in individuals with a recessive disease whose parents were first cousins, on average, 11% of their genomes were homozygous (n = 38; range 5%-20%), with each individual bearing 20 homozygous segments exceeding 3 cM (n = 38; range of number of homozygous segments 7-32), and that the size of the homozygous segment associated with recessive disease was 26 cM (n = 100; range 5-70 cM). These data imply that prolonged parental inbreeding has led to a background level of homozygosity increased approximately 5% over and above that predicted by simple models of consanguinity. This has important clinical and research implications.     

Inbreeding and matrimonial structure in a Pyrenean community (Ansó, Huesca, Spain), 1712-1982

Using data from parish records from 1712 to 1982 in a Spanish Pyrenean village, Ansó, the effects of the raw nuptiality, the types of consanguineous marriages and the rate and evolution of inbreeding on the mating structure have been studied. This structure has been modified in the course of time mostly through the secular variations in the frequency of consanguineous marriages. Recent inbreeding decrease in Ansó is related to the population diminution and cultural changes associated with isolate breakdown.     

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.     

Inbreeding pattern and reproductive success in a rural community from Galicia (Spain)

The present paper is based on information on marital patterns and reproductive performance (reconstituted families) in the rural community of Los Nogales, Galicia, Spain. Biodemographic data were used to analyse temporal changes and structure of consanguinity in the population, as well as consanguinity versus reproductive success. Of 2347 marriages celebrated between 1871 and 1977, 5.15% were between relatives (up to third degree). The population's inbreeding coefficient was above the Spanish average after 1890, and levels were high during the first part of the 20th century. A possible underestimation of inbreeding coefficients is attributed to the elevated frequency of extramarital births occurring in the Los Nogales population (13.47%). The structures of consanguineous matings, expressed as C22/C33 and C33/C44, turned out to be 0.86 and 0.82 respectively. Regarding migration, before 1920 consanguinity increased, but net migration was negative. In the period 1920-1929 consanguinity began to decrease, prior to maximum emigration. As for reproductive success, information from 1503 reconstituted families shows that complete fertility was slightly higher among consanguineous families despite a greater infant mortality. Lower infertility in consanguineous matings, as well as lower age at marriage and first maternity, could explain the above results.     

The East Indian Diaspora in Costa Rica: Inbreeding Avoidance, Marriage Patterns, and Cultural Survival

Anthropologists have long been interested in the survival of Indian cultural traits in the New World. In this article, we present results of an ongoing project with a Costa Rican community that descends from East Indian indentured servants. We focus on the group's marriage patterns and how these patterns might have helped keep the community as a cohesive ethnic group. We investigate the group's level of inbreeding by computing the inbreeding coefficient using two different methods. We show that the community has been successful at keeping its inbreeding low, despite its small size, by allowing marriage with nonmembers of the community. We propose that unless consanguineous marriages are allowed virtually all of the community's marriages will be with noncommunity members. Absorption into tourism, as well as the community's staunch avoidance of consanguineous marriages and virtually universal marriage with noncommunity members, will likely contribute to their disappearance as a viable ethnic group.     

Medicogenetic study of isolates in Uzbekistan. I. Statement of the problem and characteristics of the groups studied]

The paper comprises results of studying some demographic and populaton characteristics of the inhabitans of the Samarkand region as a whole and two villages, Karakent and Ishan, inhabited with Uzbeks-Khoja, a special religious-social caste in the past. It is shown that 87.4% of marriages in the Samarkand region are of international character (the information has been obtained on 7995 married couples). The frequency of consanguineous marriages is 11.6%, and among them 40.5% are first-cousin marriages and 39.1% are marriages of remote relatives. The coefficients of inbreeding are rather high among the Jewish, Tajik and Uzbek communities. The coefficient of inbreeding as a whole is F=0.0042 in this region and approaches to the maximal level, characterizing a panmix population. The average size of a family in the villages of Karakent and Ishan is approximately 4.0 persons. The values of reproductive performance, the nature of termination of pregnancies do not differ from those of panmix population. The percentage of intravillage and consanguineous marriages are 56% and 12.5% for the first village, and 25% and 2% for the second one respectively. The coefficient of inbreeding for karakent is F=0.0064, for Ishan--F=0.0014. Taking into consideration the historical development of the two villages and the cumulative data, the conclusion is drawn that Karakent is an isolate on a religious ground whereas Ishan is a disintegrated isolate.     

新疆伊犁五个少数民族的近亲结婚

1983年4月至1984年5月,对新疆伊犁哈萨克自治州五个民族的近亲结婚情况进行了调查。调查的婚姻数为维吾尔2553起,哈萨克1079起,回1235起,锡伯1222起,蒙古446起。近亲结婚率与平均近交系数分别为:维吾尔——8.23％与 46.74×10~(-4),回——8.10％与45.07×10~(-4),锡伯——4.66％与24.93×10~(-4),哈萨克——2.87％与11.31×10~(-4)。蒙古——0.45％与 2.80×10~(-4)。解放以来,维吾尔族与回族的近亲结婚率有上升趋势,而锡伯族的则有下降趋势。各族近亲结婚中大部分为亲表亲结婚,但堂亲结婚在维吾尔族的近亲结婚中竟占26.18％,在回族中也占16.00％。1303名近亲结婚子女中的七岁前死亡率(12.89％)及先天性缺陷与遗传性疾病发生率(2.99％)显著高于6370名非近亲结婚子女的相应值(7.65％及0.38％)。     

Royal dynasties as human inbreeding laboratories: the Habsburgs

The European royal dynasties of the Early Modern Age provide a useful framework for human inbreeding research. In this article, consanguineous marriage, inbreeding depression and the purging of deleterious alleles within a consanguineous population are investigated in the Habsburgs, a royal dynasty with a long history of consanguinity over generations. Genealogical information from a number of historical sources was used to compute kinship and inbreeding coefficients for the Habsburgs. The marriages contracted by the Habsburgs from 1450 to 1750 presented an extremely high mean kinship (0.0628±0.009), which was the result of the matrimonial policy conducted by the dynasty to establish political alliances through marriage. A strong inbreeding depression for both infant and child survival was detected in the progeny of 71 Habsburg marriages in the period 1450–1800. The inbreeding load for child survival experienced a pronounced decrease from 3.98±0.87 in the period 1450–1600 to 0.93±0.62 in the period 1600–1800, but temporal changes in the inbreeding depression for infant survival were not detected. Such a reduction of inbreeding depression for child survival in a relatively small number of generations could be caused by elimination of deleterious alleles of a large effect according with predictions from purging models. The differential purging of the infant and child inbreeding loads suggest that the genetic basis of inbreeding depression was probably very different for infant and child survival in the Habsburg lineage. Our findings provide empirical support that human inbreeding depression for some fitness components might be purged by selection within consanguineous populations.     

Migration as a determinant of marriage pattern: preliminary report on consanguinity among Afghans

Two sample populations, one refugee and one resident, were studied. The frequencies of consanguineous marriages came out to be 49.8%and 55.4%, respectively, for the refugees and the residents. Caste endogamy was dominant both in the residents and the refugees. The mean coefficient of inbreeding was calculated to be 0.0303 for the refugee population and 0.0332 for the resident population samples. First cousin marriage was the dominant type of marriage in both samples; father's brother's daughter (FBD) marriage was more frequent among the refugees while mother's brother's daughter(MBD) marriage was more frequent among the residents. Education has no decreasing effect on the incidence of consanguineous marriages. A significant difference in the pattern of marriages in the refugees is observed after the Saur Revolution of 1979.     

Frequency of first-cousin marriages from civil marriage certificates in Argentina

In Argentina information concerning relatedness of mates, especially first cousins, was introduced into the legal marriage certificate, record, and statistical report in 1968. The 1980-1981 biennial data, including 212,320 legal marriage reports, were analyzed for all of Argentina, subdivided into 22 states and 494 counties. The registered 0.373% of first-cousin marriages allows an estimate of consanguineous marriages of 0.629% and a mean inbreeding coefficient of alpha = 0.00031. This estimate lies between the observed alpha = 0.00011 from hospital births and alpha = 0.00052 from Roman Catholic Church dispensations. These differences are not large, and they may be due to sampling variations, indicating a low rate of inbreeding in Argentina. The frequency of first-cousin marriages in the 22 Argentine states is heterogenous, and 9 counties, representing 5 different regions, were identified as having a high rate of first-cousin marriage. Three of these were previously known as genetic isolates. A second series of data, including all 32,690 legal marriages registered in the state of Buenos Aires during the first half of 1984, showed a frequency of first-cousin marriages of 0.677%. First-cousin mates, compared with non-first-cousin mates, had a higher frequency of both mates being born in the same state of Buenos Aires and similar frequency distributions for age at marriage, single previous marriage status, level of education, and rate of unemployment. It is concluded that legal marriage data on consanguinity is reliable, inexpensive, universal, and enduring. The last two characteristics make them suitable for the survey of geographic clusters and time trends.     

Genetic subdivision of Dagestan ethnic populations

Relationships between ethnic and genetic differentiation with respect to 54 microsatellites have been analyzed in five Daghestan ethnic groups. To detect the microsatellites, human chromosomes 3, 17, and 18 were screened with a step of 10 cM (Weber/CHLC 9.0 markers) at the Mammalian Genotyping Service (National Institute of Health, United States). Comparison of the polymorphism of these loci in Daghestan populations with average worldwide data has revealed generally low heterozygosity in Daghestan populations, which is accounted for by traditional endogamous and consanguineous marriages throughout the history of these populations. The inbreeding coefficient in Daghestan ethnic groups varies from 0.005 to 0.0134 and is close to the worldwide maximum known to date. For some DNA loci, significant differences between the offsprings of consanguineous and exogamous marriages with respect to allele sizes and their variance have been found. The Daghestan ethnic populations studied differ from one another in both the frequencies of common alleles and the presence of rare alleles that are unique for each ethnic group of Daghestan and have not been found in any other population in the world.     

Genetic Subdivision of Daghestan Ethnic Populations

Relationships between ethnic and genetic differentiation with respect to 54 microsatellites have been analyzed in five Daghestan ethnic groups. To detect the microsatellites, human chromosomes 3, 17, and 18 were screened with a step of 10 cM (Weber/CHLC 9.0 markers) at the Mammalian Genotyping Service (National Institute of Health, United States). Comparison of the polymorphism of these loci in Daghestan populations with average worldwide data has revealed generally low heterozygosity in Daghestan populations, which is accounted for by traditional endogamous and consanguineous marriages throughout the history of these populations. The inbreeding coefficient in Daghestan ethnic groups varies from 0.005 to 0.0134 and is close to the worldwide maximum known to date. For some DNA loci, significant differences between the offsprings of consanguineous and exogamous marriages with respect to allele sizes and their variance have been found. The Daghestan ethnic populations studied differ from one another in both the frequencies of common alleles and the presence of rare alleles that are unique for each ethnic group of Daghestan and have not been found in any other population in the world.