The terms inbreeding and consanguinity are used to describe unions between couples known to share at least one common ancestor. While now rare in Western societies, marriages between close biological kin are preferential in many parts of the world, including North and sub-Saharan Africa, the Middle East, the Turkic- and Farsi-speaking countries of Central and South Asia, and much of the Indian subcontinent. Although the rates and types of inbred union may vary according to religious and societal norms, marriage between first cousins is especially common and in a country such as Pakistan accounts for over 50 percent of all marital unions. An incestuous relationship is a union between biological relatives that is closer than permissible under prevailing legislation. Most commonly, incest is defined as mating between first-degree relatives, i.e., fatherâ€“daughter, motherâ€“son, or brotherâ€“sister, who have 50 percent of their genes in common. However, in some countries the definition may be widened to include half-sib and uncleâ€“niece unions.
1. Human Inbreeding
Many examples of successful consanguineous unions are cited in the biblical texts, including the marriage of Abraham with Sarah his half-sister (Genesis 20:12), and Amram and Jochebed, the parents of Aaron and Moses who were nephew and aunt (Exodus 6:20). At a later date the permitted degrees of marital relationships were extensively defined, with marriages up to and including uncleâ€“niece permitted (Leviticus 18:7â€“18). These guidelines were generally adopted by the Protestant churches after the Reformation, although in most denominations the closest form of approved union has been between first cousins. For Roman Catholics, diocesan dispensation has been and remains a prerequisite for marriage between first cousins, and the Christian Orthodox church adopts a similarly proscriptive stance even with more remote relationships. Among the other major world religions, attitudes to close kin marriage are generally favorable or neutral in Buddhism, Confucianism, Islam, and Judaism. However, for the Aryan Hindus of North India, pedigrees are examined over the preceding seven generations for males and five generations for females to ensure avoidance of a consanguineous union.
1.1 Attitudinal Changes in the Response to Consanguineous Marriages
Prior to the mid-nineteenth century, first-cousin marriages were commonly contracted in many Western societies, including countries such as Spain and Italy where a large majority of the population was Roman Catholic. From the 1850s onward an often acrimonious debate commenced within the scientific and medical communities of North America and Western Europe into the biological effects of close kin marriage, with Charles Darwin, who had married his first cousin Emma Wedgwood, a leading protagonist (Bittles 1994). In Europe, and in most countries that had been colonies of the major European powers, this debate resulted in few if any legislative changes. However, within the USA the eventual outcome was the passage of laws at state level to control, and in many cases to ban, first-cousin unions, even though the information on which these laws were based frequently appeared to be more emotive than factual in nature. Michigan, New Jersey, and Ohio subsequently rescinded their prohibition on first-cousin marriages, but they remain illegal in twenty-two states and are a criminal offense in eight others (Bratt 1984, Ottenheimer 1990). Interestingly, the legislation passed by some individual states recognized the traditions of specific constituent communities and so, for example, uncleâ€“niece marriages (but not auntâ€“nephew) are permissible within the Jewish community of Rhode Island, while Native Americans in Colorado are free to marry their stepchildren.
1.2 Contemporary Societies in which Consanguineous Marriage is Preferential
As indicated in Sect. 1.1, the current legal situation in the USA differs markedly from that in many other parts of the world where consanguineous unions, a term derived from the Latin consanguinitas and indicating â€˜shared blood,â€™ are strongly preferential. The reasons for this preference are mainly social and economic in origin, and include the strengthening of family relationships and the maintenance of family property and land-holdings. Prenuptial arrangements also are greatly simplified, and the security of marrying a partner whose entire family background is known is perceived as a major benefit in ensuring both the initial success and the lasting stability of the union. Variation in the specific types of marriage contracted, e.g., with fatherâ€™s brotherâ€™s daughter first-cousin unions preferred in Arab Muslim communities as opposed to motherâ€™s brotherâ€™s daughter in the Dravidian Hindu states of South India and among the Han Chinese, does however indicate additional customary influences.
1.3 The Genetic Effects of Inbreeding
In consanguineous unions the partners share genes inherited from one or more common ancestor and, for example, in first-cousin marriages the spouses are predicted to have 12.5 percent of their genes in common. This means that on average their progeny will be homozygous at 6.25 percent of gene loci, i.e., they will have received identical gene copies from each parent at these sites in their genome. If the same mutant gene is inherited from both parents the individual will express the disorder, either at birth or later in life depending on the nature and site of the mutation, thus contributing to the phenomenon of inbreeding depression.
The coefficient of inbreeding (F) is a numerical estimate of the degree of inbreeding of an individual, and so for first-cousin offspring F = 0.0625. Similarly, for the progeny of uncle-niece unions F = 0.125, while for second-cousin offspring F = 0.0156. In many communities there is a long and continuous history of consanguineous unions, and so the cumulative level of inbreeding may be significantly higher than the value calculated for a single generation. Under these circumstances, a correction can be applied to account for the effects of ancestral inbreeding using the formula:
F= 2(1/2)n (1+FA )
where FA is the ancestorâ€™s inbreeding coefficient, n is the number of individuals in the path connecting the parents of the individual, and the summation (L) is taken over each path in the pedigree that goes through a common ancestor.
With a few notable exceptions, incest avoidance is, and appears to have been, a practice common to virtually all societies. Various explanations have been offered for incest avoidance including Freudian guilt, and theories ascribed to Levi-Strauss and others that it serves both to maintain the existence of the family and to encourage the establishment of affinal relations with other kin groups. According to the Westermarck hypothesis, incest avoidance arises principally because of negative imprinting against close associates of early childhood (van den Berghe 1983). Studies conducted on individuals raised under mixed-sex child-rearing regimes in Israeli kibbutzim have been cited in support of the negative imprinting theory, since they rarely marry or enter into sexual relationships (Talmon 1965, Spiro 1965). Perhaps more convincingly, a detailed investigation into the practice of sim-pua marriage in Taiwan, whereby a girl is adopted with the expectation that she will marry a son of the adoptive family, demonstrated aversion on the part of some intended spouses. Where a marriage did occur, sim-pua unions often were characterized by lower mean fertility and lesser marital stability (Wolf and Huang 1980).
2.1 Historical Examples of Dynastic and Non-dynastic Incest
There have been a number of societies in which dynastic incest was practised over multiple generations, including the Eighteenth and Nineteenth Dynasties and the Ptolemaic and Roman periods in Egypt, Zoroastrian Iran, the Incas, and the royal families of Hawaii (Middleton 1962, Shaw 1992). In Pharaonic Egypt, brotherâ€“sister or half-sister unions were regarded as a potent means of maintaining and strengthening the royal house and bloodline, although the Pharaoh also had ready access to other females who were non-relatives. Information has emerged on incestuous marriages outside these ruling classes. During the period of Roman Egypt, from the first to the third centuries AD: the records indicate that full brotherâ€“sister unions accounted for 19.6 percent of marriages in the city of Arsinoe, with a further 3.9 percent between half-siblings (Scheidel 1997). However, it has been argued that these unions may have been atypical, having been contracted in response to the restricted numbers of potential marriage partners in the minority Greek settler community. Among the Zoroastrians in Persia, the underlying rationale for incestuous unions appears to have been based on specific religious beliefs, and to have emerged just prior to the Arab invasion in 636 AD. All three types of incestuous union, fatherâ€“daughter, brotherâ€“sister, and motherâ€“son were advocated. In each case they were described as being of especial religious merit, with their practice a means of expiating mortal sin.
2.2 Incest in Contemporary Societies
There is the conundrum that, despite the claimed near-universality of an incest taboo, an extensive and growing literature exists on the occurrence of incest in contemporary Western societies. Most commonly these reports have emanated from case studies conducted either on persons examined because of intellectual handicap or in psychiatric clinics, thus leading to the general conclusion that incestuous relationships are highly detrimental to those classified as victims. In some cases, however, it has been suggested that the outcome need not necessarily be psychologically destructive, with women in stable marriages acknowledging earlier father-daughter sexual relationships which had commenced prior to puberty in the female. As will be discussed in Sect. 3.2, given the fact that incest is both illegal and widely regarded as morally reprehensible, it would be difficult to determine how common this latter response might be without exposing respondents to the risk of self-incrimination.
3. Biological Outcomes of Consanguinity and Incest
The first major study into the biological effects of inbreeding was conducted by Dr Samuel Bemiss of Louisville, Kentucky in 1858, using reports forwarded by medical colleagues on the outcomes of unions ranging from incest to third-cousin marriages. Since that time hundreds of additional studies have been undertaken based on a variety of sampling techniques, including pedigree analysis, household surveys, questionnaires administered to hospital in- and outpatients, Roman Catholic dispensation records, and surname analysis. In populations such as Dravidian South India, where uncle-niece (F= 0.125) and first-cousin unions (F = 0.0625) are preferential and jointly account for some 30 percent of marriages, unions beyond second cousins are of limited biological significance (Bittles et al. 1991). Conversely, in a country such as Finland where consanguineous unions are rare, or in endogamous communities in which close-cousin marriage has been proscribed on religious grounds, biologically remote relationships including third-cousin unions (F = 0.0039) may result in moderate levels of cumulative inbreeding through time and so prove to be of clinical relevance.
3.1 Measuring the Biological Outcomes of Inbred Marriages
In an attempt to rationalize the results of inbreeding surveys into a biologically meaningful and reproducible format, a method was devised to calculate the numbers of lethal gene equivalents in a community or population, by comparing death rates in the progeny of consanguineous and unrelated couples. Lethal gene equivalents are the numbers of detrimental recessive genes carried by an individual in the heterozygous state, which, if homozygous, would result in death and so add to the genetic load of the population. The number of lethal gene equivalents in a population can be calculated according to the formula:
loge S = A + BF
where S is the proportion of survivors in the study population, A measures deaths that occur under random mating, B represents deaths caused by the expression of recessive genes via inbreeding, and F is the coefficient of inbreeding (Morton et al. 1956). By plotting a weighted regression of the log proportion of survivors (S) at different levels of inbreeding (F), A can be determined from the intercept on the Y-axis at zero inbreeding (F= 0), and B (the number of lethal gene equivalents) is given by the slope of the regression.
Despite a number of limitations, this regression technique offers a simple and convenient method of assessing and comparing data on the effects of inbreeding in different populations. Through time, estimates of the mean number of lethal gene equivalents in the genome have been revised downwards, in part resulting from improved sampling techniques and the recognition that earlier surveys may have produced spuriously high values because of inadequate control for non-genetic variables. Most recently, an excess mortality rate of 4.4 percent was calculated for deaths among first-cousin offspring from approximately 6 months gestation to 10 years of age, equivalent to 1.4 lethal genes per person (Bittles and Neel 1994). The measurement of postnatal morbidity is less precise since it is reliant on the diagnostic criteria employed. As a result the estimates obtained can vary quite widely, e.g., from 1.4 percent to 4.1 percent for total morbidity prior to the age of reproduction (Schull and Neel 1965).
3.2 The Biological Outcomes of Incest
As first degree relatives have 50 percent of their genes in common, the progeny of an incestuous union will be homozygous at 25 percent of loci and so F = 0.25.
Given the strongly antagonistic legal and social attitudes to incest, direct assessment of associated biological outcomes may be subject to significant ascertainment bias, since a detailed examination including determination of paternity may only be initiated if a child shows symptoms of physical and/or intellectual handicap. The net result is a paucity of data, which may or may not reflect the incidence of incestuous pregnancies that successfully proceed to term. Problems can also arise in attempting to control for the potentially adverse effects of non-genetic variables, which include maternal and paternal age, parental disease, and unsuccessful attempted interruption of the pregnancy.
3.3 Direct Examination of the Progeny of Incest
Table 1 comprises data from the four most comprehensive published studies of incest. The first and obvious observation is that very few cases have been systematically investigated, surprisingly so since the topic of incest features prominently in the social and behavioral literature. Three of the studies were prospective, and in one investigation strenuous efforts were made to recruit matched non-incestuous controls (Adams and Neel 1967). There were no control subjects in two of the other studies (Carter 1967, Baird and McGillivray 1982), and the brief report by Carter (1967) was further restricted by a lack of information on the physical and mental status of the parents or their socioeconomic background. In several studies the period of follow-up was brief, and so disorders with a later age of onset may not have been detected. By far the largest survey was that of Seemanova (1971),conductedretrospectivelyintheformerCzecho-slovakia on incestuous births reported between 1933 and 1970. An ingenious approach to the problem of controls was employed, with the outcomes of incestuous matings compared to those of pregnancies undertaken by a subset of the same women with unrelated partners. Unfortunately, the methodology could not overcome the fact that the physical and mental status of these women, 33 percent of the original total, was significantly superior to the remainder of the study group. In addition, many of the incestuous pregnancies had taken place when the women had just completed menarche, with mean and modal ages of 18.9 and 16 years in the fatherâ€“daughter matings and 19.9 and 14 years in the brotherâ€“sister matings, versus 24.9 and 21 years in the married pregnancy group. As very young maternal age is associated with an adverse pregnancy outcome, these discrepancies while unavoidable nevertheless cause significant problems in comparing the test group and their half-sibs.
How then should these four sets of data be assessed? Clearly, the mean rate of physical and mental ab-normalityof 39.4 percent isvery high. But, asdiscussed in Sects. 2.2 and 3.2, the collection of data on this subject is extremely difficult and, as acknowledged by several authors, control for non-genetic variables in the incestuous unions may have been incomplete. In the two studies for which unrelated reference groups were available, 9 of the 113 control children died or had a serious defect (8.0 percent). Thus the mean excess level of death and severe defect in the offspring of incestuous unions was 31.4 percent, not all of which was necessarily genetic in origin.
3.4 Comparison of Incest with Other Categories of Inbred Union
The second major method of estimating the probable levels of defect in the progeny of incestuous matings is based on information gained from legal consanguineous unions. For example, it is assumed that as the progeny of an incestuous mating have a coefficient of inbreeding of F = 0.25, their levels of disease and disability will be four times higher than in first-cousin offspring (F= 0.0625). The main advantage of this approach is that information on first-cousin unions is more plentiful, and it is less likely to be subject to bias during data collection. A potential disadvantage is that the relationship between the level of inbreeding and rates of disease and disability may be nonlinear, with disproportionately larger increases in the prevalence of deaths and defects at closer degrees of inbreeding. This situation could arise if incest was associated with increased rates of conditional lethals, genes that are only expressed under especially stressful circumstances, as might be encountered in an incestuous pregnancy. To date there has been no evidence that conditional lethals are expressed in the progeny of close kin unions. Therefore the excess mortality rate of 4.4 percent derived for deaths among first-cousin offspring (Bittles and Neel 1994) can be applied to estimate the prevalence of lethal defects in an incestuous pregnancy, i.e., 16 percent to 20 percent excess deaths. Likewise, from Schull and Neel (1965) excess morbidity among incestuous offspring would predictably range from 6 percent to 16 percent, suggesting a total rate for excess death and major disability in children born to first-degree relatives of between 22 percent and 36 percent.
The data currently available on the outcomes of both legal consanguineous marriages and incestuous relationships merit further examination and updating. Since the major study undertaken by Schull and Neel (1965) in Japan no comparably detailed investigation has been attempted, despite the remarkable epide-miological transition which has occurred during the last two generations. Across Asia, genetic disorders are becoming increasingly obvious as deaths due to infectious diseases decline, and early childhood mortality is replaced by extended morbidity. This change is especially important among couples in consanguineous unions, where higher rates of genetic disorders are to be expected, involving both autosomal reces-sives and polygenic disorders. In fact, because of better access to diagnostic and health care facilities, the burden of genetic disease will probably be most obvious and of greatest immediate significance among migrants from Africa and Asia now resident in North America, Western Europe, and Australasia, who have chosen to continue their tradition of close kin marriage. With respect to incest, it seems remarkable that the voluminous social and behavioral literature is still so inadequately matched in biological terms. Studies to identify the precise nature, extent, and timing of any genetic defects that may be expressed are needed, especially since in a significant proportion of cases the children of incestuous unions are offered for adoption. The advent of DNA-based analytical methods will greatly facilitate this process, and provide information of previously unparalleled insight and sophistication. In the interim, appropriate caution should be exercised in judging the biological outcomes of all categories of close kin union.