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Consanguinity, Inbreeding, and Genetic Drift in Italy (MPB-39)
By Luigi Luca Cavalli-Sforza Antonio Moroni Gianna Zei Princeton University Press
Copyright © 2004 Princeton University Press
All right reserved. ISBN: 978-0-691-08992-8
Chapter One
History of This Investigation and Structure of This Book
1.1 INTRODUCTION
The study of inbreeding, the consequence of the mating of relatives, has an important place in genetics. The similarity of the paternal and maternal contributions caused by the mating of relatives leads to increased genetic homogeneity of inbred individuals. A table of the expected effects of inbreeding in successive generations of selfing (crossing with self), the closest mating possible, which often occurs spontaneously in many plants, appears in Mendel's article, the founding paper of genetics. Thus, Mendel was also the first population geneticist.
Human societies are unique in keeping records of their own ancestry, sometimes, though very rarely, for thousand of years or more. Some breeders of domestic animals, however, have kept records of their animals' ancestry for even longer periods, measured in terms of numbers of generations.
The genetic effect of inbreeding can be estimated by the increase in average homozygosity over that expected by random mating. Homozygosity is the average percentfrequency of homozygotes-individuals receiving the same form of a gene from both parents. The complement to 100% of homozygosity is heterozygosity.
Matings of close relatives (often called consanguineous matings), if repeated for many generations, increase homozygosity to a point of seriously decreasing fertility and individual survival, making prolonged inbreeding incompatible with continuation of life. To obtain stocks of high genetic homogeneity, animal breeders often make recourse to systematic parent-child or brother-sister matings for a number of generations (twenty or more). In the process they lose many inbred lines because of loss of fertility or survival, and at best end with stocks of weak or delicate constitution (inbreeding depression). There are examples of repeated brother-sister marriages in ancient Egyptian and Persian dynasties; but, for reasons probably not of genetic nature, no dynasty lasted for periods long enough to expect serious inbreeding depression. In any case we have no records from which to observe it. But apart from these examples of encouragement of brother-sister marriages, which was still popular in the Egypt of Cleopatra's time, unions between brother and sister and parent and child are condemned and avoided in practically all human societies. The term "incest" refers to these tabooed unions. They occur, though rarely. Children of incest are very rare, of the order of 1/10,000 in an estimate in Michigan (Adams and Neel 1967).
The dangers of close inbreeding must have become known to early humans fairly soon, since practically every society has rules that tend to avoid close consanguineous marriage, and sometimes extend prohibition to remote consanguinities. This is especially true of very small communities, like those of Eskimos living in extreme northern latitudes (Sutter and Tabah 1956), which are under greater risk of reaching high levels of inbreeding. In one remote, very small, and highly isolated Greenland Eskimo community, no marriage closer than third cousins was found in genealogies from living individuals.
Animals also tend to avoid close inbreeding, by social customs that seem to have been favored by natural selection in response to inbreeding depression. In most Primates, social groups are fairly permanent, but young males reaching puberty tend to leave the group into which they were born and join other groups. This custom is clearly effective in limiting close consanguineous matings. Chimpanzees are the only exception, as here it is the females that leave the group. Among humans one likewise observes a greater tendency of females to leave their birthplace at marriage. Wives tend to move to their husbands' residence in 70% of traditional societies (Murdock 1967). This custom has important genetic consequences: mitochondrial DNA (mtDNA), which is transmitted by the maternal line, should show less geographic clustering than Y chromosomes, which are transmitted by the male line. This expectation was confirmed by observation (Seielstad et al. 1998). In fact, the Y chromosome shows greater genetic variation between populations than nonsexual chromosomes and mitochondrial DNA.
In addition, at least in chimpanzees and other mammals, some tendency to avoid brother-sister or parent-child mating is observed. Among humans, the social custom of avoiding marriage of close relatives is paralleled by a similar constitutional safeguard against brother-sister mating, in the form of the so-called Westergaard effect: a tendency to avoid sexual contacts between brother and sister, or, in general, children who have been brought up together. Puberty seems to be the dividing line between social contacts that are unfavorable (before puberty) or favorable (after it) to interest in establishing sexual relations between individuals of opposite sex. Research has shown that children brought up in the same kibbutz, where they were usually raised together, marry very rarely, if ever. An old Chinese custom, which survived in Taiwan until recently, is the adoption of a young girl by a family in which a son was born, so that this girl becomes his future wife. These so-called "minor" marriages have been shown to be, on average, less fertile and less long-lasting than ordinary marriages with girls not brought up in the family (Wolf 1980).
There are, however, social exceptions to the rule of avoidance of close consanguineous marriages, less close than brother-sister. In certain social groups such marriages may be much more popular than would be expected by chance, undoubtedly because of a social preference. In West and South Asia two types of consanguineous marriages are especially common: uncle-niece marriages comprise up to 20% of all marriages in several north Indian tribes, and first-cousin marriages reach 50% or more in many Middle Eastern ethnic groups (Arabs, North Africans, and some Jewish groups). First-cousin marriages are or were high in Japan, especially at a time when marriages were mostly arranged by parents. High consanguinity customs spread around with the people who developed them. Perhaps as a remote consequence of Arab domination in Sicily and southern Italy in the eighth to the eleventh centuries, the frequency of uncle-niece and first-cousin matings became high in these regions and is currently especially high in Sicily. These relatively moderate degrees of inbreeding do not seem to have had a truly damaging effect. They may have contributed to lowering the current frequency of lethal and semilethal genetic diseases, at least in Japanese populations (Cavalli-Sforza and Bodmer 1971, 1999).
By definition, recessive genes are those that are manifested only in homozygotes. In inbred families increased homozygosity is expected, leading to a higher probability of observing recessive inheritance. The study of consanguineous marriages, therefore, has merit for the detection of recessive genes and for the study of their frequency.
In this chapter we summarize the salient points of the history of this investigation, which started in 1951 and is now coming to an end. We then briefly summarize the main properties of consanguinity, inbreeding, and drift, as well as inbreeding effects in humans and some special projects that were part of the investigation. Finally, we summarize the structure of this book.
1.2 HISTORY OF THIS RESEARCH
In 1951 Luca Cavalli-Sforza started teaching a course in genetics at the Faculty of Sciences of the University of Parma, Italy. Among his students was Antonio Moroni, a priest who is now professor of ecology at the University of Parma. At that time Moroni taught natural sciences at the Seminary of the Parma Archbishopric and made Cavalli-Sforza aware of records in the Roman Catholic archives that could be of interest for human genetics: essentially dispensations for consanguineous marriages and parish books of deaths, marriages, and baptisms. In an almost 100% Catholic country, baptisms are a close equivalent of birth records. Newborns are usually baptized very soon after birth, and a very small fraction, probably less than 1%, dies without a chance to be baptized. Moroni was also instrumental in obtaining permission from the higher religious authorities to use these records for genetic investigations. Our investigations began at the bishopric of Parma. They were soon extended to other bishoprics, and eventually to the whole country of Italy. To help with our investigations, a letter from the highest Catholic authorities was sent by the Vatican to all parish priests, asking them to make parish records available for scientific purposes. Genetic research using Roman Catholic records was also started in France by Jean Sutter and his collaborators, at about the same time as ours.
Consanguinity records are to be found in various Catholic archives. Consanguinity itself is very carefully defined and Roman Catholic legislation prescribes with great precision which marriages are completely forbidden, which ones are permitted under dispensation from a higher religious authority, and which do not require dispensation. Priests receive formal teaching about these rules in seminaries in which they also learn to evaluate accurately the degree of consanguinity of candidates for marriage. The need for dispensation has changed through time and is now reduced to a minimum. In earlier times even remote degrees of consanguinity were forbidden and it was essential to ask for dispensations before marriage could be celebrated. A consanguineous marriage celebrated without the requested dispensation would be null and void, generating a very serious social problem for the families.
Chapter 2, on the history of consanguinity regulations in the Roman Catholic Church, examines the historical knowledge available. There are also geographic differences in rules for obtaining dispensation. In peninsular Italy the parish priest must check every pair of prospective spouses for the existence of recent relationship, and if one requiring dispensation is discovered, he must request it from the bishopric. A copy of the request is then sent from the bishopric to the Vatican, and is returned to the bishopric with the Vatican response and then to the parish before a marriage requiring dispensation can be celebrated. In a few regions other than peninsular Italy, dispensations for at least some less close consanguinities could be given by a local Catholic authority other than the Vatican.
At least in peninsular Italy, therefore, there are three sources of records: the priest is supposed to indicate on the parish marriage book that a specific marriage required a dispensation, but we found that in some parishes this was not always carefully done. Folders keeping full records of dispensations are kept in each bishopric, and a slightly less complete set of records is available in the Vatican archives. It is rare that a dispensation is not approved by the Vatican, if it is dispensable. Genealogical trees of the candidate spouses reconstructed by the parish priest are extremely common in the bishopric archives that we investigated, and are available for practically every dispensation requested, but much less frequently in the Vatican archives. These genealogical trees are essential for checking the consanguinity degree calculated by the priest and for testing hypotheses on age and migration effects, to be described in a later chapter. The presence of genealogies in the dispensation folders made it possible to check for errors in the calculation of consanguinity degrees. Errors were nonexistent or exceptional, not surprisingly, since the method of computation is regularly taught to priests at seminaries.
Our work was based initially on bishopric records. After a full study of dispensations deposited in the archives of the Archbishopric of Parma-the diocese of the city where the university in which Cavalli-Sforza taught from 1951 to 1962 is located-those of the two adjacent dioceses of Piacenza and Reggio Emilia were also investigated. The territory of these three dioceses and cities has almost identical ecological structure, extending from the Appennine mountains to the lowest part of the plain of the Po River. The three dioceses form the northern moiety of the administrative Italian region called Emilia, practically at the center of the Po valley, in the northern part of Italy. The Po River flows just north of the city of Piacenza, and continues eastward toward the Adriatic Sea. Parma and Reggio Emilia are on a major Roman road, the Via Aemilia, an almost straight line in the Po valley leading east-southeast from Milan to Bologna. The region around the Po and the Via Aemilia is a very fertile plain. Proceeding from each of the three cities toward the south, one enters first a hilly region and then a mountainous one. Population density is maximum near the cities, which are all located not far from the center of a very prosperous agricultural region. The mountainous region at the southern end of each diocese has the lowest population density. It is a part of the Appennine chain, the crest of which separates Emilia from Tuscany. The hilly region, intermediate between the plain and the mountains, has intermediate population density. The size of villages is on average highest near the cities and decreases regularly toward the mountains. This variety of environments of each diocese has helped in the investigation of the effects of the relevant ecological and demographic variables.
Bishopric records of the islands of Sardinia and Sicily, as well as of some other islands and inland regions of special interest, were also investigated, showing similar effects of demographic variables, along with other characteristics of each region. Records of individual dioceses of the islands were published earlier; their analysis has been repeated by partially new approaches for the purpose of preparing this book.
In later years it was possible to establish a team of young students who copied the consanguinity records of the Vatican archives under direction of Father M. Bracco. These records included all of peninsular Italy from 1911 to 1964, except for Sicily, which had independent rules. It was necessary to visit directly the bishoprics of Sardinia and Sicily, but our survey of Sicilian dioceses was not complete.
Full names of consanguineous couples were available. They were kept confidential, but we had permission to use them for linking them with other records to study the effect of consanguinity on certain phenotypes. The records were eventually transferred to computer tapes, analyzed statistically, and ordered alphabetically.
Results on some of the bishoprics were in part published earlier. But the major analysis, that of the Vatican records, is published for the first time in this volume. A number of other new calculations were carried out on the available records and are included in this book. Other socioeconomic investigations done in Italy were studied and correlated with the consanguinity data. Socioeconomic information came from the Istituto Centrale di Statistica.
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