Coordinated by Roberta PACE, Alain PARANT

 

Matrimonial practices, population genetic structures and public health in the Mediterranean region

 

Gil BELLIS

Institut national d’études démographiques (INED), Paris

 

Abstract: This article deals with consanguineous unions from the standpoint of population genetics. The factors underlying this type of union will be examined first of all, followed by a presentation of the formal measurement of consanguinity in order to obtain an overview of the practices and levels of consanguinity observed in the Mediterranean region. The second part of the paper seeks to establish a link between consanguinity and its consequences on the genetic structure and the morbidity/mortality of populations where a certain number of genetic diseases, representative of a few countries in the Mediterranean Basin, are present. The third part will discuss the principal public health measures adopted by different countries in order to reduce the burden of these diseases. The paper’s conclusion will assess the effectiveness of the individual and collective strategies implemented to avoid the diseases in question.

Keywords: consanguinity, genetic diseases, public health policies, genetic counselling, prenatal diagnosis, screening.

 

 

1.          INTRODUCTION

Unions between men and women can take very different forms, depending on the country, the period in history, and the laws and customs in force. One peculiarity of matrimonial practices is consanguinity. Consanguineous marriages characterize a reproductive regime where unions take place between related individuals. In this regard, two aspects may be considered: on the one hand, the causes of consanguinity, which are linked not just to the – possibly very local – characteristics of the matrimonial circle in which individuals who are likely to marry move, but also to individual behaviours regarding marriage or the cultural attitudes that guide individuals’ choice of spouse; and, on the other hand, the consequences of consanguinity, which are concerned with the genetic effects of such unions on the health risks affecting a population, or on the perpetuation of a certain number of hereditary diseases. This article will therefore first take stock of the situation regarding matrimonial practices and the levels of consanguinity observed in the Mediterranean region, followed by their consequences on the genetic structure and morbidity of the populations concerned; it will then describe the public health measures adopted by different countries to try to reduce the burden of certain particularly frequent genetic diseases in the Mediterranean Basin.

2.         CONSANGUINITY IN THE MEDITERRANEAN REGION

In everyday use, the meaning of the word “inbreeding” is quite close to the definition of the more formal “consanguinity”, derived from Latin terms meaning “to share the same blood”. However, to avoid all ambiguity, we shall use the term “consanguinity” throughout, in the strictest sense of the word: i.e. the genetic relation between descendants of a common ancestor. At the origin of this biological link between individuals, two key factors can be identified. The first, structural in nature, is linked to human populations whose numbers have remained limited over many generations or which became established in geographical spaces conducive to isolation, such as islands or poorly accessible mountain valleys; moreover, limited numbers and isolation can take different forms and be observed, for example, within religious, or even occupational, isolates. In these situations, the restriction of the circle of marriageable individuals and the almost total absence of migratory exchanges provide favourable conditions for areas of intermarriage where the choice of spouse takes place not at random but within a relatively closed group of individuals that may belong to the same family line. The second factor, cultural in nature, is based on an expected benefit of marriage when a union occurs between two related persons. This benefit is social, first of all, in cases where the marriage is likely to encourage the integration of the female spouse into the family, ensure greater cohesion within the family environment, guarantee the stability of the union by reducing the possibility of divorce, and provide more possibilities for taking care of children who are sick or disabled within a sufficiently dense family network. But there is also an economic benefit, in cases where the husband assigns property to her wife for succession-related reasons – a practice that historically was common among the Germanic peoples and which today principally occurs in Islamic societies. In the traditionally patriarchal Arab world, unions with female patrilateral parallel cousins (daughters of one’s father’s brother) anticipate the inheritance rights from which a man’s agnatic relatives benefit. By virtue of this practice, and provided that the wife has had at least one child, the land and/or property – the dower – assigned by the husband to his wife are transferred to her if she is widowed or divorced; she then becomes the owner of this property and will later pass it on by inheritance to her children, ensuring it ultimately comes back to her husband’s family.

Whether a union between related individuals is due to structural or cultural factors, the genetic relationship between descendants of a common ancestor is measured by a coefficient of consanguinity, denoted by F, which expresses the probability that two alleles possessed by an individual I at a given locus are identical by descent (see Annex 1). For a child born of a union between first cousins, where F=0.0625, the coefficient of consanguinity indicates that, in concrete terms, for 1 gene out of every 16 in his or her genome – i.e. 6.25% – both alleles of this gene will be identical by descent, thus creating a situation of homozygosity (see Annex 2). In a population where matrimonial practices are heterogeneous, with the majority of unions being panmictic[1] and a fraction of the total number of unions being between related persons as a result of the existence of social or cultural rules, the mean coefficient of consanguinity is equal to the mean of the various individual coefficients weighted by the frequencies of the various types of crosses between related individuals. An overview of the frequency of consanguineous marriages throughout the world is shown on Map 1.

 

Map 1. Frequency of consanguineous marriage throughout the world

      Source: A. H. BITTLES, M. L. BLACK, Global Patterns and Tables of Consanguinity, 2013 [http://consang.net] – retrieved May 2014

Around 20% of the world’s population lives within communities where consanguineous marriages occur, with the highest frequencies generally observed in rural or economically disadvantaged areas. In studies of populations, in order to arrive at a sufficiently sound interpretation of the risks associated with consanguinity, geneticists consider parameters such as the frequency of consanguineous marriages and the proportion of unions that do not exceed the sixth degree of kinship, in the terminology of French civil law, as the genetic effects are marginal at more distant relationship levels and comparable to non-consanguineous unions. The terminological equivalencies for the different types of consanguineous union are given in Table 1 below. The documented data on the parameters of interest that enable the characterization of levels of consanguinity in the Mediterranean region are summarized in Table 2.

 

 

Table 1. Terminology for types of union and corresponding coefficients of consanguinity

Type of union

Terminology used in French civil law

International terminology

Coefficient of consanguinity (F)

Double cousins

3rd degree of kinship

D1C

0.1250

First cousins

4th degree of kinship

1C

0.0625

First cousins once removed

5th degree of kinship

1.5C

0.0313

Second cousins

6th degree of kinship

2C

0.0156

 

Table 2. Characteristics of consanguinity in the Mediterranean region

Country

Type of union

Frequency of consanguineous marriages (%)

Mean coefficient of consanguinity (F)

Reference

Algeria – Urban

1C, 2C

27.5

0.0136

[2]

Algeria – Rural

1C, 2C

34.0

0.0169

[3]

Croatia

1C

0.1

[4]

Egypt – Urban

D1C, 1C, 1.5C, 2C

22.1

0.0092

[5]

Egypt – Rural

D1C, 1C, 1.5C, 2C

39.1

0.0147

[6]

Spain

1C, 1.5C, 2C

4.1

0.0014

[7]

France

1C, 1.5C, 2C

0.8

0.0002

[8]

Israel – Muslims

D1C, 1C, 1.5C, 2C

32.1

0.0177

[9]

Israel – Christians

D1C, 1C, 1.5C, 2C

20.6

0.0119

[10]

Israel – Druze

D1C, 1C, 1.5C, 2C

40.9

0.0233

[11]

Italy

1C

0.5

0.0004

[12]

Lebanon – Muslims

1C

29.6

0.0109

[13]

Lebanon – Christians

1C

16.5

0.0049

[14]

Libya

1C, 2C

37.6

0.0209

[15]

Morocco

1C, 2C

19.9

0.0089

[16]

Slovenia

1C

0.6

[17]

Syria – Urban

D1C, 1C, 2C

27.5

0.0203

[18]

Syria – Rural

D1C, 1C, 2C

35.9

0.0265

[19]

Tunisia

1C, 1.5C, 2C

26.9

0.0213

[20]

Turkey

1C, 2C

20.1

0.0110

[21]

Source: A. H. BITTLES et al., cit.

 

 

According to Table 2, the highest levels of consanguinity have been observed in countries in the south (Algeria, Egypt, Libya, Tunisia) and east (Israel, Lebanon, Syria, Turkey to a lesser extent) of the Mediterranean region. Although linked to different types of union – for example, unions between double cousins do not seem to be commonplace whereas unions between first cousins can be found everywhere – the frequency of consanguineous marriages is greater than 20% in these countries, with the highest values observed in rural populations (Algeria, Egypt, Syria) or Muslim communities (Arab populations in Israel and Lebanon); as a corollary, the mean consanguinity level is also high and varies between 0.0136 (for urban populations in Algeria) to 0.0265 (for rural populations in Syria).

 

3.         GENETIC DISEASES IN THE MEDITERRANEAN REGION

Of the existing genetic diseases, the only ones that shall be considered here are monofactorial diseases, which are the classic hereditary diseases caused by deleterious mutations of genes and which are transmitted according to Mendel’s laws of inheritance[22]. If these deleterious mutations are found on autosomes, they will cause autosomal dominant or recessive diseases (see Annex 2) and will affect members of both sexes in the same proportions. The consequence of consanguinity on the genetic structure of populations is formalized in Table 3.

 

Table 3. Frequency of genotypes (two-allele genes) in panmictic or consanguineous populations

Genotype

Panmixia

F=0

Consanguinity

0≤F≤1

AA

p2

p2(1–F)+pF

Aa

2pq

2pq(1–F)

aa

q2

q2(1–F)+qF

 

According to the data in Table 3, a deleterious recessive allele with a frequency of, say, 5% in a population will lead to a frequency of homozygotes – and therefore of affected members – of 2.5‰ if the population is panmictic, but 5.5‰ if the mean coefficient of consanguinity in this population is 0.0625; this means that the relative increase in the risk of developing the disease due to consanguinity is a factor of 2.2 in this case. It is therefore clear that consanguinity – since it favours the union of similar alleles – modifies genotype frequencies by causing an increase in the number of homozygotes and a reduction in the number of heterozygotes; what is more, the relative increase in risk tends to rise with the reduction in frequency of the recessive allele, which has the effect of raising the genetic disorder in question above a certain visibility threshold, whereas it would have remained rare had unions not taken place between related individuals.

One very general indication of morbidity in Mediterranean populations can be found by examining the list of reasons for consultations in hospital paediatric departments: the proportion of genetic diseases varies by country, but represents between 8% and 20% of all consultations. Although it is difficult to conduct research in these areas because of a lack of suitable infrastructure or the absence of population registers, a certain number of epidemiological studies of genetic diseases representative of the Mediterranean Basin have nevertheless been carried out; following a literature review on this subject and the consultation of specialized databases[23], it has been possible to establish a non-exhaustive summary, presented in Table 4.

 

Table 4. A selection of genetic diseases present in the Mediterranean Basin

Disease (MIM#)

Heredity

Country or region

α-thalassaemia (604131)

Autosomal recessive

Algeria, Tunisia

β-thalassaemia (613985)

Autosomal recessive

Algeria, Cyprus, Egypt, Greece, Lebanon, Morocco, Sardinia, Sicily, Syria, Tunisia, Turkey

Bardet-Biedl syndrome (209900)

Autosomal recessive

Lebanon, Libya

Cystic fibrosis (219700)

Autosomal recessive

Algeria, Croatia, France, Greece, Italy, Lebanon, Libya, Morocco, Spain, Syria, Tunisia, Turkey

Familial Mediterranean fever (249100)

Autosomal recessive

Egypt, Greece, Israel, Italy, Lebanon, Libya, Morocco, Spain, Syria, Turkey

Glucose-6-phosphate dehydrogenase (305900)

X-linked recessive

Algeria, Egypt, Lebanon, Libya, Syria, Tunisia

Osteopetrosis with renal tubular acidosis (259730)

Autosomal recessive

Egypt, Tunisia

Sickle-cell anaemia (603903)

Autosomal recessive

Algeria

 

Unlike what is generally observed in other regions of the world, studies and databases on genetic diseases in the Mediterranean area show that there is a preponderance of autosomal recessive diseases: they represent around 63% of genetic diseases, compared with 27% for autosomal dominant diseases and 10% for other genetic disorders. The predominance of this type of heredity can be explained to a large extent by consanguinity. A number of complementary observations can be made on the basis of the data in Table 4. Prevalence of haemoglobinopathies (α- and β-thalassaemias, sickle-cell disease) and enzymopathies (glucose-6-phosphate dehydrogenase [G6PD] deficiency) is high (reaching levels of between 1 and 15 per 100,000) and the distribution of these disorders corresponds to areas of malaria exposure; indeed, for carriers – who are unaffected by the disorders and whose genotype is heterozygous – these diseases offer an adaptive advantage in malaria-prone areas. However, what is more surprising is that those affected by these diseases generally have very specific genotypes: in the case of β-thalassaemia in Algeria, for example, four or five mutations alone account for most diagnoses of deleterious anomalies in the gene; in around 65% of cases, thalassaemic subjects have a homozygous genotype, composed of the same two allelic variants, including when these variants are rare. This specific genotypic composition, which is found in Arab countries in particular, is the result of consanguinity. Indeed, certain of the diseases listed in Table 4 above are rarely found anywhere else in the world; this is the case, for instance, for Bardet-Biedl syndrome (estimated prevalence of 0.7 per 100,000) or osteopetrosis with renal tubular acidosis (fewer than 100 published cases). Here, in the case of these recessive diseases with rare allele frequencies, we have a typical situation where a high level of consanguinity, concentrated in a few families, has significantly increased the visibility threshold of the pathology. Two other diseases from Table 4 stand out from the rest: cystic fibrosis, a multi-organ disease found in many countries, the prevalence of which is around 12 for 100,000; and familial Mediterranean fever, an auto-inflammatory disease for which the highest prevalences (more than 50 per 100,000) are to be found in Israel and in Sephardic Jewish communities in Spain and North Africa.

4.         PUBLIC HEALTH STRATEGIES

The major public health problem posed by genetic diseases lies in the fact that these disorders are widespread, chronic and involve treatments – when indeed treatments exist – that are complex, restrictive, painful for those affected and costly for the public authorities. This public cost is first and foremost demographic in nature: it is estimated, for example, that the life expectancy at birth for new born babies with cystic fibrosis in France 40 years ago was approximately 10 years; today, this figure stands at around 50 years, or some 30 years less than the estimated life expectancy at birth for the whole population. But the cost is also economic: in France, the average annual cost of all services related to managing one patient with cystic fibrosis is €23,000; the total cost nationwide in 2004, for example, amounted to €115 million.

Advances made in the fields of genetics and medical technology today offer a serious alternative to conventional medical treatments, which are exclusively symptomatic in many cases. In the case of populations that are highly exposed to the appearance of genetic disorders, this alternative is based upon a principle of prevention and comprises two approaches.

4.1. Measures taken prior to the birth of affected individuals

Before those affected by genetic diseases are born, the genetic counselling of families at risk is the first measure to be implemented. This is a specialized medical consultation that takes the form of private interviews with one or both members of the expectant couple. Genetic counselling involves providing all the information necessary to enable the person(s) concerned to make decisions regarding reproductive choices. These include birth control, choice of partner, the possibility of adoption, genetic testing on the foetus, and artificial selection using a donor. Comprehensive information is provided on foetal screening: the sampling procedure, the risks posed to the foetus, and possible diagnostic errors or failures. An information package is typically provided, along with details of the natural history and predictors of the disease. Genetic counselling also extends to relatives of the individual or couple, who may also benefit from information on the risk of genetic disorders in the family.

After genetic counselling, the technique for detecting foetuses potentially affected by a given genetic disorder essentially involves prenatal diagnosis. This process – initially limited to taking foetal blood samples – today comprises chorionic villus sampling[24]followed by DNA amplification to seek out any mutations. This technique, which has been implemented since the late 1980s, has proved to be safe and reliable. Its advantages are its simplicity, its rapidity, its acceptance among parents, and its limited risks of infection and haemorrhage. The aim of prenatal diagnosis is to obtain a diagnosis within the first trimester of pregnancy; at the same time, however, the prospect of a termination can be traumatic for parents and, depending on cultures or religions, may raise ethical issues. To avoid this, fertile couples may, in more economically developed countries, opt for pre-implantation genetic diagnosis, despite the difficulties involved in becoming pregnant via this method, which has a success rate of between 20% and 30%. Pre-implantation genetic diagnosis involves screening for genetic anomalies on embryos obtained through in vitro fertilization. Following this screening, embryos that are not carriers of the anomaly in question are transferred to the uterus, while carrier embryos are destroyed. This procedure does not exclude the possibility of other detection tests being carried out during pregnancy and the option of termination being proposed in the event that these tests predict the incidence of a disability at birth.

4.2. Measures taken after the birth of affected individuals

What preventive solutions are possible when affected individuals have already been born? Here, a distinction must be made between two target populations: first, the individuals affected, for whom a national neonatal screening programme may be set up. It is widely agreed that neonatal screening is suitable only for frequently occurring serious diseases that can be detected via the identification of deleterious mutations, and for which treatments are available. This last criterion is essential as, when administered at the earliest opportunity, treatments and medical care can not only delay the appearance of symptoms that could worsen the patient’s state of health, but also reduce infant mortality and improve the patient’s quality of life. The second target group is the population at large, for whom the aim is to screen carriers – that is, heterozygotes – and those at risk of giving birth to a child affected by the disease, as well as individuals who, in view of their age, have a milder form of the disease.

These screening programmes involve numerous stakeholders and extensive resources. The success of such programmes lies in the participation of parents’ associations or voluntary organizations who can help to educate the population concerned. Furthermore, the relevant decision-making bodies must necessarily be informed of the nature of such programmes, so as to ensure their full cooperation. Another key category of stakeholders is doctors, and in particular paediatricians, obstetricians and geneticists; added to these are family-planning organizations, nurses and social workers. Finally, and depending on the populations concerned, the participation of religious leaders may prove a decisive factor. To ensure public awareness, screening programmes may be the subject of specific teaching in schools, popularization measures and dissemination via various media: television, radio, newspapers, poster campaigns and information leaflets. Screening programmes carried out among adults of reproductive age typically target all couples indifferently, that is to say both those that have previously had one or more children affected by the disorder in question – i.e. retrospective diagnosis – and those that have not yet had children – i.e. prospective diagnosis. In both cases, screening is accompanied by a procedure comprising genetic counselling and prenatal diagnosis.

4.3. Overview of the effectiveness of prevention measures

The disorder β-thalassaemia is a genetic disease for which the prevention strategy has been highly effective, although the most convincing results have been limited to a few Mediterranean countries, primarily Cyprus, Greece and Italy (southern mainland, Sicily, Sardinia). In Sardinia, for example, the assessment carried out in 1988 showed that the screening of carriers had concerned 11% of the total population; of the 664 homozygous foetuses conceived during the period 1977-1988, 91.5% had undergone a prenatal diagnosis followed by a termination. From 1977 to 2003, out of 6,566 prenatal diagnoses conducted, 1,649 resulted in the identification of an affected foetus and, of these, 1,628 (98.7%) were followed by a termination of pregnancy. The proportion of screenings that result in terminations increases regularly – it currently stands at 99.3% – and very much depends on how early in pregnancy the diagnosis is made. In the space of 15 years, the prevalence of β-thalassaemia has fallen by 90%, as a result of the very significant drop in the annual number of cases: in 2002, measurements showed that incidence at birth of this disease had fallen from 40 cases to 2.5 cases per 10,000 live births. The evaluation of the prevention programme highlighted a number of factors: an active information and education campaign; access to populations facilitated by the existence of villages of 2,000 to 3,000 inhabitants; the extension of screening to relatives of carriers and patients; full financing by the country’s health authorities; and the provision of appropriate facilities when these were requested. However, certain failures remain at local level, in some cases linked to the absence of information, diagnostic errors, false paternity declarations, and refusals to accept the prenatal diagnosis or a termination of pregnancy.

Cystic fibrosis is also a genetic disease that has benefited from preventive measures, albeit only in France within the Mediterranean region. In 2002, the French health ministry decided to introduce neonatal screening for cystic fibrosis throughout the country. This decision was based on a number of arguments: the results of epidemiological studies demonstrating the benefits of early detection on the nutritional characteristics of patients, the gains achieved following regional initiatives, and the availability and reliability of a genetic test. This neonatal screening programme has a number of characteristics worth highlighting. First, it transpires that the screening procedure provides precise information regarding the incidence of cystic fibrosis, which stands at 2.3 cases per 10,000 live births. Second, the way in which the disease is managed has been radically transformed: since 2002, a protocol has formalized the conditions for taking care of affected individuals in consolidated specialist centres, which have responsibility for an active list of at least 50 patients and which have health professionals on hand to perform all necessary examinations. Finally, the creation of a national cystic fibrosis register has revealed an increase in lifespan and an ageing of the population affected by the disease; the proportion of affected adults (patients aged 18 or over) has grown from 18.4% in 1994 to 35.4% in 2001 and 47.2% in 2010.

5.         CONCLUSIONS

The programmes implemented to combat genetic diseases are characterized by an extremely diverse range of approaches, owing to several factors. The first of these is national choices, which are critical: in Cyprus, the decision was made to introduce premarital screening for β-thalassaemia as a national policy, whereas Greece and Italy preferred to focus on screening before procreation. In any event, these choices must comply with three fundamental principles of medical genetics: the autonomy of the individual or couple, the right to accurate and comprehensive information, and the strictest respect for medical confidentiality. Another factor that explains the level of diversity observed is the availability of medical technologies, and more specifically the fact that prenatal diagnosis techniques are not yet easily transferable to less economically developed countries. Despite the burden that genetic diseases represent in these countries, the implementation of complex and highly technical procedures can be hampered by their high cost and the lack of appropriate facilities and qualified personnel in certain disadvantaged areas. A final factor that comes into play is the cultural environment, where popular beliefs can be vital in determining whether these programmes are accepted or rejected by the population.

 

Annexes

1. Coefficient of consanguinity

A gene can exist in different forms or variants: these are the alleles of this gene. Conventionally, the normal allele is denoted by A, while a refers to one of the mutated alleles of the gene. The coefficient of consanguinity F expresses the probability that two alleles of a gene – each present at a given point (the locus) on two homologous chromosomes – in an individual are identical by descent, that is to say that they are copies of the same allele originating in a common ancestor. The calculation of the coefficient of consanguinity based on genealogical data involves considering several events:

- Event E1: the allele a carried by the father (P) of the individual (I) was transmitted to I over n generations as far back as the ancestor (C); the probability of E1=(0.5)n.

- Event E2: the allele a carried by the mother (M) of I was transmitted to I over n' generations as far back as C; the probability of E2=(0.5)n'. The probability of both events E1 and E2 occurring (indicating identical origin) is equal to (0.5)n×(0.5)n'=(0.5)n+n'.

- Event E3: the ancestor C transmitted one of the two alleles present at the locus of the two homologous chromosomes – a or A, for instance – to each of his or her children; the probability of E3=0.5. Event E3 refers to the transmission of identical allele copies, bearing in mind the identical origin.

- In total, FI=(0.5)n+n'+0.5+0.5 or, in simpler terms, FI=(0.5)n+n'+1.

- The existence of several common ancestors for I leads to a sum that can be expressed by the following general formula: FI= Σ(0.5)n+n'+1.


 

 

 

 

 

 

 

 

 

 

In the case of a union between first cousins, both have 2 common ancestors situated 2 generations above them, which gives F=(0.5)2+2+1 + (0.5)2+2+1, which equals 0.0625 or 1/16.

 

2. Genotypes and phenotypes

For any gene present at a given point (the locus), each individual possesses two alleles. If both alleles are identical, i.e. AA or aa, the individual is a homozygote. If the two alleles are different, i.e. Aa, the individual is a heterozygote. This genetic constitution is called the genotype, and the physical expression of this genotype, such as a disease, is called the phenotype. If we consider that a deleterious gene situated on an autosome – i.e. a chromosome that is not a sex chromosome (X or Y) – the disease is said to be autosomal dominant when it occurs in heterozygotes: if A is the normal allele of the gene and a is the deleterious mutated allele, the genotype of those affected is Aa. The disease is said to be autosomal recessive when it occurs in homozygotes: the genotype of those affected is then aa. In the case of autosomal recessive diseases, heterozygotes (whose genotype is Aa) are unaffected by the disease and are sometimes referred to as carriers.


 

 

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[1] Panmixia refers to a sexual reproduction system where mating (and fertilization) happens at random.

[2] A. BENALLEGUE, F. KEDJI, “Consanguinité et santé publique : étude algérienne”, Archives françaises de pédiatrie, 41, 1984, pp. 435–440.

[3] Ibidem.

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[6] Ibidem.

[7] J. PINTO-CISTERNAS, G. ZEI, A. MORONI, “Consanguinity in Spain 1911–1943: general methodology, behavior of demographic variables and regional differences”, Social Biology, 26, 1979, pp. 55–71.

[8] J. SUTTER, M. GOUX, “L’évolution de la consanguinité en France de 1926 à 1958 avec des données récentes détaillées”, Population, 17, 1964, pp. 683–702.

[9] R. VARDI-SALTERNIK, Y. FRIEDLANDER, T. COHEN, “Consanguinity in a population sample of Israeli Muslim Arabs, Christian Arabs and Druze”, Annals of Human Biology, 29, 2002, pp. 422–431.

[10] Ibidem.

[11] Ibidem.

[12] M. FRACCARO, “A note on consanguineous marriages in Italy”, Eugenics Quarterly, 4, 1957, pp. 36–39.

[13] M. KHLAT, “Consanguineous marriage and reproduction in Beirut, Lebanon” American Journal of Human Genetics, 43, 1988, pp. 188–196.

[14] Ibidem.

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[16] N. LAMDOUAR BOUAZZAOUI, “Consanguinité et santé publique au Maroc”, Bulletin de l’Académie nationale de médecine, 178, 1994, pp. 1013–1027.

[17] A. C. STEVENSON et al., cit.

[18] H. OTHMAN, M. SAADAT, “Prevalence of consanguineous marriages in Syria”, Journal of Biosocial Science, 41, 2009, pp. 685–692.

[19] Ibidem.

[20] S. E. RIOU, C. YOUNSI, H. CHAABOUNI, “Consanguinité dans la population du Nord de la Tunisie”, La Tunisie médicale, 67, 1989, pp. 167–172.

[21] I. KOÇ, “Prevalence and socio-demographic correlates of consanguineous marriages in Turkey”, Journal of Biosocial Science, 40, 2008, pp. 137–148.

[22] The other types of genetic diseases are mitochondrial diseases, diseases caused by chromosomal aberrations, and multifactorial diseases.

[23] Centre for Arab Genomic Studies [http://www.cags.org.ae].

[24] This procedure involves gathering (by means of centesis, i.e. puncture and aspiration) a small piece of the tissue (the trophoblast) that surrounds the amniotic sac and the foetus.