A global overview on consanguinity

A.H. Bittles

Table of Contents

A global overview on consanguinity

References

A global overview on consanguinity

In human societies marriages usually occur within quite narrow geographical boundaries, which effectively limits the degree to which genes are transmitted. Genetic admixture is further restricted by positive assortative mating, i.e., by individuals choosing a marriage partner not only from the same geographical area but also with similar physical characteristics, religious beliefs, educational backgrounds, and even political opinions. Marriages within specific clans or tribes largely remains the rule in more traditional societies, and marital endogamy also is strongly favoured in many migrant communities resident in western countries. A number of factors govern the influence of endogamy on community gene pools, such as the number of founders and the age of the community; the size of the community and the rigidity of its marriage boundaries; and population amalgamations, including adoption and religious conversions. Frequently these variables are community-specific in their action and hence in their impact on gene pool composition.

Table1.Consanguineous Relationships

Relationship / Genes in common (%) / Homozygosity in progeny (%) / Coeeficient of inbreeding (F)
Double first cousin / uncle-niece / 25 / 12.5 / 0.125
First cousin / 12.5 / 6.25 / 0.0625
Second cousin / 6.25 / 1.56 / 0.0156

Consanguineous marriage is generally uncommon in Europe, North America and Australasia. By comparison, consanguinity is strongly favoured and is believed to offer significant social advantages in many parts of North and sub-Saharan Africa, the Middle East, and West, Central and South Asia, where some 20% to over 50% of all unions are between couples related as second cousins or closer. Besides major religious differences, local and regional social regulations and beliefs can influence the prevalence and specific types of consanguineous marriage contracted. Community endogamy and a widespread preference for consanguineous unions both result in a higher level of homozygosity, which in turn would be expected to result in a greater prevalence of recessive disorders. However, there may be major differences in the profiles of deleterious mutations within and between communities; for example, specific disorders often are unique to individual clans or tribes in the Gulf region.

Figure1.Global Distribution of Consanguineous Marriage

A large multi-national study showed that prereproductive mortality was 4.4% higher in first cousin progeny (F = 0.0625) than in the offspring of non-consanguineous unions. A number of qualifications need to be made in the interpretation of these results. Most of the studies cited were conducted in low income countries with high background levels of early mortality, and consanguinity-associated deaths were largely concentrated during the first year of life. Due to poor diagnostic facilities a specific cause of death was seldom identified, and so the precise contribution of genetic disorders to premature mortality was unclear. There also was limited control for the effects of non-genetic variables that are known to have an adverse influence on mortality in the early years of life, such as restricted birth interval, maternal illiteracy and young maternal age. The near-global transition from high infant and childhood mortality to extended morbidity has meant that many people with major inherited disorders now survive into adulthood, which has several important implications. At the family level it could create difficulties for parents who feel obliged to fulfil their parental obligations by arranging a marriage for affected offspring. From a wider perspective, the shift in disease profile may in time influence community opinion away from consanguineous marriage. In terms of future health care delivery, it highlights the requirement to investigate the influence of consanguinity (and endogamy) on adult-onset diseases.

Consanguinity and Recessive Gene Expression

Table2.Proportion of Affected Offspring

Gene frequency, q / Unrelated parents, q2 / 1st cousins, q2+(1/16)pq / Factor increase
0.1 / 0.01 / 0.0156 / 1.56
0.0.1 / 0.0001 / 0.000719 / 7.19
0.001 / 0.000001 / 0.000063 / 63.0

Table3.Estimated consanguinity-associated mortality

Country / Mean coefficient of inbreeding (α) / Estimated consanguinity-associated deaths
Bahrain / 0.0159 / 11.2/1,000
Egypt / 0.0230 / 16.2
Iran / 0.0131 / 9.2
Iraq / 0.0235 / 16.5
Jordan / 0.0246 / 17.3
Lebanon / 0.0091 / 6.4
Oman / 0.0198 / 13.9
Pakistan / 0.0331 / 23.3
Palestine / 0.0198 / 13.9
Saudi Arabia / 0.0208 / 14.6
UAE / 0.0245 / 17.2

Although the role of consanguinity in the prevalence of recessive disorders has been extensively investigated, it is endogamy which principally governs the spectrum of observed diseases in a community. For this reason, the presence of multiple discrete sub-populations creates substantial practical difficulties in the organization of disease registers and screening programmes for genetic disorders at national and even regional levels. Endogamy and preferential consanguineous marriage also have significant practical implications for disciplines such as pharmacogenetics, since the choice of appropriate study and control populations will pose major problems in a country with multiple discrete sub-communities, and a treatment that is successful in one community may be clinically ineffective in others.

References

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