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.
Table 1. Consanguineous Relationships
Relationship
Genes in
common
(%)
Homozygosity in
progeny (%)
Coeeficient of
inbreeding
(F)
Double first
cousin / uncleniece
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.
Figure 1. 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
Table 2. Proportion of Affected Offspring
Gene
frequency, q
0.1
Unrelated
parents, q2
0.01
1st cousins,
q2+(1/16)pq
0.0156
Factor
increase
1.56
Gene
frequency, q
Unrelated
parents, q2
1st cousins,
q2+(1/16)pq
Factor
increase
0.0.1
0.0001
0.000719
7.19
0.001
0.000001
0.000063
63.0
Table 3. Estimated consanguinity-associated mortality
Country
Mean coefficient of
inbreeding (α)
Estimated consanguinityassociated 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
1. Bittles AH, Neel JV. (1994) The costs of human inbreeding and their
implications for variations at the DNA level. Nature Genetics 8, 117-121.
2. Bittles AH. (2001) Consanguinity and its relevance to clinical genetics. Clinical
Genetics 60, 89-98.
3. Bittles AH. (2003) Consanguineous marriage and childhood health.
Developmental Medicine and Child Neurology 45, 571-576.
4. Hussain R. (1999) Community perceptions of reasons for preference for
consanguineous marriages in Pakistan. Journal of Biosocial Science 31, 449461.
5. Teebi AS, Farag TI. (eds.) (1997) Genetic Disorders among Arab Populations,
New York, Oxford University Press.
6. Zlotogora, J. (2002) Molecular basis of autosomal recessive diseases among
the Palestinian Arabs. American Journal of Medical Genetics 109, 176-182.