Post on 11-May-2015
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Consanguinity
Advanced Topics Advanced Topics in Genomicsin Genomics
6-10-20116-10-2011
Prof. Moein Prof. Moein KanaanKanaan
Amer WazwazAmer Wazwaz
Consanguinity is a term, derived from two Latin words "con " means common, or of the same and "sanguineus " means blood Hence, referring to a relationship between two people who share a common ancestor or blood
In genetics, a consanguineous marriage means union between couples who are related as second cousins or closer Alwan A, Modell B
Endogamy is the marriage within a specific group or class with in the same population [isolated populations, small towns, villages or tribes]
IntroductionIntroductionLittle quantitative information on consanguinity is available from regions of high predisposition to consanguineous marriages
Different religious and cultural opinions and subsequently legislatives, most of them prohibit or even ban consanguineous marriages; especially first-cousin marriages
10.4% of the global population are related as second cousins or closer
Mortality in first-cousin progeny is ~3.5% higher than that in non-consanguineous offspring
Although the overall prevalence of consanguineous marriage seems to be declining, in some countries the present rates of consanguinity exceed those of the preceding generations like Qatar, Yemen, and UAE Tadmouri G.O et al
The Current Global Prevalence of Consanguineous Marriage
Global distribution of marriages between couples related as second cousins or closer
Consanguinity rates vary from one population to another depending on religion, culture and geography
Consanguinity Rates in Arab Populations
>1C Double first-
cousin marriage
1C First-cousin marriage
Source: Tadmouri G.O et al, Reproductive Health 2009.
Consanguinity Extent and Complexity
Influences and outcomes of consanguineous marriages
Contrasting biological and social outcomes of consanguineous marriage in
traditional rural and modern urban settings
Consanguineous marriages are generally thought to be more stable than marriages
between non-relatives
Societies with high consanguinity rates have to
understand and prevent the deleterious impact of consanguinity on health.
Guidelines for health care providers to assist them in
counseling for consanguinity
Population Stratification
Population stratification has critical importance in studying consanguinity-associated morbidity and mortality
Greater importance in larger populations with more diverse genetic origins
Population substructure often results in variant marker allele frequencies in different subpopulations
In most populations the clan or its hereditary equivalent may be the most logical unit for genetic screening
Influence of Consanguinity on Complex Diseases
Consanguinity expected to exert a greater influence on the complex diseases if rare autosomal recessive alleles were causally implicated, Whether in common disease/common variant or common disease /rare variant
While if the involved disease alleles are common in the gene pool, then intra-familial marriage would have a relatively lesser effect
Different impacts on adulthood complex diseases & congenital defects
For example: +ve for Schizophrenia and Alzheimer -ve for Breast Cancer and Hypertension
Dalmatian islands study indicated a positive association between inbreeding and a wide range of adulthood disorders
Ubiquitous involvement of rare autosomal recessive genes in adult-onset complex diseases. As an increasing in the genomewide heterozygosity after a decline in consanguineous marriage, lead to a widespread reduction in the burden of complex diseases
Pakistani community in the United Kingdom study examined the influence of first-cousin marriage on autosomal recessive single-gene disorders
A 7/1,000 increase in autosomal recessive disorders per 0.01 increase in the mean coefficient of inbreeding .
In the Pakistan national population, where 50% of marriages were between first cousins. Some 22/1,000 extra single-gene disorders would be expected
Comparative mortality in first cousin versus non-consanguineous progeny in 69
study populations
1C first cousin NC non-consanguineous
mean excess mortality at first-cousin level of 3.5%
Consanguinity and Consanguinity and Susceptibility to Infectious Susceptibility to Infectious
Diseases in HumansDiseases in Humans At least in Animal
Populations
Low genetic heterozygosity is a risk factor for infection by a diverse range of pathogens
In This Study
Microsatellite genome screen data
for tuberculosis, hepatitis and leprosy, used to test the
hypothesis that inbreeding depression increases risk of
infection
Studies link between genetic diversity and disease susceptibility are increasing
Two mechanisms may be responsible for maintenance of pathogens in a population
inbreeding depression and balancing selection It remains unclear if these animal studies have any relevance to human
Consanguinity has been implicated in susceptibility to a number of human diseases including heart disease, multiple sclerosis, depression and asthma
IntroductionIntroduction
In This First Study of its Kind in
HumansThey used microsatellite genome screen linkage
data for three infectious diseases in contrasting populations
tuberculosis in Gambia ,
hepatitis B both in Gambia and Italy and leprosy in India
To determine the extent of genomewide heterozygosity as an important predictor of susceptibility to some
diseases
Particularly in populations where inbreeding is common
Results
Strong association between consanguinity and human susceptibility to both TB and hepatitis B in West Africans
No significant association for hepatitis B in the Italians, probably due to the low levels of consanguinity
No significant association in the leprosy dataset in Indians, where the heterozygosity–heterozygosity correlations indicate similar levels of inbreeding in both cases and controls
Results
In two of three examples where a population has highlevels of consanguineous marriages, affected individuals reveal significant evidence of inbreeding compared with unaffected controls
Leprosy in India is an exception, as it thought to be strongly associated with two major effect loci /oligogenicity
Therefore, may be that persistent, strong inbreeding in the Indian populations has led to genetic purging
Correlations in heterozygosity among markers for affected and unaffected
individuals
A the entire datasetR affected family
%of consanguinity in each population is in brackets, * p>0.05, ** p>0.0009
stronger impact of consanguinity on
hepatitis than on TB
unaffected individuals yielded a higher
correlation than for affected individuals
Relationship between the strength of the heterozygosity and the proportion of inbred
individuals
second cousins
first cousins equal mixture
of the two
first-cousin marriages appear
necessary inorder to account
for the values observed in
Gambia
Consanguinity Management
Social awareness of consanguinity risks
Populations genetic screening
Counseling the youth
Warning who at risk
Conclusion