Consanguinity >>> susceptibility to infectious diseases

1. Consanguinity
Advanced Topics in
Genomics
6-10-2011
Prof. Moein Kanaan
Amer Wazwaz

2. Consanguinity is a term, derived from two Latin words
con " meanscommon , orof the same and "sanguineus " meansblood"
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

3. Introduction
Little 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
of the global population are related as second cousins or 10.4%
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

4. The Current Global Prevalence of
Consanguineous Marriage
Consanguinity rates vary from one population to another depending
on religion, culture and geography
Global distribution of marriages between couples related as second cousins or closer

5. Consanguinity Rates in Arab Populations
1C<
Double first-cousin
marriage
1C
First-cousin
marriage
Source: Tadmouri G.O et al, Reproductive Health .2009

6. Consanguinity Extent and Complexity
Influences and outcomes of consanguineous marriages

7. 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

8. 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 theclan or its hereditary equivalent
may be the most logical unit for genetic screening

9. Influence of Consanguinity on
Complex Diseases
Consanguinity expected to exert a greater influence on
the complex diseases ifrare 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
for Breast Cancer and Hypertensionve-

10. 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 studyexamined
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

11. Comparative mortality in first cousin versus non-
consanguineous progeny in 69 study populations
mean excess
mortality at
first-cousin
level of 3.5%
1C first cousin NC non-consanguineous

12. Consanguinity and Susceptibility to
Infectious Diseases 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
fortuberculosis ,hepatitis and
leprosy, used to test the
hypothesis that inbreeding
depression increases risk of
infection

13. Introduction
Studies link between genetic diversity and disease
susceptibility are increasing
Two mechanisms may be responsible for maintenance of
pathogens in a population
inbreeding depression andbalancing 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 includingheart disease,
multiple sclerosis ,depression andasthma

14. In This First Study of its Kind in
Humans
They used microsatellite genome screen linkage data for
three infectious diseases in contrasting populations
,tuberculosis inGambia
hepatitis B both inGambia andItaly
and leprosy inIndia
To determine the extent of genomewide heterozygosity as
an important predictor of susceptibility to some diseases
Particularly in populations where inbreeding is common

15. 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

16. Results
In two of three examples where a population has high
levels 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

17. Correlations in heterozygosity among markers
for affected and unaffected individuals
A the entire dataset
R affected family
stronger impact of
consanguinity on hepatitis
than on TB
unaffected individuals
yielded a higher correlation
than for affected
individuals
,** p>0.0009of consanguinity in each population is in brackets, * p>0.05 %

18. 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 in
order to account
for the values
observed in Gambia

19. Conclusion
Consanguinity Management
Social awareness of consanguinity risks
Populations genetic screening
Counseling the youth
Warning who at risk