Phuppi ki Beti, Mamoon ka Beta

Cousin marriages are very popular in Pakistan. Several studies from
Punjab estimate the prevalence of consanguineous marriages (defined as
marriages between blood relatives) at about 50%. There are distinct cultural
advantages in marrying a close relative. In a culture where most marriages
are arranged, and there is little chance to interact with members of the
opposite sex, for both partners, there is the comfort of familiarity. From
the boy's (literal translation of larka) parents, there is the hope that
since the daughter-in-law is a bhanji/bhatijee, there will not be much
resentment or conflict with them. For the girl's family, there is the reassurance
that their child is unlikely to be mistreated - an extremely important
consideration in a country where abuse of women is common. In some instances,
there are economic considerations - property remains within the family.

Cousin marriages, therefore, make sense in many ways. However, from
a population genetic standpoint, they may not be a prudent choice. Sexual
reproduction was designed for a reason - to produce genetic mixing and
diversity - as opposed to asexual reproduction practiced by bacteria and
amebae who simply divide themselves to produce identical daughter clones.
Why is genetic mixing important in higher organisms? A brief and simple
primer on human genetics follows.

For each genetic locus (excluding genes on X and Y chromosomes), we
inherit two copies (called alleles), one from each of our parents. If the
genes are the same, the offspring is homozygous for that allele, if they
are different - he/she is heterozygous. In most cases, as long as one of
the two genes is functional, normal human life is possible, and although
an individual may be a carrier of one defective gene, no overt disease
results, because the normal gene compensates to some extent. However, if
both genes are defective, disease does result. Because inbreeding increases
the frequency of homozygous genes, the offspring of consanguineous marriages
have an increased risk over that of the general population of having many
different types of diseases. The magnitude of risk depends on the frequency
of defective genes in the population and the degree of relationship between
the parents (an example will follow later).

The degree of inbreeding for the offspring of a particular couple can
be quantified by calculating the Coefficient of Inbreeding (F). The coefficient
measures the probability (genetics is a game of statistics) that a child
receives two alleles at a given locus that were both from the same ancestor
and are, thus, identical by descent. Some of these numbers are given below:

"Type of Mating" "Proportion of Shared Alleles" "F Value Between Couple"
----------------------------------------------- ---------------------------
First Cousins  &nbsp:  1/8  &nbsp:  1/16 (0.0625)
Double First Cousins  &nbsp:  1/4  &nbsp:  1/8 (0.125)
First Cousins Once Removed
(cousin, uncle/neice etc.)  &nbsp:  1/16  &nbsp:  1/32 (0.031)


In Punjab, the only area from which data is available, the average Coefficient
of Inbreeding is 0.029 (Shami et al. Journal of Biosocial Science, Jan
1994). What does this mean in real terms? Suppose that there is a defective
gene in the population that exists in a frequency of 1/200. If random mating
takes place (assuming Hardy-Weinberg Principles), the offspring's chance
of getting two defective genes are 1/40,000 (1/200X1/200). If however,
the parents are first cousins, the risk increases to 1/2977, a thirteen
fold increase (this risk is calculated from a modification of the Hardy-Weinberg
equation (Bronya Keats, Population Genetics, Principles and Practice of
Medical Genetics, calculation available on request). For the individual,
this may seem like a tolerable risk, given all the benefits of a cousin
marriage. However, for society as a whole, it means thousands of children
with a genetic disorder.

Are these just theoretical risks with no basis in fact? Quite the contrary.
Much data now exists to prove that the risks are real. In a study from
Norway (American J of Epidemiology, Mar '97) the investigators compared
approximately 7500 children born to two Pakistani parents (30% of whom
were consanguineous) to children born to Norwegian parents and found the
risk of birth defects to be increased by 39% in the Pakistani children
overall. They attributed 28% of these birth defects to consanguinity -
no increase in risk in children of non-consanguineous Pakistani parents
relative to the Norwegian population was found.

In another study done as part of the 1990/1991 Pakistan Demographic
and Health Survey, data were collected from approximately 26,000 births,
and the effects of consanguinity on mortality (while controlling for other
factors) measured (Annals of Human Genetics, Mar '97). Inbreeding at the
level of the first cousin exerted a significant adverse effect on survival
into childhood. A study from the Aga Khan University in Karachi, showed
a 40% increase in the incidence of low-birth weight babies in offspring
of related parents compared to babies born to non-related parents. The
Annals of Human Biology concluded that the widely favored practice among
Pakistanis, at home and abroad, of marriage between close relatives may
be a contributor factor in their comparatively unfavorable health profile.


Researchers in Europe and America have realized what a gold mine the
Pakistani population is - for identifying the basis of many genetic diseases.
Thalessemia, a disorder of hemoglobin production and anemia is the most
common one (approximately 1 in 25 individuals in Pakistan carries this
gene), but just a cursory search of recent literature identified a laundry
list of exotic sounding diseases (Combined Factor V-Factor VIII deficiency,
familial aplasia/hypoplasia of pelvis, non-syndromic deafness, retinitis
pigmentosa, muscular dystrophies and so on).

Since 50% or more of our genetic material is expressed in the brain,
it is logical to presume that consanguinity of parents may have subtle
neuro-developmental effects in their children. However, this has never
been studied in practice. Some neurobiologists have speculated that extensive
consanguinity among Muslim populations has led to the current decline of
the Muslim Ummah because our genetic pool is no longer healthy - even if
this has not resulted in obvious disease, it has affected us in subtle
ways. It would be interesting to use sophisticated tests that try to measure
if cognitive differences exist in the offspring of related versus unrelated
parents, in large populations, while controlling for confounding variables.

To summarize, the many advantages of cousin marriages are offset by
the potential biologic risk to the offspring. Cousin marriages should be
discouraged, especially in families where a lot of inbreeding has already
taken place in previous generations. Here again, the bottom line is - diversity
is good, homogeneity is bad!