Monday, 11 August 2008

Consanguineous marriages prevent malarial deaths

August 11, 2008
By Syed Akbar
Consanguinity or marriage between close relation has always been associated with genetic disorders and high mortality rate in children born out of such wedlock. While geneticists world-wide are discouraging people from marrying their close relatives, a scientific study on the effect of consanguinity on malarial deaths reveals that this ancient practice, in fact checks mortality rate in places where malaria is highly endemic.
Incidentally, the he practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of alpha thalassemia, which is protective against malaria. However, it also causes an excessive mortality amongst the offspring due to an increase in homozygosis of recessive lethal alleles. But when one measures the benefits of reduction in
overall malarial deaths against the genetic disorders, the practice of consanguinity has to be encouraged in malaria endemic regions.
The study was carried by a team of scientists at UAE University, Abu Dhabi. According to Mukesh M Agarwal, one of the researchers, they had selected a computer model of population growth and compared the sizes of inbred and outbred populations. The team obtained the survival likelihood for different alpha thalassemia genotypes.
"Human inbreeding enhances the speed of fixation of recessive and codominant alleles. Consequently, the elimination of recessive lethal alleles is increased by an excessive mortality of children in consanguineous populations.
However, an enhanced speed of selection of the codominant alpha thalassemia allele in such inbred populations increases the relative fitness against malaria. When
mortality from malaria is high, this increase in fitness could offset the loss of life resulting from inbreeding. Therefore, consanguinity augments the fitness of a population with endemic malaria through its effect on alpha thalassemia allele," the study pointed out.
When the death rate due to malaria is high, the net effect of inbreeding is a reduction in the overall mortality of the population. Consanguineous marriages may increase the overall fitness of populations with endemic malaria.
Interestingly, marriages between close biological relatives account for up to 60 per cent of all marriages in many parts of Asia, Middle East and Africa. A common finding among consanguineous populations is their long history of exposure to malaria. In fact, the frequency and degree of consanguineous marriages correlates with the geographic distribution and intensity of Plasmodium falciparum in the population.
Alpha thalassemia has become the most common monogenic disorder in humans potentially because it decreases the probability of death from infection with P. falciparum.
The UAE team restricted their study model to exclusively large populations as the effect of inbreeding on the selection of recessive and codominant alleles is significantly less in smaller populations.
Additionally, when malaria emerged as an epidemic infection 4,000 to 10,000 years ago, the agrarian revolution had already caused a population explosion, an epidemiological pre-requisite for the appearance of malaria as an epidemic infection.
Mortality from Plasmodium falciparum is the highest in the first five years of life and it decreases with subsequent infections. During a single epidemic, malaria can kill up to 50 per cent of a susceptible population.
When the mortality from malaria is low, consanguinity depresses the population with alpha thalassemia by causing an excessive number of deaths via recessive lethal alleles and by negligibly retarding the selection of alpha thalassemia allele.
"More consanguineous marriages should be encouraged to take place among alpha thalassemia-carrier families. Even in non-carrier families, consanguinity may not be discouraged despite its genetic dangers (like childhood deaths and increased congenital malformations). This is because for any specific morbidity to be noticed, the difference from the reference (non-consanguineous, in this case) has to be sufficiently higher than five per cent, but is generally much below this threshold,"
he said.
The UAE study also corroborates findings from India which has over 50,000 brotherhoods and the frequency of alpha thalassemia is higher in tribal than in city populations. In the pas, when human survival became adversely affected by malaria, intra-family unions resulted inbetter survival of the offspring.
"In our globalised world with greater than ever mixing of populations, diseases like tuberculosis and AIDS are still the leading causes of death. Protection against both is provided by codominant and recessive alleles, whose selection could be accelerated by inbreeding," the scientists suggested.

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