Consanguineous marriages and endemic malaria: can inbreeding increase population fitness?

<p>Abstract</p> <p>Background</p> <p>The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of α⁺-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. The aim of this study was to explore the overall effects of inbreeding on the fitness of a population infested with malaria.</p> <p>Methods</p> <p>In a stochastic computer model of population growth, the sizes of inbred and outbred populations were compared. The model has been previously validated producing results for inbred populations that have agreed with analytical predictions. Survival likelihoods for different α⁺-thalassemia genotypes were obtained from the odds of severe forms of disease from a field study. Survivals were further estimated for different values of mortality from malaria.</p> <p>Results</p> <p>Inbreeding increases the frequency of α⁺-thalassemia allele and the loss of life due to homozygosis of recessive lethal alleles; both are proportional to the coefficient of inbreeding and the frequency of alleles in population. Inbreeding-mediated decrease in mortality from malaria (produced via enhanced α⁺-thalassemia frequency) mitigates inbreeding-related increases in fatality (produced via increased homozygosity of recessive lethals). When the death rate due to malaria is high, the net effect of inbreeding is a reduction in the overall mortality of the population.</p> <p>Conclusion</p> <p>Consanguineous marriages may increase the overall fitness of populations with endemic malaria.</p

Breast cancer protection by genomic imprinting in close kin families

Abstract Human inbreeding generally reduces breast cancer risk (BCR). When the parents are biologically related, their infants have a lower birth weight due to smaller body organs. The undersized breasts, because of fewer mammary stem cells, have a lower likelihood of malignant conversion. Fetal growth is regulated by genomically imprinted genes which are in conflict; they promote growth when derived from the father and suppress growth when derived from the mother. The kinship theory explicates that the intensity of conflict between these genes affects growth and therefore the size of the newborn. In descendants of closely related parents, this gene clash is less resulting in a smaller infant. In this review, we elucidate the different mechanisms by which human inbreeding affects BCR, and why this risk is dissimilar in different inbred populations

Genetic Benefits of Consanguinity Through Selection of Genotypes Protective Against Malaria

Consanguineous marriages are usually socially driven and can be genetically harmful. The detrimental effects of inbreeding are the consequence of homozygosity of harmful genes. On the other hand, beneficial effects of inbreeding, theoretically, could be expected in those who are homozygous for protective recessive and codominant genes. Here, we argue that the most common monogenetic conditions in humans, namely, α-thalassemia, glucose-6- phosphate dehydrogenase (G6PD) deficiency, hemoglobin C, and Duffy antigen negative red blood cells, which have evolved under pressure from malaria, had their survival and selection enhanced by consanguineous marriages in malaria-infested regions of the world. This hypothesis is supported by several observations. First, the presence of two mutations in homozygotes involving the listed conditions (except G6PD deficiency) imparts better protection against malaria than the presence of one or no mutation (heterozygous or normal genotypes, respectively); consanguinity increases the number of homozygotes, especially at low allele frequency. For G6PD deficiency, inbreeding could increase the allele frequency of the G6PD-deficient allele. Second, there is overlap between, on the one hand, the geographic distributions of malaria, thalassemias, and other red blood cell conditions that protect against malaria and, on the other hand, consanguineous marriages. Third, the distribution of different intensities of malaria infestation is matched with the frequency of human inbreeding. These observations, taken together, offer strong support to the hypothesis that the culture of consanguineous marriages and the genetics of protection against malaria have co-evolved by fostering survival against malaria through better retention of protective genes in the extended family

Kin and non-kin marriages and family structure in a rich tribal society

Human consanguinity is often attributed to poverty, lack of education and social insecurity. Nevertheless, kin unions continue to be arranged in socioeconomically transformed societies. This study examined the structure of families and marriages in the rich tribal society of the United Arab Emirates, which has had a high gross domestic product for the last two generations and currently has one of the highest in the world. The respondents were 217 national medical students whose families are proportionally distributed to the population of the country emirates. The rate of parental consanguinity (defined as a union of any two cousins) was 36%. The social status and mean size of consanguineous and non-consanguineous families were not significantly different. In non-consanguineous families, polygamy was more common and the number of half-siblings per family was higher. The extended families were on average 7% larger among non-consanguineous families. In contrast, for the extended families of the participants' grandparents, non-consanguineous families were smaller than their consanguineous counterparts. Participants from consanguineous families indicated that marriage of either a son or daughter was more difficult to arrange than did participants from non-consanguineous families. Though consanguineous parents had their offspring marry consanguineously more often than non-consanguineous parents, the numbers of married offspring in the two groups of families were not different. Consanguineous parents have more difficulty than non-consanguineous parents in finding spouses for themselves and for their offspring, and they arranged kin marriages for their children more often

Selection of kin for spouse: Importance of socioeconomic status, reputation and beauty

Objectives: Kin marriages are often arranged in societies with many kinship groups and this is believed to be related to poverty and associated lack of education and security. We examined (i) whether choice of kin for spouse was affected by the improved socioeconomic and security conditions, and (ii) compare relative importance of family reputation vs. family wealth and social status and physical appearance in selection of future spouse. Methods: In an electronic survey, 268 Emirati medical students were asked to provide information about their families, biological relation to preferred future spouse and rank the importance of family reputation, family wealth, family social status, and physical appearance in selecting a future spouse. Frequency of kin marriages in two generations was examined within the context of socioeconomic development of the nation. Results: Kin marriage rate among parents (36.4%, 79/217) and likely future rate among their children (31.4%, 37/118) were similar (p = 0.35). Awareness of harms of inbreeding had a small but statistically significant deterring effect on selecting kin for spouse. The respondents ranked family reputation (72.2%) as most important in comparison to that for the family wealth (5.6%) and social status (9.2%) and spouse physical attractiveness (13.0%). However, family reputation was equally important for the participants with different preferences of kin and non-kin for spouse (p = 0.57). Conclusions: The frequency of kin marriages in studied population did not change significantly in the last generation. Knowledge of biological harm of inbreeding has only a small inhibitory effect on choice of kin for spouse. Family reputation was far more important in selection of spouse than family wealth, social status and beauty of spouse, but reputation was uncorrelated with choice of kin for spouse

The survivals of the three genotypes used in this simulation are shown in the lower part of graph at the intersections with vertical lines which point to the results in the upper part of graph

The ratio of differential survival of genotypes = (- )/(- ).<p><b>Copyright information:</b></p><p>Taken from "Consanguineous marriages and endemic malaria: can inbreeding increase population fitness?"</p><p>http://www.malariajournal.com/content/7/1/150</p><p>Malaria Journal 2008;7():150-150.</p><p>Published online 2 Aug 2008</p><p>PMCID:PMC2527611.</p><p></p

In the upper panel, initial negative excess of relative fitness (blue bars) in the inbred population is the effect of recessive lethal alleles

An excess of α-thalassemia allele (red bars) is seen after 5–6 generations – after allele frequency (black S-shape line) is increased to around 0.2. Relative excess of α-thalassemia is maximal when its frequency is in the middle of the range (~0.35–0.7). Results are for = 1000 and the ratio of differential survival = 1.39. In the lower panel, the calculated relative fitness includes only the effect of α-thalassemia. The fitness ratio is the size of inbred population divided with that of outbred population. The results are for → ∞ and the ratio of differential survival = 1.39.<p><b>Copyright information:</b></p><p>Taken from "Consanguineous marriages and endemic malaria: can inbreeding increase population fitness?"</p><p>http://www.malariajournal.com/content/7/1/150</p><p>Malaria Journal 2008;7():150-150.</p><p>Published online 2 Aug 2008</p><p>PMCID:PMC2527611.</p><p></p