There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F ≥ 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ≈3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates. community genetics | inbreeding | reproduction | health | social structure

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BackgroundThe anaerobic spirochete Brachyspira pilosicoli colonizes the large intestine of various species of birds and mammals, including humans. It causes “intestinal spirochetosis”, a condition characterized by mild colitis, diarrhea and reduced growth. This study aimed to sequence and analyse the bacterial genome to investigate the genetic basis of its specialized ecology and virulence.Methodology/Principal FindingsThe genome of B. pilosicoli 95/1000 was sequenced, assembled and compared with that of the pathogenic Brachyspira hyodysenteriae and a near-complete sequence of Brachyspira murdochii. The B. pilosicoli genome was circular, composed of 2,586,443 bp with a 27.9 mol% G+C content, and encoded 2,338 genes. The three Brachyspira species shared 1,087 genes and showed evidence of extensive genome rearrangements. Despite minor differences in predicted protein functional groups, the species had many similar features including core metabolic pathways. Genes distinguishing B. pilosicoli from B. hyodysenteriae included those for a previously undescribed bacteriophage that may be useful for genetic manipulation, for a glycine reductase complex allowing use of glycine whilst protecting from oxidative stress, and for aconitase and related enzymes in the incomplete TCA cycle, allowing glutamate synthesis and function of the cycle during oxidative stress. B. pilosicoli had substantially fewer methyl-accepting chemotaxis genes than B. hyodysenteriae and hence these species are likely to have different chemotactic responses that may help to explain their different host range and colonization sites. B. pilosicoli lacked the gene for a new putative hemolysin identified in B. hyodysenteriae WA1. Both B. pilosicoli and B. murdochii lacked the rfbBADC gene cluster found on the B. hyodysenteriae plasmid, and hence were predicted to have different lipooligosaccharide structures. Overall, B. pilosicoli 95/1000 had a variety of genes potentially contributing to virulence.Conclusions/SignificanceThe availability of the complete genome sequence of B. pilosicoli 95/1000 will facilitate functional genomics studies aimed at elucidating host-pathogen interactions and virulence.

Mate choice among early human groups and in many historical populations was subject to both demographic and social constraints, ensuring that most unions were between couples who had coinherited substantial proportions of their genomes from common ancestors. Even in populations in which close consanguineous marriage was proscribed, community endogamy would have been sufficient to ensure high levels of homozygosity. Consanguineous marriage remains the choice of an estimated 10.4% of the global population, although there has been an overall decline in its popularity, especially in developed countries. Recent studies have indicated that the shift from consanguineous marriage to panmixia has been accompanied by a reduction in homozygosity. The concomitant predicted decrease in incidence of both recessive single-gene disorders and more common adult-onset diseases will have a significant impact on the health of future generations.

Thalassaemia and sickle cell disease have been recognized by the World Health Organization as important inherited disorders principally impacting on the populations of low income countries. To create a national and regional profile of b-thalassaemia mutations in the population of India, a meta-analysis was conducted on 17 selected studies comprising 8,505 alleles and offering nearnational coverage for the disease. At the national level 52 mutations accounted for 97.5% of all b-thalassaemia alleles, with IVSI-5(G[C) the most common disease allele (54.7%). Population stratification was apparent in the mutation profiles at regional level with, for example, the prevalence of IVSI-5(G[C) varying from 44.8% in the North to 71.4% in the East. A number of major mutations, such as Poly A(T[C), were apparently restricted to a particular region of the country, although these findings may in part reflect the variant test protocols adopted by different centres. Given the size and genetic complexity of the Indian population, and with specific mutations for b-thalassaemia known to be strongly associated with individual communities, comprehensive disease registries need to be compiled at state, district and community levels to ensure the efficacy of genetic education, screening and counselling programmes. At the same, time appropriately designed community-based studies are required as a health priority to correct earlier sampling inequities which resulted in the under-representation of many communities, in particular rural and socioeconomically under-privileged groups.