Lactase persistence (LP), the state enabling the digestion of milk sugar in adulthood, occurs only in some human populations. The convergent and independent origin of this physiological ability in Europe and Africa is linked with animal domestication that either had started in both places independently or had spread from the Near East by acculturation. However, it has recently been shown that at least in its southern parts, the population of Arabia not only has a different LP-associated mutation profile than the rest of Africa and Europe but also had experienced an independent demographic expansion occurring before the Neolithic around the Pleistocene-Holocene boundary. In Arabia, LP is associated with tion -13,915G and not, as in Europe, with -13,910*T or, as in Africa, with -13,907^*G and -14,010^*C. We show here that, in Arabia, -13,915^*G frequency conforms to a partial clinal pattern and that this specific mutation has likely been spread from Arabia to Africa only recently from the sixth century AD onward by nomadic Arabs (Bedouins) looking for new pastures. Arabic populations in Africa that still maintain a nomadic way of life also have more -13,915^*G variants and fewer sub-Saharan L-type mitochondrial DNA haplogroups; this observation matches archaeological and historical records suggesting that the migration of Arabic pastoralists was accompanied by gradual sedentarization that allowed for admixture with the local African population.

Celiac disease (CD) is a multifactorial chronic inflammatory condition that results in injury of the mucosal lining of the small intestine upon ingestion of wheat gluten and related proteins from barley and rye. Although the exact mechanisms leading to CD are not fully understood, the genetic basis of CD has been relatively well characterized. In this review we briefly review the history of discovery, clinical presentation, pathophysiology, and current understanding of the genetics underlying CD risk. Then, we discuss what is known about the current distribution and evolutionary history of genes underlying CD risk in light of other evolutionary models of disease. Specifically, we conclude that the set of loci underlying CD risk did not cohesively evolve as a response to a single past selection event such as the development of agriculture. Rather, deterministic and stochastic evolutionary processes have both contributed to the present distribution of variation in CD risk loci. Selection has shaped some components of this network, but this selection appears to have occurred at different points in the past. Other parts of the CD risk network have likely arisen due to stochastic processes such as genetic drift.

The Rama Amerindians from southern Nicaragua are one of few indigenous populations inhabiting the east coast and lowlands of southern Central America. Early-eighteenth-century ethnohistorical accounts depicted the Rama as a mobile hunter-gatherer and horticulturalist group dispersed in household units along southern Nicaraguan rivers. However, during the nineteenth and twentieth centuries, Rama settlement patterns changed to aggregated communities because of increased competition for local resources resulting from nonindigenous immigration. The objective of this study was to discern the degree of relatedness between and within subdivisions of seven of these communities based on patterns of surname variation and genealogical data. We applied surname analyses (n = 592) to evaluate inter-and intrapopulation variation, consanguinity and substructure estimates, and isolation by distance and used a genealogically based marital migration matrix obtained during fieldwork in 2007 and 2009 to better understand internal migration. Our evaluation indicates a pattern of geographic distribution linking kinships in major subpopulations to nearby family-based villages. Mantel tests provide a correlation (r = 0.4;p < 0.05) between distance matrices derived from surname and geography among Rama communities. Genealogical analysis reveals a pattern of kin networks within both peripheral and central populations, consistent with previous genetic investigations, where the Amerindian mitochondrial DNA haplogroup B2 is commonly found among peripheral communities and A2 is frequent in central subpopulations. Marital migration and genealogies provide additional information regarding the influx of non-Ramas to communities near populated villages. These results indicate that the disruption of the Rama's traditional way of life has had significant consequences on their population structure consistent with population fissions and aggregations since the eighteenth century.

On thinking quantitatively of complex diseases, there are at least three statistical strategies for association studies: one single-nucleotide polymorphism (SNP) on a single trait, gene or region (with multiple SNPs) on a single trait, and gene or region on multiple traits. The third approach is the most general in dissecting genetic mechanisms underlying complex diseases underpinning multiple quantitative traits. Gene or region association methods based on partial least square (PLS) approaches have been shown to have apparent power advantage. However, few approaches have been developed for multiple quantitative phenotypes or traits underlying a condition or disease, and the performance of various PLS approaches used in association studies for multiple quantitative traits have not been assessed. Here we exploit association between multiple SNPs and multiple phenotypes or traits, from a regression perspective, through exhaustive scan statistics (sliding window) using PLS and sparse PLS regressions. Simulations were conducted to assess the performance of the proposed scan statistics and compare them with existing methods. The proposed methods were applied to 12 regions of genome-wide association study data from the European Prospective Investigation of Cancer-Norfolk study.

Previous studies identified a cluster of individuals with an autosomal recessive form of deafness that reside in a small region of mid-Michigan. We hypothesized that affected members from this community descend from a defined founder population. Using public records and personal interviews, we constructed a genealogical database that includes the affected individuals and their extended families as descendants of 461 settlers who emigrated from the Eifel region of Germany between 1836 and 1875. The genealogical database represents a 13-generation pedigree that includes 27,747 descendants of these settlers. Among these descendants, 13,784 are presumed living. Many of the extant descendants reside in a 90-square-mile area, and 52% were bom to parents who share at least one common ancestor. Among those bom to related parents, the median kinship coefficient is 3.7 × 10 ^-3. While the pedigree contains 2,510 founders, 344 of the 461 settlers accounted for 67% of the genome in the extant population. These data suggest that we identified a new population isolate in North America and that, as demonstrated for congenital hearing loss, this rural mid-Michigan community is a new resource to discover heritable factors that contribute to common health-related conditions.