Co-introgression of Y-chromosome haplogroups and the sickle cell gene across Africa's Sahel.

The Sahel that extends from the Atlantic Ocean to the Ethiopian highland is a historical reservoir of Africa's cultures and grandest populations and a known arena of ancient and recent migrations. We are interested in the issue whether such migrations were also carriers of genetic traits and whether this introgression could be associated with population genetic markers. Based on analysis of Y-chromosome haplogroups, we present evidence that the sickle gene, one of the major protective polymorphisms known in malaria, has in fact found its way only recently to the gene pool of the populations in eastern Sahel. We discuss the possible dynamics of the process and give estimates of the age of the introduction of the S allele into eastern Sahel.

The mystery of Etruscan origins: novel clues from Bos taurus mitochondrial DNA.

The Etruscan culture developed in Central Italy (Etruria) in the first millennium BC and for centuries dominated part of the Italian Peninsula, including Rome. The history of the Etruscans is at the roots of Mediterranean culture and civilization, but their origin is still debated: local or Eastern provenance? To shed light on this mystery, bovine and human mitochondrial DNAs (mtDNAs) have been investigated, based on the well-recognized strict legacy which links human and livestock populations. In the region corresponding to ancient Etruria (Tuscany, Central Italy), several Bos taurus breeds have been reared since historical times. These breeds have a strikingly high level of mtDNA variation, which is found neither in the rest of Italy nor in Europe. The Tuscan bovines are genetically closer to Near Eastern than to European gene pools and this Eastern genetic signature is paralleled in modern human populations from Tuscany, which are genetically close to Anatolian and Middle Eastern ones. The evidence collected corroborates the hypothesis of a common past migration: both humans and cattle reached Etruria from the Eastern Mediterranean area by sea. Hence, the Eastern origin of Etruscans, first claimed by the classic historians Herodotus and Thucydides, receives strong independent support. As the Latin philosopher Seneca wrote: Asia Etruscos sibi vindicat (Asia claims the Etruscans back).

Worldwide human relationships inferred from genome-wide patterns of variation.

Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation.

The Himalayas as a directional barrier to gene flow.

High-resolution Y-chromosome haplogroup analyses coupled with Y-short tandem repeat (STR) haplotypes were used to (1) investigate the genetic affinities of three populations from Nepal--including Newar, Tamang, and people from cosmopolitan Kathmandu (referred to as "Kathmandu" subsequently)--as well as a collection from Tibet and (2) evaluate whether the Himalayan mountain range represents a geographic barrier for gene flow between the Tibetan plateau and the South Asian subcontinent. The results suggest that the Tibetans and Nepalese are in part descendants of Tibeto-Burman-speaking groups originating from Northeast Asia. All four populations are represented predominantly by haplogroup O3a5-M134-derived chromosomes, whose Y-STR-based age (+/-SE) was estimated at 8.1+/-2.9 thousand years ago (KYA), more recent than its Southeast Asian counterpart. The most pronounced difference between the two regions is reflected in the opposing high-frequency distributions of haplogroups D in Tibet and R in Nepal. With the exception of Tamang, both Newar and Kathmandu exhibit considerable similarities to the Indian Y-haplogroup distribution, particularly in their haplogroup R and H composition. These results indicate gene flow from the Indian subcontinent and, in the case of haplogroup R, from Eurasia as well, a conclusion that is also supported by the admixture analysis. In contrast, whereas haplogroup D is completely absent in Nepal, it accounts for 50.6% of the Tibetan Y-chromosome gene pool. Coalescent analyses suggest that the expansion of haplogroup D derivatives--namely, D1-M15 and D3-P47 in Tibet--involved two different demographic events (5.1+/-1.8 and 11.3+/-3.7 KYA, respectively) that are more recent than those of D2-M55 representatives common in Japan. Low frequencies, relative to Nepal, of haplogroup J and R lineages in Tibet are also consistent with restricted gene flow from the subcontinent. Yet the presence of haplogroup O3a5-M134 representatives in Nepal indicates that the Himalayas have been permeable to dispersals from the east. These genetic patterns suggest that this cordillera has been a biased bidirectional barrier.

Relationship of the sickle cell gene to the ethnic and geographic groups populating the Sudan.

The presence of a geographical pattern in the distribution of the sickle cell gene (S gene) and its association with malaria is well documented. To study the distribution of the S gene among various ethnic and linguistic groups in the Sudan we analyzed a hospital-based sample of 189 sickle cell anemia (SCA) patients who reported to the Khartoum Teaching Hospital between June 1996 and March 2000 and 118 controls with other complaints, against their ethnic and linguistic affiliations and geographic origin. Electrophoresis for hemoglobin S and sickling tests were carried out on all patients and controls as a prerequisite for inclusion. The majority of patients (93.7%) belonged to families of single ethnic descent, indicating the high degree of within-group marriages and thus the higher risk of augmenting the gene. SCA was found to be predominant among the Afro-Asiatic-speaking groups (68.4%) including nomadic groups of Arab and non- Arab descent that migrated to the Sudan in various historical epochs. Those patients clustered in western Sudan (Kordofan and Darfur) from where 73% of all cases originate. The proportion of patients reporting from other geographic areas like the south (3.1%), which is primarily inhabited by Nilo-Saharan-speaking groups (19% of the whole sample) who populated the country in previous times, is disproportionate to their total population in the country (chi(2) = 71.6; p = 0.0001). Analysis of the haplotypes associated with the S gene indicated that the most abundant haplotypes are the Cameroon, Benin, Bantu and Senegal haplotypes, respectively. No relationship was seen between haplotypes and the various hematological parameters in the sub-sample analyzed for such association. These results provide an insight into the distribution of the sickle cell gene in the Sudan, and highlight the strong link of the middle Nile Valley with West Africa through the open plateau of the Sahel and the nomadic cattle herders and also probably the relatively young age of the S gene.