Sickle Cell Disease by the HbS haplotype

HbS of African derivation...some parties almost always associate its presence in non-African locations, or else what is perceived to be "non-Sub-Saharan" Africa locations, with historic slavery. How accurate is this observation?

Before one gets into the details about the issue of legitimacy of the above mentioned perception, it is perhaps necessary to know some basic things about HbS:

It is essentially an altered beta-globin (b-globin) cluster of the Hemoglobin A, a cluster which is located at position 15.5 away from the centromere of chromosome 11 on its short arm; the specific alteration that gives rise to HbS instead of the "normal" HbA, is a "point mutation" [*1] in GAC codon at position 6 of the b-globin cluster, which converts GAC to GTG, resulting in the replacement of glutamic acid amino acid by valine. Several haplotypes are associated with this mutation; there are supposed to be some 475 identified allele variants of the b-globin gene, of which the HbS haplotypes are a subset. This includes the African derivatives, namely; the Senegalese, Benin and Bantu haplotypes. Outside of African derivatives, there is the Asian haplotype, mainly found in Arabia and the Indian sub-continent.

Now, since it is difficult to age HbS variants with respect to one another, due to selective pressure acting on the extent of its availability, the distribution pattern becomes worthy of noting, as well as geographical origin. Apparently, the African haplotypes have the highest prevalence among African subjects and recent African descendants. Of the African variants, the Benin haplotype appears to have wider geographical reach, perhaps because it originated in the vicinity of the Niger River Valley, and spread through ancient contact in the Sahara. So, treating African HbS haplotypes unanimously as the product of slave trade is not only simplistic, but also erroneous. Consider the fact for example, that there are locations where African slaves had historically been brought as "pick up points" for trade between the trading parties, after having been picked up from their home region in some other geographical location, but are nonetheless virtually free from the sickle cell disease; the African Horn comes to mind as an example, and yet HbS has hardly penetrated that region. Some may be tempted to attribute this phenomenon to the environment of that region, but that assessment would be oblivous to the fact that Bantu-speaking populations neighbouring the populations of these regions, have high prevalence cases of HbS variants [i.e. Bantu haplotype]. This point is especially relevant, when its presence in Egypt is merely explained off as the product of that region being a historic corridor for slave trade. Additionally, it is necessary to note documented cases of HbS outside of sub-Saharan Africa, in order to realize that the antiquity of its heritage in those regions precedes historic slave trade involving slaves brought from sub-Saharan Africa. For examples, we have the following:

Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease.

el-Hazmi MA, Warsy AS, Bashir N, Beshlawi A, Hussain IR, Temtamy S, Qubaili F.Medical

Biochemistry Department, World Health Organization Collaborating Centre for Haemoglobinopathies, Thalassaemias and Enzymopathies, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

Objective
This study was conducted with two objectives: to determine the b-globin gene haplotypes associated with Hb S in Arabic-speaking populations from different countries (Egypt, Syrian Arab Republic and Jordan), and to compare the results with those of Saudi SCD patients from different regions of Saudi Arabia, where both mild and severe forms of the disease exist.

Patients and methods
The study group of 126 SCD patients comprised 14 Egyptians, 9 Syrians, 10 Jordanians and 93 Saudis. Some of the Egyptians, Syrians and Jordanians were living in Riyadh, while others were living in their own countries, from where buffy coats were received. The Saudis were from three areas of Saudi Arabia where the sickle-cell gene has been reported at a high frequency, these being eastern (22 patients), south-western (67) and north-western (4) regions...

Buffy coat was used to extract DNA [18]. Portions of DNA were first subjected to polymerase chain reaction (PCR) amplification, and the PCR product was restricted using Ava II, HindIII, HincII, Hpa I and Xmn I, following the procedure published earlier [19,20]. The presence or absence of each site (shown in Figure 1) was identified, based on the size of the fragments produced (Table 1).

Results
"We collaborated with researchers from Egypt, Syrian Arab Republic and Jordan in a study of patients with sickle-cell disease from those countries, and from various parts of Saudi Arabia, in order to investigate the influence of genetics on the clinical presentation of the disease, and to attempt to determine the **origin** of the sickle-cell gene in Arabs. Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there are at least two major foci for the origin of the sickle-cell gene, one in the eastern part of Saudi Arabia, and the other in the populations of North Africa and the north-western part of the Arabian peninsula…

The Benin haplotype was found in patients with severe disease, either as homozygous or in combination with another haplotype. The majority of Syrians and Jordanians had the Benin haplotype, and severe disease. However, one in three Syrians and one in five Jordanians had a milder disease, and the Saudi-Indian haplotype was identified.

All Saudi patients from south-western and north-western areas, where the disease is generally severe, had the Benin haplotype in the homozygous or heterozygous state. Of the Saudi patients from the eastern area, where a mild form of SCD exists, only 9% had the Benin haplotype. The remainder had the Saudi-Indian haplotype, either in its homozygous or heterozygous state…

Restriction endonuclease restriction sites have provided a useful insight into the normal polymorphic variations in the DNA surrounding various gene loci, where a combination of two or more polymorphic sites has led to the identification of specific haplotype patterns [13,14]. This has been of significance in the study of the regions surrounding the b-globin gene (i.e. the b-globin gene cluster), where several polymorphic sites have been identified, and population differences have been found on analysis of the haplotype pattern [9]. An interesting observation is that the sickle-cell mutation has occurred on chromosomes carrying different polymorphic sites and different b-globin gene haplotypes, and this seems to play a role in the clinical expression of SCD [9].

We compared the haplotype pattern of SCD patients from different Arabic-speaking countries. Benin haplotype was the major haplotype in all countries with a severe presentation of SCD and it was present in both the homozygous and heterozygous state. This was true for those SCD patients from south-western and north-western areas of Saudi Arabia, and for those from Egypt, Jordan and Syrian Arab Republic. On the other hand, patients from the eastern part of Saudi Arabia, who present with a significantly milder clinical picture, carried the Saudi-Indian b-globin gene haplotype either in its homozygous or heterozygous state."

Source: East Mediterr Health J. 1999 Nov;5(6):1154-8 http://www.emro.who.int/Publications/EMHJ/0506/10.htm

From the above, one gets the impression that the Benin haplotype is dominant over the other haplotypes wherein it appears in a heterozygous case. Not sure how that specifically goes on a case by case basis, wherein the Benin haplotype would appear with the other African variants, but at the least, this study demonstrates that it is the more likely dominant haplotype over that of the Asian haplotypes; the present author takes this to be the case [with the understanding that from the African side, only the Benin haplotype has notably penetrated the regions under discussion, while the others mentioned are of the Asian type], because it has always been identified with the severe cases of SCD in not only the homozygous cases, but also in the heterozygous cases...that is to say, what are the chances of heterozygous cases, especially in areas like eastern Saudi where the Asian haplotype is the prevalent HbS haplotype, being inclusive of Benin-Asian haplotype pairings? Quite likely—albeit to varying degrees, notwithstanding the discernable distribution patterns of these haplotypes as mentioned in the study. On the other hand, as noted, and to reiterate:

one in three Syrians and one in five Jordanians had a milder disease, and the Saudi-Indian haplotype was identified.

...this even when it occurred in either homozygous or heterozygous cases, not involving the Benin haplotype [which consistently appeared in severe cases of SCD, regardless of whether it was a heterozygous or homozygous case].

Another noteworthy case, is that SCD appears in the remains of predynastic subjects, and the only HbS haplotype noted in Egypt today is the Benin haplotype. As we will shortly see, the Benin haploype also accounts for all the known HbS cases outside of Africa, save for the Asian haplotype, largely confined to eastern Saudi Arabia and the Indian sub-continent.

Use of the amplification refractory mutation system (ARMS) in the study of HbS in predynastic Egyptian remains.

Marin A, Cerutti N, Massa ER.

1999 May-Jun

Dipartimento di Biologia Animale e dell'Uomo, Università degli Studi di Torino.

We conducted a molecular investigation of the presence of sicklemia in six predynastic Egyptian mummies (about 3200 BC) from the Anthropological and Ethnographic Museum of Turin. Previous studies of these remains showed the presence of severe anemia, while histological preparations of mummified tissues revealed hemolytic disorders. DNA was extracted from dental samples with a silica-gel method specific for ancient DNA. A modification of the polymerase chain reaction (PCR), called amplification refractory mutation system (ARMS) was then applied. ARMS is based on specific priming of the PCR and it permits diagnosis of single nucleotide mutations. In this method, amplification can occur only in the presence of the specific mutation being studied. The amplified DNA was analyzed by electrophoresis. In samples of three individuals, there was a band at the level of the HbS mutated fragment, indicating that they were affected by sicklemia. On the basis of our results, we discuss the possible uses of new molecular investigation systems in paleopathological diagnoses of genetic diseases and viral, bacterial and fungal infections.

PMID: 11148985 [PubMed - indexed for MEDLINE]

The interesting thing about the study, is that it too talks of severe cases of SCD, which as we've just seen, is the case with the Benin haplotype as well, and it takes us to a period that precedes any known documentation of slave trade involving sub-Saharan Africans.

Let's take a look at the distribution pattern and type of HbS haplotypes present in global samples:

The Benin haplotype accounts for HbS associated chromosomes in Sicily,4 Northern Greece,10 Southern Turkey,11 and South West Saudi Arabia,6,7 suggesting that these genes had their origin in West Africa. The Asian haplotype is rarely encountered outside its geographic origin because there have been few large population movements and Indian emigrants have been predominantly from non HbS containing populations. However, it is of interest that the Asian haplotype was first described among descendants of Indian indentured laborers in Jamaica.12 — Graham R. Serjeant, MD, FRCP, MRC Laboratories (Jamaica), University of the West Indies, Kingston.

The African type in the above regions appear to be exclusively the Benin haplotype, in contrast to...

From these original foci of the HbS mutation, the gene spread along trading routes to North Africa and the Mediterranean, was transported in large populations to North and South America and the Caribbean during the slave trade, and latterly has spread to Northern Europe by immigration from the Caribbean, directly from Africa to the United Kingdom, France, Belgium, and Holland, and from Turkey to Germany. The relative prevalence of these haplotypes in the Americas reflects the different origins of their African peoples, approximately 70% of HbS associated chromosomes having the Benin haplotype, 10% Senegal and 10% Bantu. Haplotype frequencies in Jamaica are similar to the USA but the Bantu haplotype accounts for the majority of HbS associated chromosomes in Brazil.9 — Graham R. Serjeant, MD, FRCP, MRC Laboratories (Jamaica), University of the West Indies, Kingstom.

It is of no coincidence that the other African haplotypes outside of the Benin haplotype, have found their way into the Americas, regions that have been affected by the historic slave trade, and have large size settler populations of recent common ancestry from sub-Saharan Africa.

What all these show, when taken together, is that blanket attribution of African HbS variants solely to historic slave trade events is a blatant distortion of reality.

Ps - A good map showing the geographical range of HbS haplotype variants:

P2 Clades: The Arrival of E3a and E3b Haplogroups

The MAJOR PN2 CLADES - E3a and E3b haplogroups: Investigating the backdrop against which they came about.

Recently, it has been proposed that E3b originated in sub-Saharan Africa and expanded into the Near East and northern Africa at the end of the Pleistocene (Underhill et al. 2001). - Cruciani et al. 2004, Phylogeographic analysis of haplogroup E3b...

We hear much about E3b and E3a haplogroup bearing populations in Africa, the major haplogroups on the African landscape today, but when and where did these lineages likely come about?

Here is what the present author of the blog thinks occurred, based on the information available to the author:

Between 23 and 18ky ago—Ogolian period begins, which coincides with and is likely connected to the LGM weather situation.

23,000 BP ~ 21,050 BC: "After a favourable climatic period, characterised by relatively dense and diversified Palaeolithic occupations, the arid Ogolian begins locally around 23000 years BP and is represented at Ounjougou by a significant depositional and archaeological hiatus." — Aziz Ballouche [see: Link ]

—Much of North Africa and the Sahara are characterized by adverse weather conditions, with much of the region turning arid. The Sahara at this time, extends south beyond its current boundaries to a certain point, possibly a little beyond the Niger bend.

Arid conditions extend all the way to the "horn" coast of the African Horn region, possibly encouraging populations to reside more inwards—away from that horn-shaped coastal region; rather, likely towards the region straddling southern Sudan, Ethiopia, Kenya and Uganda or even further—region straddling Uganda, Kenya, and Tanzania.

—PN2 clade (E3) bearers in the vicinity of the Sudanese-Central African Republic -Ugandan-Kenyan region give rise to E3a ~ between 21 and 18 ky ago [pending additional or new info]; E3b-M35* would have likely arose relatively earlier than E3a* [as evidenced by its near absence in some the populations that carry this], sometime prior to the Ogolian and the LGM period. At this time, it was likely the M78 derivative that came about ~ between 19 and 15 ky ago. It was also likely during this period, that some E3b-M35 variants spilled over to the "southwest Asia", which would be identified as E-M34. The E-M78* likely arose somewhere in the bidirectional-migration route between Northeast and sub-Saharan East Africa; this location was likely in the region straddling upper Egypt and Sudan of the eastern Sahara, amongst earlier E-M35 migrants from sub-Saharan East Africa. These M78 bearers were increasingly pressured to move further south due to progressive aridity, possibly as far as Uganda-Kenya and/or Tanzanian general region.

—The E3a bearing group would proceed westward, perhaps meeting groups of earlier lineages at the Shum Laka region of Cameroon, whereby quartz micro-lithic culture had already been in place by around 30 ky ago, hence preceding the rise of E3a common recent ancestor. But this group wouldn’t stay put here, at least not every section of it; they’d proceed to the savanna, grassland or vegetation holdouts in West Africa beyond the then boundaries of the Sahara. This probably occurred some time between 15ky and 13ky ago. During this period, as the Saharan aridity began to gradually slacken, some E-M78 bearing proto-Afrasan speaking nomads likely made their way into the Levant via the Sinai corridor.

Others taking refuge in the Cameroonian savanna-tropical forest general region probably followed suit, that is—after the aforementioned initial batch of migrants [bearing E3a descendants]; or else, the same group of people [from the initial migrants] shifted locations along the west African vegetation belts, once it became apparent that the far western reaches didn’t have much to offer, but the water system [as part of the Niger River]—however relatively shallow or what not—offered something additional. Finally, when the conditions in the Sahara were turning around for the better, starting between ~ 12ky and 11ky ago, these migrants would proceed northward, leaving the sort of trails that find expression at Ounjougou—Mali.

10th millennium BC ~ 12ky ago: At Ounjougou—"It is not until the Holocene and the return of humid climatic conditions, beginning in the 10th millennium BC, that it is possible to again observe evidence of human occupation." — Aziz Ballouche [see: Link ]

"Consequently, it has to be seen in the context of heavy rainfalls and a resettlement of the vegetation cover, during the 10th millennium BC, that a new population arrives on the Plateau of Bandiagara." — Human population and paleoenvironment in West Africa [see: Link ]

And...

From 30,600 to 10,000 BC: "A cultural flow, from the southeast of Subsaharan Africa and to the Sahara, could explain the diffusion of the microlithic industries all the way through West Africa. We observe them initially in Cameroon at Shum Laka (30.600-29.000 BC), then at the Ivory Coast in Bingerville (14.100-13.400 BC), in Nigeria in Iwo Eleru (11.460-11.050 BC), and finally in Ounjougou (phase 1, 10th millennium BC)." — Human population and paleoenvironment in West Africa [see: Link ]

It's very probable that this E3a bearing group(s) came into contact with the then wandering earlier-inhabitants of west Africa, who would have been pressured to move southward beyond the then Saharan desert boundaries, due to progressing aridity of the Ogolian period. These groups could have brought their central-Saharan pottery [e.g. found in Niger] traditions with them [developed perhaps sometime during the transitioning period to the wetter phase of the Sahara], just as the E3a bearing group(s) brought the microlithic traditions that they possibly picked up in the vicinity of the Shum Laka region [see above excerpt carbon dating estimations of finds] …and/or else…the new migrants produced their own versions of pottery in their new found location [as it is not noted whether these pottery had affinities with examples found in the aforementioned central Saharan region], at a time when it was trendy to carry stuff in pottery ware in the Saharan-Sahelian zone, with the filling up river systems due to the Monsoon rains.

The 10,000 and 9,000 BC (Phase 1 of the Holocene in Ounjougou): "The first sedimentary sequence of the Holocene can be observed at the Ravin de la Mouche. It's a channel dug into yellow Pleistocene silt and filled with coarse grained sand and pebbles. As a chronological reference for the upper levels of this early Holocene site, we hold ten radiocarbon dates between 9400 and 8400 BC cal. The associated lithic industry evidences predominantly a unidirectional mode of debitage. But also other technologies, such as bipolar on anvil or multidirectional, have been applied by the Early Holocene population. The raw material mainly used was quartz. The typological range consists of small retouched flakes, geometric microliths and perçoirs, but also of continuously retouched bifacial arrowheads and backed points." — Human population and paleoenvironment in West Africa [see: Link]

"By" 11,000 years BP ~ by 9050 BC:

"The age of the sediment in which they were found suggests that the six ceramic fragments discovered between 2002 and 2005 are at least 11,400 years old. Most ancient ceramics from the Middle East and the central and eastern Sahara regions are 10,000 and between 9-10,000 years old, respectively." — Human population and paleoenvironment in West Africa [see: Link]

By the 'beginning' of 8,000 BC: "Outstandingly, there has been evidence of the presence of pottery and seed grinding implements since at least the beginning of the 8th millennium BC. It is therefore the oldest site. The eighth millennium (Phase 2 of the Holocene in Ounjougou) known of this socio-economic type in sub-Saharan Africa...

The pottery and the seed grinding implements of phase 2 of Ounjougou are the oldest artefacts of this type known at present in sub-Saharan Africa. To current knowledge, the pottery of Ounjougou could either have been invented in the actual Sudano-Sahelian zone or been imported from the Central Sahara, where there has been evidence since the ninth millennium BC. Still, the oldest pottery known in the Sahara, from the site of Tagalagal in Niger, is already quite diversified at the moment of its appearance, possibly meaning that the technique has been introduced.

The lithic industry of the phases 1 and 2 on the other hand shows similarities to both more southern and Saharan industries. Quartz microliths, obtained through bipolar debitage on anvil, are a characteristic of the West African techno-complex according to Kevin MacDonald. Bifacially retouched arrowheads, in contrast, are specific for Saharan production." — Human population and paleoenvironment in West Africa [see: Link]

"The eighth millennium (Phase 2 of the Holocene in Ounjougou): The subsequent Holocene sequence is well documented by two principal sites, the Ravin du Hibou and Damatoumou. The archaeological levels can be quite clearly chronologically placed by means of a date obtained through OSL measurements (9420±410 Ka) and seven radiocarbon dates (between 8000 and 7000 BC cal). The lithic industry, exclusively quartz, is characterised by unidirectional, bidirectional and peripheral debitage, as well as by bipolar on anvil. There are essentially microlithic tools: perçoirs, backed points, notched pieces, denticulates, scrapers, retouched flakes and geometric microliths. Some small bifacially retouched arrowheads were also found on those sites. At the Ravin du Hibou, seven sherds have been found during excavation. They are heavily fragmented and thus preventing the reconstruction of the form of the vessel. Quartz has always been used as a temper. In just a single case, grog has been used in addition. Two shards show identifiable decorations. Two different techniques have been used: A rolled impression, possibly made with a peigne fileté souple or with a cordelette, and a simple comb impression. There were also seed grinding implements discovered at the Ravin du Hibou, a fragment of a seed grinding stone and a cylindrical upper grinding stone." — Human population and paleoenvironment in West Africa [see: Link]

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On the DNA side:

If we look at the samplings undertaken thus far, the west African populations on Atlantic-bordering west coasts—like the Senegalese samples, these groups undoubtedly have amongst the highest frequencies of E3a lineages, but there is something to be discerned: These groups largely carry M2, P1, and M180 lineages devoid of the M191 mutation, perhaps indicating the earlier E3a bearers, while many of the Bantu speaking groups of central, east and southern Africa carry those 191 derivatives:

Although haplotypes 22, 24, and 41 were probably all involved in the Bantu expansion, the processes that determined the current distribution of these haplotypes in the Sudanese belt (a region south of the Sahara extending from western to central Africa) seem to have been more complex and perhaps involved a separate expansion. In particular, haplotype 24 and its derivative, haplotype 22, harbor opposite clinal distributions in the region, a finding that is at odds with the hypothesis of a parallel dispersion of these two lineages in the area.

Haplotype 22 has a frequency of 23% in Cameroon (where it represents 42% of haplotypes carrying the DYS271 mutation), 13% in Burkina Faso (16% of haplotypes carrying the DYS271 mutation) and only 1% in Senegal (Semino et al. 2002), whereas haplotype 24 reaches its highest frequency (81%) in Senegal (Semino et al. 2002).

A possible explanation might be that haplotype 24 chromosomes were already present across the Sudanese belt when the M191 mutation, which defines haplotype 22, arose in central western Africa. Only then would a later demic expansion have brought haplotype 22 chromosomes from central western to western Africa, giving rise to the opposite clinal distributions of haplotypes 22 and 24. — Cruciani et al. 2002

The above suggests that the oldest E3a bearing population(s) ultimately moved to the far west corner of the continent.

From Semino et al. 2004, we have:

It is also of interest, that the Senegalese samples have higher E3* frequency, which attains its highest frequency in Ethiopian populations, than the Bantu speaking groups, where the only group tested positive, was that of the South African Bantu sample:

Bantu (South Africa) - E3* = 1.9%, Senegalese - E3* = 2.9%, Ethiopian (Amhara) - E3* = 10.4%, Ethiopian (Oromo) - E3* = 12.8% in the ascending order.

The Senegalese sample also bears the E-M.35* lineages:

In descending order…

Ethiopian (Oromo) - E-M35* = 19.2%, KhoiSan (South Africa) - E-M35* = 16.7%, Ethiopian (Amhara) - E-M35* = 10.4%, Berber (North-Central Morocco) - E-M35* = 7.9%, Berber (Southern Morocco) - E-M35* = 7.5%, Senegalese - E-M35* = 5%, Tunisian - E-M35* = 3.4%, Algerian - E-M35* = 3.1%, Arab (Morocco) - E-M35* = 2.3% , Burkina Faso -E-M35* = .9%

E-M78 in descending order….

Arab Morocco = 42.9%, Oromo = 35.9%, Amhara = 22.9%, Sudan =17.5%, Tunisian = 15.5%, Berber (Southern Morocco) = 12.5%, Arab (Morocco) = 11.4%, Berber (Morocco) = 10.9%, Algerian (32) = 6.3%, Berber (north central Morocco) = 1.6%, North Cameroon = 1.3%, Senegalese =.7%

E-M81 in descending order…

Saharawish (North Africa) = 75.9%, Berber (Morocco) = 68.7%, Berber (north central Morocco) = 65.1%, Berber (southern Morocco) = 65%, Algerian = 53.1%, Arab (Morocco) = 52.3%, Arab (Morocco) = 32.6%, Mali = 29.5%, Tunisian = 27.6%, Sudan = 5%, Senegalese = .7%

E-M33 in descending order…

Mali = 34.1%, North Cameroon = 7.9%, Senegalese = 5%, Burkina Faso = 3.8%, Saharawish (North Africa) = 3.4%, Berber (north‐central Morocco) = 3.2%, Sudan = 2.5%, Berber (Morocco) = 1.6%

E-M75 in descending order…

Bantu (South Africa) = 15.1%, Burkina Faso = 11.3%, Khoisan (South Africa) = 4.6%, Sudan = 5%, North Cameroon = 3.3%, Senegalese = 2.9%, Ethiopian (Oromo) = 1.3%

Looking at this data, among predominantly E3a-bearing Niger-Congo language speakers, Senegalese groups have the highest E3* frequency, as well as E-M35*. It follows the North Cameroon sample in this instance, in the E-M78 frequencies - though I’m not sure if those North Cameroon samples comprise of Niger-Congo speaking groups, Nilo-Saharan or some other language phylum group. In west Africa, it succeeds only Mali [and Niger, which wasn‘t included in this sample]—as one of the areas which have considerable Niger-Congo speakers—to have E-M81 bearing candidates, but then, Mali is also well known for its Saharan Tamazight speakers.

In reference to the above, some might look at a lineage as, say E-M78 and imagine it to be a trace of interaction with Saharan or coastal North African Afrasan speaking groups, but microsatellite inspection would indicate otherwise:

It is interesting that both E-P2* and E-M35* and their derivatives, E-M78 and E-M123, exhibit in Ethiopians the 12-repeat allele at the DYS392 microsatellite locus, an allele scarcely seen (Y-Chromosome STR Database), especially [b]in other haplogroups and other populations (A.S.S.-B., unpublished data). In addition, the Ethiopian DYS392-12 allele is usually associated with the unusually short DYS19-11 allele, which is typical of this area. These findings are not easily explained. One possible scenario is that an ancient differentiation of the E-P2 haplogroup occurred in loco (East Africa). However, this also implies a low mutability of the associated microsatellite motif (DYS392-12/DYS19-11). Alternatively, the microsatellite motif may be due to homoplasy.

The first scenario is more likely, since this unique microsatellite haplotype occurs in E-P2*, E-M35*, and E-M78 but is almost absent in all other haplogroups and populations. In addition, the high stability of the DYS392 locus (Brinkmann et al. 1998; Nebel et al. 2001) and of the shorter alleles of DYS19 (Carvalho-Silva et al. 1999) has been reported elsewhere. Moreover, the observation that the derivative E-M78 displays the DYS392-12/DYS19-11 haplotype suggests that it also arose in East Africa. This is illustrated by the microsatellite network (fig. 3, shaded area), which reveals that the Ethiopian branch harboring DYS392-12 is not shared with either Near Eastern or European populations.

The Ethiopian sample may not share the said allele with those populations mentioned, including the northwest African samples as far as I can tell, but it does share the said allele with the Senegalese sample, which would suggest that the Senegalese M78 derivative didn’t come from interaction with its northwest African neighbors; rather, they may well be relics of ancient migrations from east to west.

http://www.journals.uchicago.edu/na101/home/literatum/publisher/uchicago/journals/production/ajhg/2004/74/5/386295/images/medium/fg3.gif Source: Semino et al., Origin, Diffusion, and Differentiation of Y‐Chromosome Haplogroups E and J, 2004.

Some time during post 11ky ago expansions into the wet Sahara, before its return to aridity, with activity going on across the Saharan expanse, like cattle domestication for example, E3a bearers spread well into central-east Sahara. It was likely during this period that HbS mutations were localized, with the oldest E3a bearing groups nearer to the Atlantic-hugging west coasts bearing the Senegalese haplotype, while the Benin haplotype was able to have a more far-reaching expansion northward and northeast ward, due its situation in Niger River Valley vis-à-vis North Africa and the rest of the Sahara.
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Additional references to those mentioned in the body of the post:

*Semino et al., Origin, Diffusion, and Differentiation of Y‐Chromosome Haplogroups E and J, 2004.

* http://www.esd.ornl.gov/projects/qen/nercAFRICA.html

*Knight et al. 2003 : http://www.bec.ucla.edu/papers/Mountain_3-7-05.pdf

*Cruciani et al. 2004, Phylogeographic analysis of haplogroup E3b.

* Cruciani et al. 2007, Tracing Past Human Male Movements in Northern/Eastern Africa and Western Eurasia: New Clues from Y-chromosomal Haplogroups E-M78 and J-M12.