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Thread: Genetic signatures of gene flow & malaria-driven Nat-S in SSA of the "eBL belt"

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    Genetic signatures of gene flow & malaria-driven Nat-S in SSA of the "eBL belt"

    Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt"
    (Gouveia, 2019)







    Fig. 1 Populations studied in relation to major geographical barriers and analyses of population structure based on genotype data.


    Abstract:


    Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects populations with intense malaria exposure, in the so called “eBL belt” in sub-Saharan Africa. However, the effects of intense malaria exposure and sub-Saharan populations’ genetic histories remain poorly explored. To determine if historical migrations and intense malaria exposure have shaped the genetic composition of the eBL belt populations, we genotyped ~4.3 million SNPs in 1,708 individuals from Ghana and Northern Uganda, located on opposite sides of eBL belt and with ≥ 7 months/year of intense malaria exposure and published evidence of high incidence of BL. Among 35 Ghanaian tribes, we showed a predominantly West-Central African ancestry and genomic footprints of gene flow from Gambian and East African populations. In Uganda, the North West population showed a predominantly Nilotic ancestry, and the North Central population was a mixture of Nilotic and Southern Bantu ancestry, while the Southwest Ugandan population showed a predominant Southern Bantu ancestry. Our results support the hypothesis of diverse ancestral origins of the Ugandan, Kenyan and Tanzanian Great Lakes African populations, reflecting a confluence of Nilotic, Cushitic and Bantu migrations in the last 3000 years. Natural selection analyses suggest, for the first time, a strong positive selection signal in the ATP2B4 gene (rs10900588) in Northern Ugandan populations. These findings provide important baseline genomic data to facilitate disease association studies, including of eBL, in eBL belt populations.






     

    S6 Fig The proportions of individual ancestry values were calculated using ADMIXTURE unsupervised mode with the number of ancestral K = 2 to K = 15. (Bottom) ADMIXTURE cross-validation errors as a function of K.



     

    S7 Fig. Mean ancestry composition inferred by ADMIXTURE for Ghanaian and Ugandan populations in relation to 19 Pan-African populations.



     

    S11 Fig. Principal component analysis of the resampled PA non-LD dataset with similar number of individuals for each studied population.

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    What does it mean if I'm AG on rs10900588? Am I malaria resistant?

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    Nice to see that they used ethnolinguistic terms instead of geographic ones like they do in other studies.

    By the way, how come there are Ghanaian outliers in the PCA but not in the admixture analysis?

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    The Acholi and especially Langi (Luo Nilotic speakers) show significant Bantu ancestry, which should be expected. The Baganda don't show much Nilotic or Cushitic ancestry, and plot close to the Mbukushu from Botswana. The Burundians and Rwandans show higher levels of non-Bantu ancestry, even excluding the Tutsi-like outliers. The PCA shows the Tutsi-like Burundians pulling very slightly "upwards" relative to the Tutsi-like Rwandans, which fits with the higher Nilotic ancestry in Burundi than Rwanda noted by Tutsis testing privately.

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  7. #5
    Seems to be mostly Black Niger-Congos if im not wrong. How is the sickle-cell gene traits pass down, is it triggered by malaria in certain groups? is it universal, but prominent in some areas of the world?

    How resistant are Erythrean Northeast Africans in contrast to sickle-cell?
    Last edited by Muslim-Arbegna; 11-07-2019 at 06:08 AM.

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    double post
    Last edited by Megalophias; 11-17-2019 at 05:02 PM.

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    Quote Originally Posted by Muslim-Arbegna View Post
    Seems to be mostly Black Niger-Congos if im not wrong. How is the sickle-cell gene traits pass down, is it triggered by malaria in certain groups? is it universal, but prominent in some areas of the world?

    How resistant are Erythrean Northeast Africans in contrast to sickle-cell?
    Sickle cell trait is carried by a single genetic variant, which is inherited in the usual way. If you have one copy of this variant (inherited from one parent) it increases your resistance to falciparum malaria without much downside. If you have two copies you get sickle cell disease, which very bad - usually fatal without modern medical care.

    In areas with a high incidence of falciparum malaria the frequency of the sickle cell allele tends to rise to the point where the number of kids dying of sickle cell disease balances out the number surviving thanks to sickle cell trait. This can start out as only a very low frequency of sickle cell allele introduced by minor gene flow from some other population. Likewise, since sickle cell allele is harmful when falciparum malaria is not present, its frequency is expected to fall when a population carrying it moves into non-malarial areas. There are also many other genetic traits which increase malaria resistance, and often cause their own blood diseases, notably alpha and beta thalassemias - when these are already at high frequency they may interfere with the advantages of sickle cell trait. So while sickle cell is common in malaria-prone areas, including parts of India, Arabia, and southern Europe, it is not universal. I don't think it has a significant presence east of India.

    From what data I have seen sickle cell allele is rare or absent in the Horn of Africa, at least in the highlands - I don't know about Somalia. Malaria is still present in most of the region though. G6PD deficiency and some kinds of thalassemia seem to exist in Ethiopia, but I didn't find any specifics in the half-assed research I did. The Duffy negative variant, which confers resistance to vivax malaria, is apparently not too common in highland Ethiopia either despite being ubiquitous in tropical Africa (Khoisan don't have it either, but Nilotes do). Note that at high elevations in the Horn not only is malaria less frequent but there are red blood cell adaptations to high altitude, I don't know if malaria resistance traits could interfere with high altitude adapatation or not.

    Interesting topic, anyway.

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    Quote Originally Posted by Angoliga View Post
    Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt"
    (Gouveia, 2019)







    Fig. 1 Populations studied in relation to major geographical barriers and analyses of population structure based on genotype data.


    Abstract:









     

    S6 Fig The proportions of individual ancestry values were calculated using ADMIXTURE unsupervised mode with the number of ancestral K = 2 to K = 15. (Bottom) ADMIXTURE cross-validation errors as a function of K.



     

    S7 Fig. Mean ancestry composition inferred by ADMIXTURE for Ghanaian and Ugandan populations in relation to 19 Pan-African populations.



     

    S11 Fig. Principal component analysis of the resampled PA non-LD dataset with similar number of individuals for each studied population.
    i noticed that somalis have an additional component thats colored in aqua on the S7 Fig, is it representing additional nilotic ancestry?
    Last edited by afbarwaaqo; 11-21-2019 at 03:13 AM.

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    Quote Originally Posted by afbarwaaqo View Post
    i noticed that somalis have an additional component thats colored in aqua on the S7 Fig, is it representing additional nilotic ancestry?
    Sort of; the green component is maximized in Amhara, who have additional West Eurasian ancestry relative to Somalis, so Somalis need something else to represent their higher East African ancestry. But it doesn't have to be very closely related to Nilotes, and it doesn't have to have admixed into Somalis after the common ancestry of Amharas and Somalis.

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  14. #10
    Quote Originally Posted by Megalophias View Post
    Sort of; the green component is maximized in Amhara, who have additional West Eurasian ancestry relative to Somalis, so Somalis need something else to represent their higher East African ancestry. But it doesn't have to be very closely related to Nilotes, and it doesn't have to have admixed into Somalis after the common ancestry of Amharas and Somalis.
    What does the green component represent exactly? It seem to be accurate. Somalis have extra HG dna that is not found in proto-Cushitic people, "Habeshas" have it (Omotic) and it's detectable and minor, the Somali may have other non-Khoisan HG native to Somalia. Somalis lean closer to Boranas who have know to mixed with Non-Erythrean tropical Africans

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