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Post by djoser-xyyman on Sept 30, 2013 19:58:00 GMT -5
Since things are slow on AE I decided to do some research on African populations “off the coast of West Africa”. Namely, Azores, Canaries and ,…Cape Verde. They are of interest to me because I am trying to understand African migration off of the main land. There is a lot of work still to be done on Crete and Sardinia but I decided to spend some time on other islands off the other Africa coast. I remember reading one paper about a year ago that questioned the common belief that Cape Verde was NOT occupied when Europeans conquered it. It was “documented” that it was uninhabited. That paper seems to indicate that there were unique genetic composition found only on Cape Verde and NOT the West African mainland. Following up on that, I came across this 2013 paper that answered so many of my questions on skin pigmentation …in ways I did not imagine. I have been waiting for just such an extensive piece of work like this for years…since Kittles, Norton et al (2010).
This is not for the faint of heart – it can get very intimidating technical. But let’s walk through it.
For those who don’t know Shriver is the big dog on this one. He is Norton’s boss(mentor)…at least at one time. Point being they share similar approaches to skin pigmentation. BTW – Cape Verde is a large chain of islands off the coast of West Africa similarly to the Canaries being off the coast of North Africa. It (Canaries)was “claimed” by Europeans during colonial timers but it was first occupied by Africans about 3000BC….long before Europeans. The indigenous people carry male hg-E which we all know to be African. The same is true for Sardinia and Crete ie occupation by North Africans.
Genetic Architecture of Skin and Eye Color in an African- European Admixed Population – Mark Shriver (2013)
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Post by djoser-xyyman on Sept 30, 2013 19:59:28 GMT -5
First ...For those who learn through pictures  x  xx  |
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Post by djoser-xyyman on Sept 30, 2013 20:00:21 GMT -5
Genetic Architecture of Skin and Eye Color in an African- European Admixed Population – Mark Shriver (2013)
Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3610262, SLC24A5 P = 9.661029) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4610227, TYR P = 1.161029, APBA2[OCA2] P = 1.561028, SLC45A2 P=661029) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (,44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ,70% of the estimated heritability..
TRANSLATION – 4 GENES FOR SKIN COLOR AND 2 GENES FOR EYE COLOR. THERE ARE OTHER PIGMENTATION GENES BUT THESE SIX EXPLAIN ABOUT 35-70% OF THE DIFFERENT SKIN SHADES OF ADMIXED-AFRICANS IN CAPE VERDE
Blond or red hair color is very rare in Cape Verde, but there is a wide spectrum of variation in both eye and skin color, and individuals with dark skin and blue eyes are not infrequent.
TRANSLATION – BANTUS with BLUE EYES ARE NOT UNCOMMON.
Here we apply and compare genotype-based and ancestry-based association approaches for skin and eye color in 699 Cape Verdean individuals; both approaches identify two major loci for eye color, and four major loci for skin color. Surprisingly, the genetic component with the greatest effect on skin color is not a single locus but average genomic ancestry, which, together with these four major loci, accounts for most of the estimated heritable variation. Our results indicate that Cape Verdean pigmentary variation is the result of variation in a different set of genes from those determining variation within Europe, suggest that long-range regulatory effects help to explain the relationship between skin and eye color, and highlight the potential and the pitfalls of using allele distribution patterns and signatures of selection as indicators of phenotypic differences
The pattern of African genomic ancestry in Cape Verde is less skewed than in many other African-European populations. For example, in a randomly sampled African-American cohort from the Family Blood Pressure Study (FBPP) [21], African genomic ancestry ranges from 40.6% to 99.3%, with a ***median of 89.5% ***(Figure 1b).
TRANSLATION – THEY ARE QUESTIONING THE CORRELATION OF GENOMIC ANCESTRY vs SKIN COLOR IN AFRAMs..
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Post by djoser-xyyman on Sept 30, 2013 20:02:01 GMT -5
The strong effect of genomic ancestry on skin color is also striking in the context of eye color; there is only a weak correlation between skin and eye color in Cape Verdeans (R‘2 =0.14), and African genomic ancestry is also weakly correlated (R‘2 = 0.08) with eye color (Figure 1c, 1d). Overall, these observations point to different genetic architectures for skin and eye color.
TRANSLATION – THERE SEEM TO BE LITTLE CORRELATION BETWEEN SKIN COLOR AND EUROPEAN ANCESTRY IN EURO_AFRICANS ALSO.
For skin color, the most strongly associated SNPs at 5p13.3 and 15q21.1 represent missense alterations in two well-known pigmentary genes, SLC45A2 L374F (Figure 4a) and SLC24A5 A111T (Figure 4c), thought to encode membrane transport proteins that promote melanogenesis [13,25–27]. Neither amino acid substitution is predicted to dramatically alter protein function; nonetheless, expression of both genes is pigment cell-specific, and null mutations dramatically ***impair ***melanin synthesis in model organisms [13,28,29]. Thus, ***the European alleles probably represent hypomorphic alterations that compromise melanogenesis, leading to DECREASED pigmentation***.
However, GRM5 and APBA2 lie 396 kb upstream and 1025 kb upstream of TYR and OCA2, respectively, two well-known pigmentary genes for which a complete loss-of-function causes albinism in humans and in other animals [30–32].
Thus, the effects of HERC2 and APBA2 are genetically and statistically separable. Still, there is strong experimental evidence that the HERC2 region represents regulatory variation that acts via OCA2 [33], and therefore we refer to these loci as HERC2 (OCA2) and APBA2 (OCA2) to indicate both their proximity to a well-known pigmentation gene, and a likely molecular mechanism
The association of HERC2 and SLC24A5 with eye color is also apparent in individuals who do not have blue or green eyes: In the subset of 592 Cape Verdeans whose T-index .0.15 (Figure 1, Figure 2), both loci remain highly significant (HERC2 rs12913832, P = 5.23610216; and SLC24A5 rs2470102, P = 1.12610210), indicating that variation at these loci affects different shades of brown eye color.
Notably absent from the four skin color loci detected in this study are ASIP and KITLG, reported previously to affect skin color in populations with African-European admixture [12,15], and IRF4, MC1R, SLC24A4, TYRP1, reported previously to affect skin color in populations of European ancestry [4,6].
To explore these ideas, we first examined worldwide allele frequency distributions for the most strongly associated SNP at each locus, using information from the Human Genome Diversity Project (HGDP) [39] and HapMap III [19]. THE DERIVED APBA2 (OCA2) ALLELE IS PRESENT AT LOW FREQUENCIES IN ***MOST POPULATIONS*** OF AFRICAN ANCESTRY, AND AT HIGH FREQUENCIES IN MOST POPULATIONS OF ASIAN AND EUROPEAN ANCESTRY. By contrast, the derived HERC2 (OCA2) allele is absent??? from African and East Asian populations, and appears at high frequency only in Western and Northern Europe (Figure 6a, 6b). These results suggest that an APBA2 (OCA2) mutation conferring light skin arose BEFORE the spread of humans out of Africa, and that a HERC2 (OCA2) mutation conferring pale eye color arose much later.
SELF EXPLANATORY. TRANSLATION – AFRICANS CARRIED THE GENE FOR LIGHT SKIN BEFORE EUROPEAN INVADED. THERE WERE LIGHT SKIN AFRICANS BEFORE WHITE EUROPEANS EVER EXISTED.
HERE IS YOUR BREAD CRUMS.. MIKE!!!.
OHH! AND KEEP MIND IT HAS BEEN CITED THAT THE LUYHA(GREAT LAKES) CARRY HERC2 AND ALSO HAVE THE BLUE EYES PHENOTYPE ALBEIT AT LOW FREQUENCY. NOTICE, ON BLUE EYES, THE AUTHOR SAID MUCH LATER AND NOT –NOT- IN AFRICA.
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Post by djoser-xyyman on Sept 30, 2013 20:02:42 GMT -5
extended haplotypes for the derived alleles are separated by ,800 kb, and approximately half of the European chromosomes we examined carry an ancestral HERC2 (OCA2) haplotype together with a derivative APBA2 (OCA2) haplotype, or vice versa (Figure 6c). These observations are consistent with the presence of discrete CMS peaks under the HERC2 (OCA2) and APBA2 (OCA2) regions (Figure 4d) and suggest that the loci may have undergone selection independently in European populations.
TRANSLATION – LIGHT SKIN AND LIGHT EYES DO NOT NECESSARILY CORRELATE.
The four skin color loci we identified by association analysis act in an ADDITIVE fashion: ]we found no evidence of dominance at any of the loci, nor evidence of opposite-sign epistasis between loci. For eye color, the ancestral HERC2 (OCA2) allele is mostly dominant over the derived allele, consistent with the near recessive mode of inheritance of blue eye phenotype in Europeans (Figure S3). By contrast, the effects of SLC24A5 on eye color are semi-dominant, and no interaction was found between this gene and HERC2.
TRANSLATION – THERE IS NO SINGLE LIGHT/WHITE GENE. THE FOUR SKIN PIGMENETATION GENE IDENTIFIED HERE ARE CUMULATIVE. ..MEANING THE MORE YOU HAVE THE LIGHTER YOU ARE. HOWEVER LIGHT EYES (GENES) BEHAVE DIFERENTLY. PRESENCE OF SLC24A5 along with HERC2 is VERY IMPORTANT. BOTH SETS OF LOCI ARE INDEPENDENT. THEY ARE SPECULATING ON SEXUAL PREFERENCE THING. TO ME IT DOES NOT MAKE BIOLOGICAL SENSE. NOTICE NO MENTION OF THE JABLONSKI FOOD NONSENSE. BUT LET US CONTINUE.
These quantitative genetic relationships and their contributions to skin color variation in Cape Verde are depicted in Figure 6 as overlapping regions; the four major loci contribute a total of 35% to skin color variation, but only 13% above that which could also be accounted for by individual ancestry. . Conversely, even though individual ancestry contributes 44% to skin color variation, about half of that contribution (22% of the total) could also be accounted for by genotype at the four major loci. The aforementioned discussion considers the different components as a proportion of total variation, NOT ALL OF WHICH IS HERITABLE. Previous studies of skin color estimate narrow sense heritability at 70%–90% of total variation [40], and genotype of the four major loci together with individual ancestry accounts for 57.
TRANSLATION – LIGHT SKIN IS **NOT** INDICATIVE OF EUROPEAN ADMIXTURE. THERE WERE “WHITE” INDIGENOUS AFRICANS. SERGI COMES TO MIND ON HIS STATEMENT ABOUT THE PEOPLE OF THE ATLAS MOUNTAINS. “AFRICAN IN EVERY WAY EXCEPT FOR THE SKIN AND EYES.”. RELETHORD ET AL ALSO COMES TO MIND. THE MOST DIVERSE SET OF SKIN PIGMENTATION IS FOUND IN SUB_SAHARAN AFRICA.
Discussion
Previous genome-wide studies of human skin and eye color have focused on populations of European ancestry and have been based primarily on categorical and subjective assessment of pigmentary phenotype [4–7].
TRANSLATION – MANY PREVIOUS WORK IS BIAS IN FAVOR OF EUROPEANS…FOR OBVIOUS REASON?
OCA2 was originally considered a strong candidate gene for Afro-European pigmentary variation based on allele distribution patterns of closely linked SNPs [11,14,34,35], and because of a strong association with blue vs. brown eye color in populations of European ancestry [4,41]. This eye color locus was later refined to a small region 50 kb upstream of OCA2 in an intron of the HERC2 gene [7,8,10]. Very recently, Visser et al. [33] showed that the critical SNP in this region, rs12913832, is part of an enhancer that forms a chromatin loop with the OCA2 promoter, and that the derivative allele causes reduced recruitment of the chromatin remodeler HLTF, leading to reduced binding of additional transcription factors and impairment of loop formation and OCA2 expression in cultured human melanocytes.
MIKE THIS IS YOURE CUE!!!
Neither functional nor expression studies suggest a role for the APBA2 protein in pigmentation [42–44]; instead, we favor the hypothesis that the action of ABPA2 (OCA2) is analogous to that of HERC2 (OCA2), with distinct cis-acting regulatory regions that can affect eye and skin color independently. Critical evaluation of this hypothesis will require functional studies similar to those …
In particular, loss-of-function for OCA2 can cause blindness due to loss of melanin from retinal pigment epithelial cells [31], and we speculate that natural selection for the APBA2 region in Europeans represents cell typespecific regulation that promotes fair skin while preserving visual function. Finally, our population genetic analysis of HERC2 and APBA2,
For SLC24A5, this apparent discrepancy stems from whether effect sizes are described as a fraction of the ‘‘average pigmentation difference between European-Americans and African Americans of about 30 melanin units’’ [13], or the entire dynamic range within a population, which is 77 melanin units in Cape Verde. Indeed, we estimate an
KITLG remains a good candidate gene; however, any effect in the Cape Verde population is too small to be detected in our sample. for potential forensic applications, and argue that efforts to predict pigmentary phenotype from genotype should be based on dense genotype and/or whole genome sequence information rather than small panels of SNPs. ONE SHOULD NOT CHOOSE ONE GENE and LABEL IT A PIGMENETATION GENE. THERE IS NO SUCH THINK AS “A” PIGMENTATION GENE. NORTON, KITLLEs ET AL COMES TO MIND.
My SUMMARY
In short West Africans carry genes for light skin(Nigerian Couple with the white baby comes to mind-when the stars align…bingo).. However other researchers have detected HERC2 and SLC24A5 in Central Africans albeit at low frequency(resulting in blue eyes). Bottom-line these researchers are saying there were “white” Africans before white Europeans ever existed.
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Post by djoser-xyyman on Sept 30, 2013 20:23:42 GMT -5
To be clear the author confirms that Africans carried the genes for light skin PRIOR to leaving Africa.
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Post by azrur on Oct 7, 2013 21:57:55 GMT -5
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Post by djoser-xyyman on Oct 25, 2013 5:05:46 GMT -5
Quote:
To explore these ideas, we first examined worldwide allele frequency distributions for the most strongly associated SNP at each locus, using information from the Human Genome Diversity Project (HGDP) [39] and HapMap III [19]. THE DERIVED APBA2 (OCA2) ALLELE IS PRESENT AT LOW FREQUENCIES IN ***MOST POPULATIONS*** OF AFRICAN ANCESTRY, AND AT HIGH FREQUENCIES IN MOST POPULATIONS OF ASIAN AND EUROPEAN ANCESTRY. By contrast, the derived HERC2 (OCA2) allele is absent??? from African and East Asian populations, and appears at high frequency only in Western and Northern Europe (Figure 6a, 6b). These results suggest that an APBA2 (OCA2) mutation conferring light skin arose BEFORE the spread of humans out of Africa, and that a HERC2 (OCA2) mutation conferring pale eye color arose much later.
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Post by herodotus on Oct 25, 2013 7:32:54 GMT -5
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Post by herodotus on Oct 25, 2013 7:43:44 GMT -5
In the next decade they will probably discover the non-pigmentation phenotype effect of Ala111Thr in South Indians. This will also explain it in an African context. It doesn't mean Africans were "white" anymore than South Indians.
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Post by djoser-xyyman on Oct 25, 2013 8:24:13 GMT -5
Shriver 2013....not 2007, 2005. Quote: 1. mutation conferring light skin arose ***BEFORE***** the spread of humans out of Africa. 2. something else is going .....yeah...CUMULATIVE!!!!! 3. OP "white?" there is a reason behind that. It is important to read and keep up to date. |
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Post by herodotus on Oct 25, 2013 13:54:39 GMT -5
You interchanged "light" with "white" which is misleading. Ala111Thr (SLC24A5) is associated with white skin in Europeans. KITLG and APBA2 (OCA2) however is associated with light brown or tawny shades. The depigmentation in Europe was not sudden but an ongoing process that went through at least two phases, from light brown > tawny > white. Dates here are still disputed but Beleze et al. 2012 concludes the final depigmentation phase occurred through increase in population size towards the end of the Pleistocene: mbe.oxfordjournals.org/content/early/2012/08/27/molbev.mss207My other point was that even if Africans carry Ala111Thr, this may have other affects on phenotype. Geneticists are now exploring such pleiotropism. Shriver et al. (2013) who assert "APBA2 (OCA2) mutation conferring light skin arose before the spread of humans out of Africa" don't take this into account. Anyway, APBA2 (OCA2) is not associated with whiteness, but like KITLG, skin lightening. Shriver et al. (2013) say nothing about "white Africans". |
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Post by djoser-xyyman on Oct 26, 2013 6:39:22 GMT -5
sigh! don't get. cumulative and Semantics
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Post by djoser-xyyman on Nov 6, 2013 22:19:13 GMT -5
Let me explain the study on “white West Africans” to the newbies and lurkers.
This is probably one of the most up-to-date study on human skin pigmentation since the famous Kittles, Norton Study of 2010. I stumbled across this by accident. It is ground breaking but I am not sure why it isn’t getting the deserved play.
Reputable researchers have moved beyond SLC45A2 as a “white” or European gene. Rees et al and Mekova et al etc think that the vit D hypothesis is nonsense. I agree.
Cape Verde is apparently ideal for this study. Better than Aframs. Apparently they are more admixed than Aframs.
What the researchers are trying to do is correlate skin shade with gene frequency at four Loci. SLC45A2 is just ONE of the FOUR loci for skin pigmentation in this study. Remember Kittles and Co. speculated on about six. Other researchers speculated that there are about 10. East Asians are light skin and yet they do NOT carry a high frequency of SLC45A2. In fact many East Asians are lighter than Europeans. See the world pigmentation chart. Or walk the streets of LA or Philly Chinatown(eyeballing LOL!), you will see. Hence the title of the famous Kittles and Norton paper.
Getting back to the “White West Africans”(Notice the West Africans carry 25% **derived** SLC45A2 – Sub-Saharans are NOT 25% admixed with Europeans). See study. He! He! He! -
Authors concluded several things.
1. There are FOUR skin pigmentation gene not ONE. The four genes are ADDITIVE!!! That means the more you have of the four genes the lighter is that population/person.
2. They concluded that there is NOT a direct correlation between so called “European” admixture and light skin in Cape Verdeans. Hence “unexplained heritability”. This what one of the charts I posted shows. They used mathematical models to come to that conclusion.
3. They included other primates in the study, which is sound science, to determine the ancestral (underived) genotype. Concluding that the genes origin is IN Africa. Thus their conclusion “light skin originated” BEFORE AMH left Africa.
4. They made no such statement about blue eyes. No data to prove it. …to be continued.
5. They also speculated that Mike is right. Europeans ARE Albinos. But not as simplistic as Mike puts it. I knew this over a year now. But they are NOT Dravidian Albinos either. The geneticists suggested that pigmentation ALWAYS goes back to the OCA2(Albino) gene, In other words the other genes are a “red-herring”. They suggested that it is due to LD that many OTHER researchers zero in on genes. Such as SLC45A2, ASIP etc. That means the “close proximity”(LD) of OCA2 can mis-lead researchers.
6. It doesn’t matter what YOU, Sage, racialists, what you see on TV or Google images, religious belief, or modern politicians think. This is what the data shows. You cannot dispute the facts or data. Word games like “associated”, affinity etc does nothing to me. I am a vet. You may get a knee-jerk reaction from newbies when you use those words. I am debating ORIGIN.
No gene or phenotype originated IN Europe. Europe is a geographic and genomic extension of Africa.
There…. I broke it down for you. If I have to spell this out for you then we should not be having this discussion. And how can we then discuss blue eyes, HERC1 and HERC2.
I hope you understand this statement - ”(Notice the West Africans carry 25% **derived** SLC45A2 – SSA are NOT 25% admixed with Europeans). See study. He! He! He! - Now you can see WHY Relethord et al made that statement.
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Post by herodotus on Nov 6, 2013 23:40:26 GMT -5
You're posting lots of disinformation. Derived SLC45A2 (rs16891982) is absent in Sub-Saharan Africans. It only appears in northern coastal populations through recent gene flow with Europeans:  Where is this 25% in West Africa you speak of?  rs16891982 is also not the major allele responsible for European skin lightening. You're confusing SLC45A2 with SLC24A5. The former is more linked to hair colour depigmentation (brown or blonde as opposed to black hair): J Hum Genet. 2008;53(11-12):966-71. doi: 10.1007/s10038-008-0338-3. Association of the SLC45A2 gene with physiological human hair colour variation. SLC24A5's derived Ala111Thr allele (rs1426654), not SLC25A2, has been shown to be the major factor in European skin whitening. SLC24A5 only entered Africans through recent gene flow, again, it predominates in northern coastals: "The non-African component, which includes the SLC24A5 allele associated with light skin pigmentation in Europeans, may represent gene flow into Africa, which we estimate to have occurred ∼3 thousand years ago (kya)." (Pagini et al. 2012) But yes, it also appears at low frequency in Sub-Saharan Africans (unlike SLC24A2). However if you are discussing ORIGIN, derived SLC24A5 and SLC25A2 are non-African, and European. They entered Africans through gene flow. There seems to be little evidence of purifying selection (for example South Indians carry SLC24A5 at a high frequency, yet they are dark brown skinned), so this is why as I already discussed pleiotropy. Conclusion: You don't know what you are posting. A "vet" in what? You can't even understand the data and are misreading tables. |
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