Study finds new genes that affect hair, eye and skin colour.

deCODE Discovers Genetic Variants Influencing Skin, Eye and Hair Colour 

Scientists at deCODE genetics and colleagues in Iceland and Holland have reported the discovery of variations in the human genome that influence pigmentation of hair, eyes and skin.  By studying more than 300,000 SNPs (single-letter variants in the human genome) across the whole genome in close to seven thousand individuals of European origin, the deCODE team discovered several novel SNPs influencing hair, eye, and skin pigmentation, at the same time refining earlier findings influencing these traits.
The findings help in the understanding of the molecular basis for and evolution of these most visible of characteristics, and may be useful for teasing out the biology of skin and eye disease as well as for forensic DNA analysis. The paper, entitled “Genetic determinants of hair, eye and skin pigmentation in Europeans,” has been published online in Nature Genetics.

It is known that pigmentation characteristics such as freckles and hair and eye colour run in families. However, only few genes have been strongly linked to normal variation of these characteristics. Skin pigmentation in human populations tends to be darkest near the equator and to lighten with increasing latitude. This variation has a generally accepted dual biological function: heavier pigmentation affords protection against ultraviolet radiation in sunlight, protecting against sunburn and skin cancer but also reduces the body’s capacity to synthesize vitamin D. By contrast, there is no clear functional role for hair and eye color. The vast majority of variations in these two traits is confined to populations of European origin, with most populations around the globe with only dark hair and brown eyes.

Most of the novel variants presented in this study demonstrate signs of positive evolutionary selection in people of European origin, and those contributing to lighter pigmentation of the skin appear to have been under the strongest selective pressure. Intriguingly, some variants contribute to variation in just one trait; others to two or three. Among the findings of the deCODE group is a SNP on chromosome 14 in the SLC24A4 gene that is associated with increased likelihood of blond as opposed to brown hair and blue as opposed to green eyes. A SNP on chromosome 6p25 is associated with an increased likelihood of freckles and skin sensitivity to sunlight, as well as to brown hair. A sequence variant near the KITLG gene on chromosome 12 is associated with an increased likelihood of having blond rather than brown hair. One SNP in the tyrosinase gene is associated with freckling, and another associates with the likelihood of having blue as opposed to green eyes, as well as to skin sensitivity to sunlight.

The deCODE team has also provided detailed support for the previously reported association in the MC1R gene with red hair, freckling and skin sensitivity to sun. Similarly, the well known association of variants near the OCA2 gene with eye and hair colour, was replicated but also substantially refined. Taken together, the variants described in this report enable prediction of pigmentation traits based upon an individual’s DNA.

According to deCode, this study has significantly improved the accuracy of predicting green eyes (SLC24A4, TYR), hair shade (SLC24A4, TYR, KITLG) and freckling (TYR, 6p25). Some of the novel association patterns differ in unexpected ways from previous findings. The variant in SLC24A4 is important for gauging likelihood of blue versus green eyes, but, in contrast to variants in OCA2, has only marginal impact on likelihood of blue versus brown eyes. The completely novel SNP discovered on 6p25 associates with freckles and brown hair, whereas the SNPs in MC1R associate with freckles and red hair. The multitude of genes affecting pigmentation and their varied effects are reflected in the great degree of diversity of pigmentation seen in Europeans.

A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation

 

 We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p=6.0×10−62 and p=7.46×10−127, respectively. The IRF4 SNP was also associated with skin color (p=6.2×10−14), eye color (p=6.1×10−13), and skin tanning response to sunlight (p=3.9×10−89). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p=0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

The genetics of hair, skin and eye colour are very intertwined, and I won’t even pretend to understand the intricacies of of it.

Paleolithic Europe populated from Asia

First Europeans Came From Asia, Not Africa, Tooth Study Suggests
Kate Ravilious
for National Geographic News
August 6, 2007
Europe’s first early human colonizers were from Asia, not Africa, a new analysis of more than 5,000 ancient teeth suggests.
Researchers had traditionally assumed that Europe was settled in waves starting around two million years ago, as our ancient ancestors—collectively known as hominids—came over from Africa.
But the shapes of teeth from a number of hominid species suggest that arrivals from Asia played a greater role in colonizing Europe than hominids direct from Africa.
These Asian hominids may have originally come from Africa, the scientists note, but had evolved independently for some time.
“Asia was also an important center for hominid speciation,” said Maria Martinón-Torres, a scientist at the National Research Center on Human Evolution in Burgos, Spain, who led the study.
The finding suggests that the hominid family tree could be much more complex than previously thought (explore an interactive atlas of human migration).
Species from the genus Australopithecus and the genus Homo arrived in Europe between two million and 300,000 years ago.
Until recently, a lack of fossils from this time period had made it difficult to piece together hominid evolution and migration patterns.
But using the latest fossil findings, Martinón-Torres and colleagues were able to examine more than 5,000 teeth from two-million-year-old Australopithecus and Homo skeletons from Africa, Asia, and Europe.
The shape of the teeth offered clues about each species’ genetic lineages.
“Teeth are like the safe-box of the genetic code,” Martinón-Torres said.
That’s because—compared to bones—teeth change shape very little once they are formed, and their shape is strongly influenced by genetics.
The researchers classified each of the teeth using more than 50 indicators, such as fissure patterns, overall size, and length-to-width ratio.
“We looked at the entire landscape of the teeth—the mountains, valleys, ridges—everything,” Martinón-Torres said.
What they found is that European teeth were more similar to Asian teeth than they were to African teeth.
However, the results don’t rule out African influence on European genes.
“This finding does not necessarily imply that there was not genetic flow between continents,” Martinón-Torres and colleagues write in their paper, “but emphasizes that this interchange could have been both ways.”
The work will be published in tomorrow’s issue of the Proceedings of the National Academy of Sciences.
Fluid Migrations
Rather than a one-way stream of people coming from Africa, Martinón-Torres and colleagues think there must have been a more fluid pattern of migrations.
“Just because people had come out of Africa didn’t mean that they couldn’t turn around and go back again,” she said.
The researcher also believes that climate, food, and geography were major influences on hominid migration patterns.
The Sahara, for example, presented a big barrier for movement out of Africa and directly into Europe (see photos and read a related feature about athletes who ran across the Sahara earlier this year).
Rather than struggling across the Sahara, it appears that human ancestors spread in many directions before arriving in Europe.
Erika Hagelberg, a geneticist from the University of Oslo in Norway, is impressed with the study, but cautious about how it should be interpreted.
“The study shows that the genetic impact of Asia on Europe is stronger than that of Africa. But the teeth can’t tell us the direction or the time when people migrated,” she said.
Nonetheless, the new study does complement direct gene studies and supports the idea that hominids evolved independently in many different parts of the world.
“The fossil teeth are a way to study the traits of past peoples,” Hagelberg said, “and help balance the work being done on the genes of people alive today.”

Well, duh, we knew that from the fossils. Nice to have corroborating evidence though.

Inhabited for 17,000 years. Franchthi cave, Greece.

A cut-and-paste for-the-record, frankenblog entry.

Franchthi Cave is on the very Southern part of Greece, easily accessible from Anatolia (sea levels were a lot lower about 11,000 years ago). From another source, I’ve found out the lentil seeds found at Franchthi are slightly larger than the wild kind, indicating an early stage of domestication. One of the Y chromosome studies I have on file suggests that an early population movement from Turkey to Greece, and I think that this place is a good possible site for their arrival. The caves suddenly gain four of the Neolithic founder crops simultaneously, and I think this is a giveaway for some kind of major cultural change.

Franchthi Cave is located in south eastern Argolid, across a small bay from the modern Greek village of Koilada. It is by far the longest recorded continuous occupational sequence from any one site in Greece. It is unique for having unbroken series of deposits spanning the period from ca. 20,000 B.C. down to ca. 3000 B.C. Excavation at the site began in 1967 and ended in 1976. The dates for the various phases of occupation in the cave are from radiocarbon analysis of a total of over fifty samples, the largest number of radiocarbon samples from any prehistoric site in Greece. The earliest radiocarbon date is ca. 20,000 B.C. for the Upper Paleolithic, the latest near 3000 B.C. for the Final Neolithic.

In the Paleolithic Period (ca. 20,000 � 8300 B.C.) inhabitants of the cave were probably seasonal hunter-gatherers. There is no definite evidence of plant gathering before ca. 11,000 B.C., although large numbers of seeds of the Boraginaceae family were found which may have come from plants gathered to furnish soft “bedding” or for dye, which their roots may have supplied. First appearing at ca. 11,000 B.C. are lentils, vetch, pistachios and almonds. Then ca. 10,500 B.C. and still well within the Upper Paleolithic Period appear a few very rare seeds of wild oats and wild barley. Neither becomes common until ca. 7000 B.C.At this time there is no evidence for habitation of the cave during the winter. The typical tool of this time is the backed bladelet, a tiny multi-purpose-cutting tool, but small end-scrapers (for removing the flesh from hides) are also common. There is no pottery or architecture at this time and also no burials have been found.

In the Mesolithic Period: (ca. 8300 � 6000 B.C.) the plant remains are much the same as in the preceding Paleolithic Period, with the exceptions that wild pears and a few peas begin to appear ca. 7300 B.C. and that wild oats and barley become common after 7000 B.C. The disappearance of the equid and caprine bones from the faunal assemblage, as well as an increase in the number of pistachios, all taking place ca. 8000 B.C. suggest a change of environment to open forests. There is also the possibility, however, that the change in the animal bones represents a change in the hunting preferences or practices of the cave�s inhabitants.

The second phase of the Mesolithic is characterized by the appearance of large quantities of large fish bones and the appearance of substantially larger quantities of obsidian from Melos as a material in the local chipped stone industry. These two developments imply that deep-sea fishing may have been done for the first time. Small, geometrically shaped tools (microliths) now characterize the chipped stone industry. There is still no pottery or architecture.

The earliest burial found at Franchthi is of a Lower Mesolithic date: a 25-year-old male was buried in a contracted position in a shallow pit near the mouth of the cave. The pit was covered with fist-sized stones but there were no burial goods. Further examination in 1989 of the human bone found throughout the cave resulted in the realization that there were five other burials throughout the cave. The bones were of different age groups, which leads to the conclusion that the inhabitants of the cave lived there on a permanent basis.

The beginning of the Neolithic Period (6000 � 5000 B.C.) at Franchthi Cave is characterized by the appearance of domesticated forms of sheep and goat, and the appearance of domesticated forms of wheat, barley and lentil. Also there was the appearance of polished stone tools and a significant increase in the number of grinding stones (for grinding grain) and sickle elements along with other edges used for cutting plants. Pottery had finally appeared in this era. The pottery of this time was dark and monochrome and mostly consisted of hole-mouthed jars and deep bowls. Judging by the size and shape of the pottery it was not used for cooking or storage but rather for display.

During this time, occupation began outside of the cave which brought the first signs of architecture, a sort of retaining wall. Blades seem to be more popular and fishhooks appear for the first time. An infant was also found buried with a clay vase, which may signify some sort of status system.

The wild oats, barley, lentils, pears and peas disappear; emmer wheat and cultivated or domesticated forms of barley and lentil occur for the first time. It is unknown whether the new plant forms were brought from elsewhere or developed locally from wild forms.

The Middle Neolithic (ca. 5000 � 4500 B.C.) is distinguished from the proceeding period by minor changes in the pottery. Potters had learned to purify their clay more thoroughly and to fire their products at higher temperatures and in larger batches, which required the stacking of vessels during the firing process with more carefully controlled conditions. There was also the use of a finer more lustrous, reddish slip or wash on the pottery. Patterns also became more linear although, 50% to 65% of the total pottery of this time still remained solid colored. For the first time, truly coarse clay pastes were used to produce pots fired at lower temperatures than the finer wares and having less carefully finished surfaces. These “course wares” seemed to function as cookware.

The Late Neolithic Period (4500 � 400 B.C.) is also distinguished by its changes in pottery. The pottery of this period is dull when compared to the lustrous paint of the previous period. The dullness is from the manganese-based paint, which has no luster and also does not vary in color when fired whereas the iron-based paints used in the previous period did. A new class of pottery appears referred to as Fine Black-burnished Ware, which was often decorated with fugitive white paint which usually survives only as a “ghost” or “negative” on the black-burnished surface.

In the chipped stone, barbed or barbed-and-tanged arrowheads appear, but are also seen as late as the beginning of the Early Bronze Age.

The last period at Franchthi Cave is the Final Neolithic (ca. 4000 � 3000 B.C.) and is viewed by many scholars as no more than a later stage of the Late Neolithic. The pottery of this period is a variety of odd handle types and a preference for plastic, as opposed to painted, decoration. Small amounts of odd wares for example, red-on-white painted, crusted, dark slipped-and-burnished and pattern-burnished also occur during this period.

In chipped stone, large triangular arrowheads of flint, bifacially flaked, are characteristic. Obsidian now accounts for 95% of the chipped stone at Franchthi. For the first time at Franchthi, the buried population of this time consists both of adults and children and both female and male. In the earlier periods the adult burials appeared to be secondary while the child burials were primary.

A few odd bits of Bronze Age material suggest that the cave had been visited sporadically over the next two millennia. Finds of specialized votive material at the back of the cave show that it served some sort of cult purpose in Classical times, but never was of residence to anyone after that. Franchthi Cave was abandoned around 3000 B.C. because of the steady rise in sea level. The broad terrace below the cave on which both the settlement and the harvest fields of the Neolithic inhabitants existed are now buried.

There are some terracotta figurines found in Franchthi cave, some dating back to the early Neolithic. For a good page with lots of artifacts from Franchthi including stone tools, go to this page, I have shamelssly stolen photos from it.

Burials at Franchthi

Burials of a unknown individual. Burial of an infant, buried with half a clay vase and a marble dish.

 Burials of a middle aged woman and a 25 year old male.

Possible evidence for Mesolithic agriculture in Europe.

Mesolithic agriculture in Switzerland? A critical review of the evidence.

February 2007.  

Abstract
Accumulating palaeobotanical evidence points to agricultural activity in Central Europe well before the onset of the Neolithic, commonly dated at ca 5500–5200 cal BC. We reinvestigated an existing pollen profile from Soppensee with refined taxonomical resolution by further subdividing the Cerealia pollen type into Triticum t. and Avena t. because the sediments at this site currently provide the highest temporal resolution and precision for the period of interest among all sites in Switzerland. Our new results are in agreement with previous high-resolution investigations from Switzerland showing scattered but consistent presence of pollen of Cerealia, Plantago lanceolata, and other cultural plants or weeds during the late Mesolithic period (6700–5500 cal BC). Chronologically, this palynological evidence for sporadic agricultural activities coincides with a major break in material culture at ca 6700 cal BC (i.e. the transition from early to late Mesolithic). Here, we review possible arguments against palaeobotanical evidences of Mesolithic agriculture (e.g. chronological uncertainties, misidentification, contamination, long-distance transport) and conclude that none of these can explain the consistent pollen pattern observed at several sites. The palynological evidence can, of course, not prove the existence of pre-ceramic agriculture in Central Europe. However, it is so coherent that this topic should be addressed by systematic archaeobotanical analyses in future archaeological studies. If our interpretation should turn out to be true, our conclusions would have fundamental implications for the Neolithic history of Europe. Currently, it is intensely debated whether Central European agriculture developed locally under the influence of incoming ideas from areas where Neolithic farming had already developed earlier (e.g. southeastern Europe) or whether it was introduced by immigrating farmers. On the basis of our results, we suggest that agriculture developed locally throughout the late Mesolithic and Neolithic. Mesolithic trading networks connecting Southern and Central Europe also support the hypothesis of a slow and gradual change towards sessile agriculture, probably as a result of incoming ideas and regional cultural transformation.

Unfortunately I can’t reproduce the whole article here. But I have the conclusion..

Indications of agricultural activity during almost the entire late Mesolithic are recorded in many pollen profiles. It seems highly unlikely that the palynological evidence of cultivated plants and adventive weeds could have originated from sources other than Mesolithic agriculture in the region, though we cannot completely exclude this reservation. The archaeological evidence is still less clear. The few credible radiocarbon dates suggest a chronological framework for the late Mesolithic between 6700 and 5500 cal BC, and the beginning of the proper Neolithic (i.e. agriculture,livestock, pottery and stone axes) around the middle of the sixth millennium BC. There is no credible evidence of bones from domesticated animals (with exception of dogs) from late Mesolithic assemblages, whereas in the early Neolithic goat and sheep (imported animals) played animportant role.

Considering the general palaeovegetational patterns and their chronology, we postulate a connection between the occurrence of the earliest cereal and weed pollen and thes triking cultural change at the transition from the early tot he late Mesolithic.

Equivalent developments can be observed in large parts of Europe. Agricultural adoption by indigenous hunter-gatherers as opposed to the partial or wholesale immigration of agriculturalists is a complex issue. Our combined palaeobotanical and archaeological evidences are in favour of the hypothesis of a gradual change, probably owing to incoming ideas and regional cultural transformation. In the Near East and in southern Europe (Greece, Italy), a pre-ceramic (or aceramic) Neolithic had developed before the onset of pottery-based agriculture. This innovation (cultivation of cereals without ceramic production) reached continental Greece at about the end of the eighth millennium BC and southern Italy at ca 7000 cal BC

Our systematic finds of pollen of cereals and weeds are younger than these dates (first clusters around 6600–6500 cal BC, although one single Triticum pollen grain occurred at ca 7800 cal BC at Soppensee).However, if they represent agricultural activities, such a rapid spread of agriculture across the European continent (reaching almost simultaneously Bavaria in the east and France in the west) could be explained by dynamic Mesolithic (exchange) networks transporting the idea of agriculture. Moreover, the material culture of the Central European late Mesolithic probably developed autochthonously, but with strong influences from the Mediterranean region. Given the striking change in material culture at 6700 cal BC we cannot, however, reject the hypothesis of an immigration of people from southern Europe that may have influenced local Mesolithic groups. Similarly, combined palaeobotanical and archaeological data (gradual increase of pollen indicative of agricultural activity over centuries, high continuity in silex culture) suggest that the proper Neolithic at ca 5500 cal BC developed autochthounously and that immigration of people as suggested for the loess areas of Central Europe was of minor relevance, which is corroborated by recent genetic results.

 Nonetheless, considering the disagreement with other palaeogenetic studies, more localised genetic samples are needed tothoroughly address this question.

The unambiguous proof for early (pre-ceramic) agricultural activities in Central Europe requires finds of cereal macroremains The lack of suchf inds in Switzerland is a consequence of two reasons. Owing to the (humid) climatic conditions resulting in very high biological activity and thus high decomposition ratesin the soils, such grains are seldom preserved in an archaeological context in Central Europe As a matter of fact, Swiss late Mesolithic archaeological excavations yielded no finds of any plants at all, except from charcoal and carbonised Corylus nutshells. Of course, this does not mean that other plant resources were not used by the late Mesolithic people. Instead, it rather mirrors poor preservation conditions and especially the complete lack of systematic archaeobotanical analyses. Given the palynological indications for agricultural activities, the inclusion ofarchaeobotanical, archaeozoological and palynological approaches is highly desirable for future archaeological investigations covering the late Mesolithic period. Indeed,cereal grains may have been occasionally charred (e.g. in orclose to a fire place). Unambiguous evidence such as cereal grains within cultural layers older than 5500 cal BC would imply the presence of a pre-ceramic Neolithic in Central Europe, which would correspond to what is currently called the late Mesolithic period.

One of the plants he names as being common is P. lanceolata, plantian (a wheat field weed). He suggests a moblile life where crops are planted and then left, which would definitely be very interesting. What really needs to be done is sift through the fire remains to find cereal grains.

Interestingly, someone else shares my view that Mesolithic Europeans could have been planting nut trees. Would this be a ‘Mesolithic revolution’?

From ‘The Cambridge World History of Food’.

During the Mesolithic, hazelnut bushes spread rapidly to many parts of Europe, as evidenced by pollen diagrams. This is in contrast to the vegetation development of the earlier interglacials. Hazelnuts are heavy, with low dispersal rates, so that it is very unlikely that the plant diffused unaided to all parts of northern Europe at the same time. Instead, it has often been assumed that hazelnuts were culturally dispersed by Mesolithic peoples (Firbas 1949: 149; Smith 1970: 81—96). Indeed, the distribution of these nuts is recorded by pollen analysis in the Mesolithic layer of Hohen Viecheln at the border of Lake Schwerin in northern Germany (Schmitz 1961: 29).

I suggest that someone takes a trip to the area around Francthi cave in Greece, and starts searching for lentil, almond, pistachio and vetch pollen. If it is absent before about 11,000 BP, that would more or less prove that those plants were imported and cultivated prior to grains, and it would place agriculture in Europe at 2,000 years earlier.

Lighter eyes means lighter skin?

While trying to locate information on whether hair colour lightens skin tone, I found a few articles suggesting that eye colour does, blue eyes particularly. Here’s a couple of studies I’ve found. From what I’ve read, it seems that several recessive genes (red hair, blue eyes) lighten skin colour. It’s not totally clear if it’s just through geographical association with other genes though.

Skin pigmentation, biogeographical ancestry and admixture mapping

Authors
Mark D. Shriver, Esteban J. Parra, Sonia Dios, Carolina Bonilla, Heather Norton, Celina Jovel, Carrie Pfaff, Cecily Jones, Aisha Massac, Neil Cameron, Archie Baron, Tabitha Jackson, George Argyropoulos, Li Jin, Clive J. Hoggart, Paul M. McKeigue, Rick A. Kittles

Ancestry informative markers (AIMs) are genetic loci showing alleles with large frequency differences between populations. AIMs can be used to estimate biogeographical ancestry at the level of the population, subgroup (e.g. cases and controls) and individual. Ancestry estimates at both the subgroup and individual level can be directly instructive regarding the genetics of the phenotypes that differ qualitatively or in frequency between populations. These estimates can provide a compelling foundation for the use of admixture mapping (AM) methods to identify the genes underlying these traits. We present details of a panel of 34 AIMs and demonstrate how such studies can proceed, by using skin pigmentation as a model phenotype. We have genotyped these markers in two population samples with primarily African ancestry, viz. African Americans from Washington D.C. and an African Caribbean sample from Britain, and in a sample of European Americans from Pennsylvania. In the two African population samples, we observed significant correlations between estimates of individual ancestry and skin pigmentation as measured by reflectometry (R2=0.21, P<0.0001 for the African-American sample and R2=0.16, P<0.0001 for the British African-Caribbean sample). These correlations confirm the validity of the ancestry estimates and also indicate the high level of population structure related to admixture, a level that characterizes these populations and that is detectable by using other tests to identify genetic structure. We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation. We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations. This work indicates that it is possible to estimate the individual ancestry of a person based on DNA analysis with a reasonable number of well-defined genetic markers. The implications and applications of ancestry estimates in biomedical research are discussed.

 
OCA2 controls eye colour, and TYR is a gene that harbours mutations for albinism. This seems to suggest that lighter eye colour could lead to lighter skin colour too. You see this in albino Africans, with partial albinism. They sometimes have blond hair and blue eyes, not the white hair and pink eyes of a full albino.

 I’m sure Razib said something about that on his blog…

	Fair skin	Medium skin	Olive skin
Blue/Blue	46.5	46.1	7.4
Blue/Brown	31.3	52.2	16.6
Brown/Brown	25.6	37.9	37.0

Please excuse the plagiarism. Full blog item here.

The paper he ’s quoting from…

A Three–Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation

We have previously shown that a quantitative-trait locus linked to the OCA2region of 15q accounts for 74% of variation in human eye color. We conducted additional genotyping to clarify the role of the OCA2locus in the inheritance of eye color and other pigmentary traits associated with skin-cancer risk in white populations. Fifty-eight synonymous and nonsynonymous exonic single-nucleotide polymorphisms (SNPs) and tagging SNPs were typed in a collection of 3,839 adolescent twins, their siblings, and their parents. The highest association for blue/nonblue eye color was found with three OCA2SNPs: rs7495174 T/C, rs6497268 G/T, and rs11855019 T/C (P values of 1.02×10^-61, 1.57×10^-96, and 4.45×10^-54, respectively) in intron 1. These three SNPs are in one major haplotype block, with TGT representing 78.4% of alleles. The TGT/TGT diplotype found in 62.2% of samples was the major genotype seen to modify eye color, with a frequency of 0.905 in blue or green compared with only 0.095 in brown eye color. This genotype was also at highest frequency in subjects with light brown hair and was more frequent in fair and medium skin types, consistent with the TGT haplotype acting as a recessive modifier of lighter pigmentary phenotypes. Homozygotes for rs11855019C/C were predominantly without freckles and had lower mole counts. The minor population impact of the nonsynonymous coding-region polymorphisms Arg305Trp and Arg419Gln associated with non-blue eyes and the tight linkage of the major TGT haplotype within the intron 1 of OCA2 with blue eye color and lighter hair and skin tones suggest that differences within the 5′ proximal regulatory control region of the OCA2 gene alter expression or messenger RNA–transcript levels and may be responsible for these associations.

And a more recent addition.

Interactions Between HERC2, OCA2 and MC1R May Influence Human Pigmentation Phenotype

Annals of Human Genetics doi:10.1111/j.1469-1809.2009.00504.x, Wojciech Branicki et al.

Human pigmentation is a polygenic trait which may be shaped by different kinds of gene–gene interactions. Recent studies have revealed that interactive effects between HERC2 and OCA2 may be responsible for blue eye colour determination in humans. Here we performed a population association study, examining important polymorphisms within the HERC2 and OCA2 genes. Furthermore, pooling these results with genotyping data for MC1R, ASIP and SLC45A2 obtained for the same population sample we also analysed potential genetic interactions affecting variation in eye, hair and skin colour. Our results confirmed the association of HERC2 rs12913832 with eye colour and showed that this SNP is also significantly associated with skin and hair colouration. It is also concluded that OCA2 rs1800407 is independently associated with eye colour. Finally, using various approaches we were able to show that there is an interaction between MC1R and HERC2 in determination of skin and hair colour in the studied population sample.

Anyone interested in this might be interested in Razibs more in depth look at this here

This is my all time number one post on this blog, about ten percent of hits have come from this. Lord only knows why but about 150 people a day look at it. Why this one?