Comprehensive candidate gene study highlights UGT1A and BNC2 as new genes determining continuous skin color variation in Europeans

Natural variation in human skin pigmentation is primarily due to genetic causes rooted in recent evolutionary history. Genetic variants associated with human skin pigmentation confer risk of skin cancer and may provide useful information in forensic investigations. Almost all previous gene-mapping studies of human skin pigmentation were based on categorical skin color information known to oversimplify the continuous nature of human skin coloration. We digitally quantified skin color into hue and saturation dimensions for 5,860 Dutch Europeans based on high-resolution skin photographs. We then tested an extensive list of 14,185 single nucleotide polymorphisms in 281 candidate genes potentially involved in human skin pigmentation for association with quantitative skin color phenotypes. Confirmatory association was revealed for several known skin color genes including HERC2, MC1R, IRF4, TYR, OCA2, and ASIP. We identified two new skin color genes: genetic variants in UGT1A were significantly associated with hue and variants in BNC2 were significantly associated with saturation. Overall, digital quantification of human skin color allowed detecting new skin color genes. The variants identified in this study may also contribute to the risk of skin cancer. Our findings are also important for predicting skin color in forensic investigations.     

部分水产养殖动物性别控制基因的研究进展

动物的性别是受遗传或环境等因素控制的。自从在哺乳动物中发现了性别决定基因SRY后,还发现了许多其他与性别控制和性腺发育相关的基因。由于海水养殖动物的性别控制技术在遗传育种和生产中十分重要,因此利用现代分子生物技术研究性别控制的基因成为热点。本文综述了鱼类、锯缘青蟹、海龟和海胆等水产养殖动物性别控制基因的研究进展。     

Genetic basis and biotechnological manipulation of sexual dimorphism and sex determination in fish

Aquaculture has made an enormous contribution to the world food production,especially to the sustainable supply of animal proteins.The utility of diverse reproduction strategies in fish,such as the exploiting use of unisexual gynogenesis,has created a typical case of fish genetic breeding.A number of fish species show substantial sexual dimorphism that is closely linked to multiple economic traits including growth rate and body size,and the efficient development of sex-linked genetic markers and sex control biotechnologies has provided significant approaches to increase the production and value for commercial purposes.Along with the rapid development of genomics and molecular genetic techniques,the genetic basis of sexual dimorphism has been gradually deciphered,and great progress has been made in the mechanisms of fish sex determination and identification of sex-determining genes.This review summarizes the progress to provide some directive and objective thinking for further research in this field.     

Genetics of color of the ornamental carp: inheritance of underlying dark coloration]

In ornamental carps from the collection of the Experimental Station, All-Russia Research Institute of Fresh-Water Fisheries, fish with a dirty dark tint of body color among orange and white fish were found. This coloration was shown to be due to the presence of black pigment cells in the lower skin layer. In the outer skin layers these cells were almost entirely absent. This color type was found to be determined by the presence of at least one of alleles B1' or B2' of digenic system B1, B2, which is responsible for the development of melanophores in fish skin. Each of the genes of this digenic system is represented by three alleles with the following order of dominance: B > B' > b.     

Quantitative genetics of human skin color

Skin color has long been of interest to human geneticists and often used as an example of a human quantitative trait under relatively wellunderstood genetic control. Although the basic biology of melanin production and the method of measurement are areas in which skin color studies are fairly well advanced, compared to other quantitative traits, the evolutionary significance and mode of inheritance are still being debated. In view of the many steps involved in the production and dispersion of melanin and the large number of loci involved in coat color of laboratory animals, it is suggested that genetic control of human skin color must be fairly complex. Studies that have found evidence for relatively few loci effecting the differences between racial groups may either be using inappropriate methods, or they may be concentrating attention on only that portion of genetic variability that distinguishes between major world groups, particularly blacks and whites. Genetic analysis of intermediate groups and pedigree analysis of rare pigmentation conditions may yield more information on skin color genetics.     

Apoptosis in skin pigment cells of the medaka, Oryzias latipes (Teleostei), during long-term chromatic adaptation: the role of sympathetic innervation

Many teleost fish can adapt their body color to a background color by changing the morphology and density of their skin pigment cells. Melanophore density in fish skin decreases during long-term adaptation to a white background. Although cell death, especially apoptosis, is thought to be involved in these morphological changes, there are no data clearly supporting this mechanism. Using medaka fish, Oryzias latipes, we observed that, on a white background, melanophore size was reduced first and this was followed by a decrease in melanophore density caused by gradual cell death. The process of cell death included loss of cell activity, cell fragmentation, phagocytosis of the fragments, and clearance via the epidermis. Apoptosis was assessed by the appearance of phosphatidylserine on the cell surface of melanophores that had lost motile activity, and DNA fragments involved in cell fragmentation were detected by the TUNEL (TDT-mediated dUTP-biotin nick end-labeling) assay. However, when chemically denervated fish were used, although melanophore size was reduced as expected, cell death was suppressed even on a white background. In skin tissue culture, apoptosis in melanophores was stimulated significantly by norepinephrine, but not by melanin-concentrating hormone. These results indicate that melanophore density decreases by apoptosis, and suggest that sympathetic innervation has an important role in the regulation of apoptosis in melanophores. In analogous fashion, leucophores showed a significant decrease in density with an increase of cell death on a black background. We suggest that apoptosis regulates the balance of pigment cells in the skin of medaka fish to adapt their body color to a particular background.     

Molecular players involved in temperature-dependent sex determination and sex differentiation in Teleost fish

The molecular mechanisms that underlie sex determination and differentiation are conserved and diversified. In fish species, temperature-dependent sex determination and differentiation seem to be ubiquitous and molecular players involved in these mechanisms may be conserved. Although how the ambient temperature transduces signals to the undifferentiated gonads remains to be elucidated, the genes downstream in the sex differentiation pathway are shared between sex-determining mechanisms. In this paper, we review recent advances on the molecular players that participate in the sex determination and differentiation in fish species, by putting emphasis on temperature-dependent sex determination and differentiation, which include temperature-dependent sex determination and genetic sex determination plus temperature effects. Application of temperature-dependent sex differentiation in farmed fish and the consequences of temperature-induced sex reversal are discussed.     

用模式生物青鳉概观硬骨鱼性别决定及性分化研究进展

鱼类性别决定和性分化呈多元性,既有雌雄同体也有雌雄异体。性腺的雌雄性分化过程受遗传和环境因素(如温度、光照、激素和pH值等)影响,具有可逆可塑性。随着生物技术和基因组学的迅速发展,近年来脊椎动物性别决定和性分化的研究有了重大进展和显著突破。本文通过聚焦青鳉及其他硬骨鱼纲保守存在的dmrt1、gsdf、amh等雄性因子,探讨硬骨鱼普遍存在的雌雄性别可塑可逆信号通路,并介绍了新的基因组编辑和性控育种技术,为单性选育等水产养殖技术的研发提供参考。     

Quantitative genetic analysis of skin reflectance: a multivariate approach.

Skin color is a polygenically determined quantitative trait. Although it has been used extensively in studies of between-population variation, there have been relatively few studies of the inheritance of skin color. In this article we use measurements on 359 members of the Jirel population of eastern Nepal to assess the heritabilities and additive genetic correlations of three skin reflectance measures. Skin color was measured at the upper inner arm site at three wavelengths. A maximum likelihood approach was used to estimate sex and age effects on skin reflectance, heritabilities, and phenotypic variances at each wavelength and both additive genetic and environmental correlations between wavelengths. This technique incorporated information from 36 pedigrees with 2-25 members and 173 independent individuals. Likelihood ratio tests were used to assess the significance of specific variance/covariance components. The results indicate that skin reflectances are moderately heritable at all three wavelengths. The pairwise phenotypic correlations ranged from 0.76 to 0.88. The observed additive genetic correlations were not significantly different from 1.00, suggesting that the same loci influence variation at each wavelength. This evidence for relatively complete pleiotropy implies that measurements at multiple wavelengths yield little additional genetic information, although they may be useful for reducing measurement error. Based on estimates of the genetic and phenotypic covariance matrices, we determined that skin reflectance measurements are expected to provide only as much information for assessing local between-population genetic variation as a single two-allele polymorphic marker. Therefore microevolutionary studies based on skin color variation should be viewed with caution.     

A comparative view on sex determination in medaka

In fish, an amazing variety of sex determination mechanisms are known, ranging from hermaphroditism to gonochorism and from environmental to genetic sex determination. This makes fish especially suited for studying sex determination from the evolutionary point of view. In several fish groups, different sex determination mechanisms are found in closely related species, and evolution of this process is still ongoing in recent organisms. The medaka (Oryzias latipes) has an XY-XX genetic sex determination system. The Y-chromosome in this species is at an early stage of evolution. The molecular differences between X and Y are only very subtle and the Y-specific segment is very small. The sex-determining region has accumulated duplicated sequences from elsewhere in the genome, leading to recombinational isolation. The region contains a candidate for the male sex-determining gene named dmrt1bY. This gene arose through duplication of an autosomal chromosome fragment of linkage group 9. While all other genes degenerated, dmrt1bY is the only functional gene in the Y-specific region. The duplication leading to dmrt1bY occurred recently during evolution of the genus Oryzias. This suggests that different genes might be the master sex-determining gene in other fish.     

Quantitative Genetic Analyses of Male Color Pattern and Female Mate Choice in a Pair of Cichlid Fishes of Lake Malawi,East Africa

The traits involved in sexual selection, such as male secondary sexual characteristics and female mate choice, often co-evolve which can promote population differentiation. However, the genetic architecture of these phenotypes can influence their evolvability and thereby affect the divergence of species. The extraordinary diversity of East African cichlid fishes is often attributed to strong sexual selection and thus this system provides an excellent model to test predictions regarding the genetic architecture of sexually selected traits that contribute to reproductive isolation. In particular, theory predicts that rapid speciation is facilitated when male sexual traits and female mating preferences are controlled by a limited number of linked genes. However, few studies have examined the genetic basis of male secondary sexual traits and female mating preferences in cichlids and none have investigated the genetic architecture of both jointly. In this study, we artificially hybridized a pair of behaviorally isolated cichlid fishes from Lake Malawi and quantified both melanistic color pattern and female mate choice. We investigated the genetic architecture of both phenotypes using quantitative genetic analyses. Our results suggest that 1) many non-additively acting genetic factors influence melanistic color patterns, 2) female mate choice may be controlled by a minimum of 1–2 non-additive genetic factors, and 3) F₂ female mate choice is not influenced by male courting effort. Furthermore, a joint analysis of color pattern and female mate choice indicates that the genes underlying these two traits are unlikely to be physically linked. These results suggest that reproductive isolation may evolve rapidly owing to the few genetic factors underlying female mate choice. Hence, female mate choice likely played an important role in the unparalleled speciation of East African cichlid fish.     

Transformer基因与果蝇和线虫的性别决定

黑腹果蝇(Drosophila melanogaster)和秀丽隐杆线虫（Caeborhabditis elegans）的性别决定的问题已研究得比较详细,且transformer基因是这两种生物性别决定中最重要的基因之一,其有关的性别决定研究在近几年取得了很大的进展。本文就线虫和果蝇的transformer基因及其相关基因的特性与功能进行了特别介绍,并在此基础上对其性别决定的分子机制进行初步的比较和分析。Abstract : Sex determination of Drosophila melanogaster and Caeborhabditis elegans has been known in detail. Great progress, is achieved in recent years, is the research of transformer genes, which are those of most important genes in sex determination in both species. In this paper, molecular character, genetic function and the relative genes of transformer genes are particularly described. On the basis,a primary compariso and analysis between the molecular mechanism of sex determination in C.elegans and D. melanogaster are presented.     

Sexual determination and differentiation in teleost fish

The present work reviews the latest information on the cellular, molecular and physiological aspects of sexual determination and differentiation in teleost fish. The group exhibits a large variety of mechanisms of sexual determination. These may be genetic, or depend on environmental conditions such as temperature, pH, and social factors, all of which can influence the proportion of the sexes. Additionally, sex steroids play an important role in the regulation of sexual differentiation. The patterns of gonadal sexual differentiation are diverse, and species may be hermaphroditic or gonochoristic, some of the latter displaying juvenile hermaphroditism. In recent years, several genes involved in the sexual determination and differentiation pathways in vertebrates, particularly in mammals, have also been characterized in teleosts. Conserved as well as diversified functions have been proposed.     

Genetic governance: The risks,oversight and regulation of genetic databases in the UK

Increasing scientific and commercial interest is being paid to the creation of large population-based genetic databases to study the relationship between genes and disease. This paper will use ideas from the sociology of technology to look at the network of actors involved in the production, use and commercial exploitation of human genetic data, the social and ethical issues posed by genetic databases and the development of new governance arrangements in this domain. It will be argued that we are witnessing the creation of a new type of research system in the field of human genetics, which also forms the centre of an emerging market for personal and population-based genetic information. Some proposals for improving the governance of human genetic data in the UK will be offered in conclusion.     

Human pigmentation genetics: the difference is only skin deep

There is no doubt that visual impressions of body form and color are important in the interactions within and between human communities. Remarkably, it is the levels of just one chemically inert and stable visual pigment known as melanin that is responsible for producing all shades of humankind. Major human genes involved in its formation have been identified largely using a comparative genomics approach and through the molecular analysis of the pigmentary process that occurs within the melanocyte. Three classes of genes have been examined for their contribution to normal human color variation through the production of hypopigmented phenotypes or by genetic association with skin type and hair color. The MSH cell surface receptor and the melanosomal P-protein are the two most obvious candidate genes influencing variation in pigmentation phenotype, and may do so by regulating the levels and activities of the melanogenic enzymes tyrosinase, TRP-1 and TRP-2. BioEssays 20 :712–721, 1998.© 1998 John Wiley & Sons, Inc.     

Genetic variation among populations of the Antarctic toothfish: evolutionary insights and implications for conservation

Commercial fishing is having an increasingly negative impact on marine biodiversity, with over 70% of the world's fish stocks being fully exploited and, in many cases, overexploited. On top of this, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) has granted commercial fishing permits in the most remote marine environment on earth, the high-latitude Southern Ocean. The primary target of these new commercial fishing ventures is the large pelagic piscivorous predator, the Antarctic toothfish (Dissostichus mawsoni). Unfortunately, little information is available on the demography, genetics, or life history of this large fish. Without such information we have little idea as to the effects of commercial fishing on the population structure and survival of this species. In this study, we focus on patterns of genetic diversity within and between geographically disparate populations of the Antarctic toothfish, using randomly amplified polymorphic DNA markers. Results of our study showed high levels of genetic similarity within and between populations. Despite high levels of genetic similarity, genetic analyses detected significant population structure, including fixed differences among populations, a significant fixation index (Fst) and between-population differentiation via a Mantel test. From a conservation perspective, low levels of genetic diversity may be indicative of relatively small populations that would not be able to withstand heavy commercial fishing pressures. Given that there is evidence for significant genetic structure, it will be important to manage these fisheries in a manner that will help prevent the loss of unique genetic variation from regional overfishing.