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1.
J Med Genet ; 50(5): 298-308, 2013 May.
Article in English | MEDLINE | ID: mdl-23505323

ABSTRACT

BACKGROUND: The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. METHODS AND FINDINGS: We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein gene (p=2.43×10(-08)). Furthermore, three European loci for TGs (APOA5, GCKR and LPL), and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We used cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalised to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. CONCLUSIONS: This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; used the interpopulation heterogeneity to significantly restrict three previously known European GWA signals, and surveyed whether the European lipid GWA SNPs extend to the Mexican population.


Subject(s)
Apolipoproteins A/genetics , Genetic Loci/genetics , Hypertriglyceridemia/genetics , Hypoalphalipoproteinemias/genetics , Indians, North American/genetics , Triglycerides/genetics , Apolipoprotein A-V , Apolipoproteins A/blood , Genome-Wide Association Study , Genotype , Humans , Hypertriglyceridemia/ethnology , Hypoalphalipoproteinemias/ethnology , Linkage Disequilibrium , Membrane Proteins/genetics , Membrane Transport Proteins , Mexico , Polymorphism, Single Nucleotide/genetics , Triglycerides/blood , White People/genetics
2.
Proc Biol Sci ; 279(1734): 1684-90, 2012 May 07.
Article in English | MEDLINE | ID: mdl-22113030

ABSTRACT

We tested the hypothesis that mate choice is responsible for countergradient variation in the sexual coloration of Trinidadian guppies (Poecilia reticulata). The nature of the countergradient pattern is that geographical variation in the carotenoid content of the orange spots of males is counterbalanced by genetic variation in drosopterin production, resulting in a relatively uniform pigment ratio. A female hue preference could produce this pattern, because hue is the axis of colour variation most directly affected by the pigment ratio. To test this hypothesis, we crossed two populations differing in drosopterin production and produced an F(2) generation with variable drosopterin levels. When the carotenoid content of the orange spots was held constant, female guppies preferred males with intermediate drosopterin levels. This shows that females do not simply prefer males with greater orange spot pigment content; instead, the ratio of the pigments also affects male attractiveness. To our knowledge, this is the first direct evidence for a hypothesized agent of countergradient sexual selection.


Subject(s)
Genetic Variation , Mating Preference, Animal/physiology , Pigmentation/physiology , Poecilia/physiology , Sexual Behavior, Animal/physiology , Animals , Carotenoids/metabolism , Female , Male , Pigmentation/genetics , Poecilia/genetics , Poecilia/metabolism , Pteridines/metabolism , Sex Characteristics
3.
BMC Biol ; 6: 10, 2008 Feb 14.
Article in English | MEDLINE | ID: mdl-18275614

ABSTRACT

BACKGROUND: Adaptive radiation, the evolution of ecological and phenotypic diversity from a common ancestor, is a central concept in evolutionary biology and characterizes the evolutionary histories of many groups of organisms. One such group is the Mustelidae, the most species-rich family within the mammalian order Carnivora, encompassing 59 species classified into 22 genera. Extant mustelids display extensive ecomorphological diversity, with different lineages having evolved into an array of adaptive zones, from fossorial badgers to semi-aquatic otters. Mustelids are also widely distributed, with multiple genera found on different continents. As with other groups that have undergone adaptive radiation, resolving the phylogenetic history of mustelids presents a number of challenges because ecomorphological convergence may potentially confound morphologically based phylogenetic inferences, and because adaptive radiations often include one or more periods of rapid cladogenesis that require a large amount of data to resolve. RESULTS: We constructed a nearly complete generic-level phylogeny of the Mustelidae using a data matrix comprising 22 gene segments (approximately 12,000 base pairs) analyzed with maximum parsimony, maximum likelihood and Bayesian inference methods. We show that mustelids are consistently resolved with high nodal support into four major clades and three monotypic lineages. Using Bayesian dating techniques, we provide evidence that mustelids underwent two bursts of diversification that coincide with major paleoenvironmental and biotic changes that occurred during the Neogene and correspond with similar bursts of cladogenesis in other vertebrate groups. Biogeographical analyses indicate that most of the extant diversity of mustelids originated in Eurasia and mustelids have colonized Africa, North America and South America on multiple occasions. CONCLUSION: Combined with information from the fossil record, our phylogenetic and dating analyses suggest that mustelid diversification may have been spurred by a combination of faunal turnover events and diversification at lower trophic levels, ultimately caused by climatically driven environmental changes. Our biogeographic analyses show Eurasia as the center of origin of mustelid diversity and that mustelids in Africa, North America and South America have been assembled over time largely via dispersal, which has important implications for understanding the ecology of mustelid communities.


Subject(s)
Genetic Variation , Multigene Family , Mustelidae/genetics , Phylogeny , Animals , Bayes Theorem , Ecology , Genetic Speciation , Likelihood Functions , Mustelidae/classification , Sequence Analysis, DNA
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