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    No evidence for strong recent positive selection favoring the 7 repeat allele of VNTR in the DRD4 gene.
    Naka, I ; Nishida, N ; Ohashi, J ; Quintana-Murci, L (Public Library of Science (PLoS), 2011)
    The human dopamine receptor D4 (DRD4) gene contains a 48-bp variable number of tandem repeat (VNTR) in exon 3, encoding the third intracellular loop of this dopamine receptor. The DRD4 7R allele, which seems to have a single origin, is commonly observed in various human populations and the nucleotide diversity of the DRD4 7R haplotype at the DRD4 locus is reduced compared to the most common DRD4 4R haplotype. Based on these observations, previous studies have hypothesized that positive selection has acted on the DRD4 7R allele. However, the degrees of linkage disequilibrium (LD) of the DRD4 7R allele with single nucleotide polymorphisms (SNPs) outside the DRD4 locus have not been evaluated. In this study, to re-examine the possibility of recent positive selection favoring the DRD4 7R allele, we genotyped HapMap subjects for DRD4 VNTR, and conducted several neutrality tests including long range haplotype test and iHS test based on the extended haplotype homozygosity. Our results indicated that LD of the DRD4 7R allele was not extended compared to SNP alleles with the similar frequency. Thus, we conclude that the DRD4 7R allele has not been subjected to strong recent positive selection.
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    Testing the thrifty gene hypothesis: the Gly482Ser variant in PPARGC1A is associated with BMI in Tongans.
    Myles, S ; Lea, RA ; Ohashi, J ; Chambers, GK ; Weiss, JG ; Hardouin, E ; Engelken, J ; Macartney-Coxson, DP ; Eccles, DA ; Naka, I ; Kimura, R ; Inaoka, T ; Matsumura, Y ; Stoneking, M (Springer Science and Business Media LLC, 2011-01-18)
    BACKGROUND: the thrifty gene hypothesis posits that, in populations that experienced periods of feast and famine, natural selection favoured individuals carrying thrifty alleles that promote the storage of fat and energy. Polynesians likely experienced long periods of cold stress and starvation during their settlement of the Pacific and today have high rates of obesity and type 2 diabetes (T2DM), possibly due to past positive selection for thrifty alleles. Alternatively, T2DM risk alleles may simply have drifted to high frequency in Polynesians. To identify thrifty alleles in Polynesians, we previously examined evidence of positive selection on T2DM-associated SNPs and identified a T2DM risk allele at unusually high frequency in Polynesians. We suggested that the risk allele of the Gly482Ser variant in the PPARGC1A gene was driven to high frequency in Polynesians by positive selection and therefore possibly represented a thrifty allele in the Pacific. METHODS: here we examine whether PPARGC1A is a thrifty gene in Pacific populations by testing for an association between Gly482Ser genotypes and BMI in two Pacific populations (Maori and Tongans) and by evaluating the frequency of the risk allele of the Gly482Ser variant in a sample of worldwide populations. RESULTS: we find that the Gly482Ser variant is associated with BMI in Tongans but not in Maori. In a sample of 58 populations worldwide, we also show that the 482Ser risk allele reaches its highest frequency in the Pacific. CONCLUSION: the association between Gly482Ser genotypes and BMI in Tongans together with the worldwide frequency distribution of the Gly482Ser risk allele suggests that PPARGC1A remains a candidate thrifty gene in Pacific populations.
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    Drosophila Ribosomal Protein Mutants Control Tissue Growth Non-Autonomously via Effects on the Prothoracic Gland and Ecdysone
    Lin, JI ; Mitchell, NC ; Kalcina, M ; Tchoubrieva, E ; Stewart, MJ ; Marygold, SJ ; Walker, CD ; Thomas, G ; Leevers, SJ ; Pearson, RB ; Quinn, LM ; Hannan, RD ; Perrimon, N (PUBLIC LIBRARY SCIENCE, 2011-12-01)
    The ribosome is critical for all aspects of cell growth due to its essential role in protein synthesis. Paradoxically, many Ribosomal proteins (Rps) act as tumour suppressors in Drosophila and vertebrates. To examine how reductions in Rps could lead to tissue overgrowth, we took advantage of the observation that an RpS6 mutant dominantly suppresses the small rough eye phenotype in a cyclin E hypomorphic mutant (cycE(JP)). We demonstrated that the suppression of cycE(JP) by the RpS6 mutant is not a consequence of restoring CycE protein levels or activity in the eye imaginal tissue. Rather, the use of UAS-RpS6 RNAi transgenics revealed that the suppression of cycE(JP) is exerted via a mechanism extrinsic to the eye, whereby reduced Rp levels in the prothoracic gland decreases the activity of ecdysone, the steroid hormone, delaying developmental timing and hence allowing time for tissue and organ overgrowth. These data provide for the first time a rationale to explain the counter-intuitive organ overgrowth phenotypes observed for certain members of the Minute class of Drosophila Rp mutants. They also demonstrate how Rp mutants can affect growth and development cell non-autonomously.
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    I, Ya ri a bsod, am a dog: The Life and Music of a Tibetan Mendicant Singer
    ROCHE, G ; Skal dbang skyid, ; Sha bo don sgrub rdo rje, ; Sgrol ma mtsho, ; Schweickert, E ; Dpa' rtse rgyal, ; Stuart, K (Asian Highlands Perspectives, 2011)
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    Childbirth and Childcare in Rdo sbis Tibetan Township
    ROCHE, G ; Klu mo tshe ring, (Asian Highlands Perspectives, 2011)
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    Purity and Fortune in Phug sde Village Rituals
    ROCHE, G ; Sa mtsho skyid, (Asian Highlands Perspectives, 2011)
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    Javanese -ake and -akan: A Short History
    Adelaar, A (UNIV HAWAII PRESS, 2011-12-01)
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