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Background: While prions play a central role in the pathogenesis of transmissible spongiform encephalopathies, the biology of these proteins and the pathophysiology of these diseases remain largely unknown. Since no case of bovine spongiform encephalopathy (BSE) has ever been reported in buffalo despite their phylogenetic proximity to cattle, genetic differences may be driving the different susceptibilities of these two species to BSE. We thus hypothesized that differences in expression of the most recently identified member of the prion family or Shadoo (SPRN) gene may relate to these species-specific differences. Principal Findings: We first analyzed and compared the polymorphisms of the SPRN gene (~4.4 kb), including the putative promoter, coding and 39 regions, and further verified the entire ORF and putative promoter. This yielded a total of 117 fixed differences, remarkably: 1) a 12-bp insertion/deletion polymorphism in the hydrophobic domain of the cattle but not buffalo gene, introducing a four amino acid expansion/contraction in a series of 5 tandem Ala/Gly-containing repeats; 2) two fixed missense mutations (102Ser→Gly and 119Thr→Ala), and three missense mutations (92Pro.Thr/Met, 122Thr.Ile and 139Arg.Trp) in the coding region presenting different (P,0.05) genotypic and allelic frequency distributions between cattle and buffalo; and, 3) functional luciferase-reporter experiments for the predicted promoter region, consistent with a significantly higher activity in buffalo than cattle. Supporting these findings, immunoblotting revealed higher relative expression levels of Sho protein in cerebrum from buffalo than from cattle. In addition, for cattle, highest Sho expression was detected in obex, as compared to cerebrum or cerebellum. Significance: Our findings support Sho as a non-PrP specific marker for prion infections, with obex as the best tissue source for the detection of Sho in TSE rapid tests. Moreover, these discoveries may prove advantageous for further understanding the biology of prion diseases. [ABSTRACT FROM AUTHOR]

Melatonin is predominantly involved in signaling circadian and seasonal rhythms, and its synthesis is regulated by the environmental light/dark cycle. The selection pressure by geographically different environmental light/dark cycles, which is predominantly determined by sunshine duration, on the global distribution of genetic polymorphisms in the melatonin pathway is not well understood. Recent genetic association studies identified various disease-predisposition polymorphisms in this pathway. We investigated the correlations between the prevalence of these clinically important single nucleotide polymorphisms (SNPs) and sunshine duration among worldwide human populations from twelve regions in the CEPH-HGDP database rs4753426, a recently reported predisposition SNP for type 2 diabetes in the promoter of the MT2 melatonin receptor gene ( MTNR1B), which was not included in the CEPH-HGDP genotyping array, was additionally genotyped. This SNP showed a marginally significant correlation in 760 CEPH-HGDP DNA samples ( r = −0.5346, P = 0.0733), and it showed the most prominent association among the candidate melatonin pathway SNPs examined. To control for population structure, which may lead to a false positive correlation, we genotyped this SNP in a replication set of 1792 subjects from China. The correlation was confirmed among Chinese populations ( r = −0.8694, P = 0.0002), and was also statistically significant after correction of other climatic and geographical covariants in multiple regression analysis (β = −0.907, P = 1.94 × 10−5). Taken together, it suggests that the human melatonin signaling pathway, particularly MT2 melatonin receptor may have undergone a selective pressure in response to global variation in sunshine duration. [ABSTRACT FROM AUTHOR]

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Background: Several investigators have employed high throughput mitochondrial sequencing array (MitoChip) in clinical studies to search mtDNA for markers linked to cancers. In consequence, a host of somatic mtDNA mutations have been identified as linked to different types of cancers. However, closer examination of these data show that there are a number of potential pitfalls in the detection tumor-specific somatic mutations in clinical case studies, thus urging caution in the interpretation of mtDNA data to the patients. This study examined mitochondrial sequence variants demonstrated in cancer patients, and assessed the reliability of using detected patterns of polymorphisms in the early diagnosis of cancer. Methods: Published entire mitochondrial genomes from head and neck, adenoid cystic carcinoma, sessile serrated adenoma, and lung primary tumor from clinical patients were examined in a phylogenetic context and compared with known, naturally occurring mutations which characterize different populations. Results: The phylogenetic linkage analysis of whole arrays of mtDNA mutations from patient cancerous and noncancerous tissue confirmed that artificial recombination events occurred in studies of head and neck, adenoid cystic carcinoma, sessile serrated adenoma, and lung primary tumor. Our phylogenetic analysis of these tumor and control leukocyte mtDNA haplotype sequences shows clear cut evidence of mixed ancestries found in single individuals. Conclusions: Our study makes two prescriptions: both in the clinical situation and in research 1. more care should be taken in maintaining sample identity and 2. analysis should always be undertaken with respect to all the data available and within an evolutionary framework to eliminate artifacts and mix-ups. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested a probable association between the polymorphism of a microsatellite locus located in the promoter of IGF1 (Insulin-like growth factor 1) gene and the serum level of IGF1, as well as many age-related diseases. Based on these results, we hypothesized that this polymorphism may influence longevity in humans. We performed an association study in a Han Chinese population to test this hypothesis. Findings: We recruited 493 elderly Han Chinese individuals (females ≥ 94; males ≥ 90) and 425 young individuals (controls) from Dujiangyan (Sichuan province, China). The genotype distributions and allele frequencies of the microsatellite site in the elderly and control groups were compared by chi square test. Our results suggested that there was no association between the microsatellite polymorphism and longevity in our Han Chinese population. However, there were more male persons with 18/21 genotype in elderly group than that in control group (11.11 vs. 5.45%, p = 0.011). As the difference was not significant when corrected by Bonferroni method, we speculate that the 18/21 genotype can not be functional in longevity; however, it may link with the real functional loci as there is a long haplotype block embracing the microsatellite locus. Conclusions: There was no association between polymorphism of the microsatellite in promoter of IGF1 gene and longevity in our study. Future association studies containing the long haplotype block are deserved and can test our speculation of the potential linkage of 18/21 genotype and functional loci. [ABSTRACT FROM AUTHOR]

The Sichuan golden monkey ( Rhinopithecus roxellana) is a famous and beautiful endangered primate. Owing to the dearth of samples and technical limitations, previous studies could not adequately assess the levels of genetic polymorphisms in the species. To evaluate the polymorphisms further, we sequenced the entire mitochondrial control regions (D-loop) of 35 individuals from the 3 major habitats: Minshan, Qinglin, and Shennongjia. We observed many polymorphisms and estimated that the effective population size of the current total population is less than ca. 480–2300, and the time to the most recent common ancestor is ca. 4000–62,700 years. Through comparisons, we showed that the population of Rhinopithecus roxellana has a relatively higher polymorphism level than that of other endangered primates. [ABSTRACT FROM AUTHOR]

Bengal slow lorises ( Nycticebus bengalensis) and pygmy slow lorises ( Nycticebus pygmaeus) are nocturnal which creates difficulties to study them in the field. There is a scarcity of data on them and their population genetics are poorly understood. We sequenced and analyzed a partial fragment in the first hypervariable region of the mitochondrial control region or D-loop HVRI of 21 Nycticebus bengalensis and 119 N. pygmaeus from the boundary between China and Vietnam where they are sympatric. Though the sample size for Nycticebus pygmaeus is much larger, the polymorphism level is much lower than that of N. bengalensis, possibly because of (1) external gene flow from other habitats of N. bengalensis, (2) gene ingression from Sunda slow lorises ( N. coucang coucang) to N. bengalensis, (3) a skewed birth sex ratio in N. pygmaeus, and (4) a possible low survival rate of infant N. pygmaeus. Based on genetic comparisons to Nycticebus bengalensis, we propose that N. pygmaeus in southern China and northern Vietnam might have migrated from middle or southern Vietnam recently. [ABSTRACT FROM AUTHOR]

To study the mitochondrial DNA (mtDNA) polymorphisms in a total of 232 individuals from five ethnic populations (Daur, n=45; Ewenki, n=47; Korean, n=48; Mongolian, n=48; Oroqen, n=44) in northern China, we analyzed the control region sequences and typed for a number of characteristic mutations in coding regions (especially the region 14576–16047), by direct sequencing or restriction-fragment-length-polymorphism (RFLP) analysis. With the exception of 14 individuals belonging to the European-specific haplogroups R2, H, J, and T, the mtDNAs considered could be assigned into the East Asian-specific haplogroups described recently. The polymorphisms in cytochrome b sequence were found to be very informative for defining or supporting the haplogroups status of East Asian mtDNAs in addition to the reported regions 10171–10659 and 14055–14590 in our previous study. The haplogroup distribution frequencies varied in the five ethnic populations, but in general they all harbored a large amount of north-prevalent haplogroups, such as D, G, C, and Z, and thus were in agreement with their ethnohistory of northern origin. The two populations (Ewenki and Oroqen) with small population census also show concordant features in their matrilineal genetic structures, with lower genetic diversities observed. [ABSTRACT FROM AUTHOR]

In total, 1218 Chinese from twelve ethnic groups and nine Han geographic groups were screened for the mtDNA 9-bp deletion motif. The frequency of the 9-bp deletion in all samples was 14.7% but ranged from 0% to 32% in the various ethnic groups. Three individuals had a triplication of the 9-bp segment. Phylogenetic and demographic analyses of the mtDNA hypervariable segment 1 (HVS1) sequences suggest that the 9-bp deletion occurred more than once in China. The majority of the Chinese deletion haplotypes (about 90%) have a common origin as a mutational event following an initial expansion of modern humans in eastern Asia. Other deletion haplotypes and the three haplotypes with a 9-bp triplication may have arisen independently in the Chinese, presumably by replication error. HVS1 haplotype analysis suggests two possible migration routes of the 9-bp deletion in east and southeast Asia. Both migrations originated in China with one route leading to the Pacific Islands via Taiwan, the other to southeast Asia and possibly the Nicobar Islands. Along both routes of peopling, a decrease in HVS1 diversity of the mtDNA haplotypes is observed. The "Polynesian motif (16217T/C, 16247A/G, and 16261C/T)" and the 16140T/C, 16266C/A, or C/G polymorphisms appear specific to each migration route. [ABSTRACT FROM AUTHOR]

Eleven polymorphic microsatellite loci were characterized for the endangered conifer Taxus yunnanensis. Eight loci were isolated through SSR-anchored PCR, one locus was developed by cross-species amplification tests, while the last two loci were obtained from cross-species microsatellite sequences available in GenBank. Variability of these markers was tested in 48 individuals collected from its main distribution range in Southwest China. The number of alleles per locus ranged from 2 to 9, and the observed and expected heterozygosity varied from 0.000 to 0.625 and from 0.062 to 0.853, respectively. Ten of these eleven loci were significantly deviated from Hardy-Weinberg expectation, except TS07 which showed a distinct heterozygote excess. The availability of these new polymorphic microsatellite markers will provide an ideal marker system for detailed population genetics studies in T. yunnanensis and potentially also for closely related species. [ABSTRACT FROM AUTHOR]

The polymorphism of a gene or a locus is studied with increasing frequency by multiple laboratories or the same group at different times. Such practice results in polymorphism being revealed by different samples at different regions of the locus. Tests of neutrality have been widely conducted for polymorphism data but commonly used statistical tests cannot be applied directly to such data. This article provides a procedure to conduct a neutrality test and details are given for two commonly used tests. Applying the two new tests to the chemokine-receptor gene (CCR5) in humans, we found that the hypothesis that all mutations are selectively neutral cannot explain the observed pattern of DNA polymorphism. [ABSTRACT FROM AUTHOR]

To resolve the phylogeny of the autochthonous mitochondrial DNA (mtDNA) haplogroups of India and determine the relationship between the Indian and western Eurasian mtDNA pools more precisely, a diverse subset of 75 macrohaplogroup N lineages was chosen for complete sequencing from a collection of >800 control-region sequences sampled across India. We identified five new autochthonous haplogroups (R7, R8, R30, R31, and N5) and fully characterized the autochthonous haplogroups (R5, R6, N1d, U2a, U2b, and U2c) that were previously described only by first hypervariable segment (HVS-I) sequencing and coding-region restriction-fragment-length polymorphism analysis. Our findings demonstrate that the Indian mtDNA pool, even when restricted to macrohaplogroup N, harbors at least as many deepest-branching lineages as the western Eurasian mtDNA pool. Moreover, the distribution of the earliest branches within haplogroups M, N, and R across Eurasia and Oceania provides additional evidence for a three-founder-mtDNA scenario and a single migration route out of Africa. [ABSTRACT FROM AUTHOR]