A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals

Methods We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P < 0.001). The variant was associated with heavy smoking (> 20 CPD) [odds ratio (OR) = 1.13, 95% confidence interval (CI) 0.96-1.34, P = 0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P < 0.0001]. The strong association between the variant and LC risk (OR = 1.30, 95% CI 1.23-1.38, P = 1 x 10(-18)), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR = 1.27, 95% CI 1.19-1.35, P = 5 x 10(-13)). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P = 0.02). The association was also noted in UADT cancers (OR = 1.08, 95% CI 1.01-1.15, P = 0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour. Conclusions This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.

Whole-Genome Characterization of Human and Simian Immunodeficiency Virus Intrahost Diversity by Ultradeep Pyrosequencing

Rapid evolution and high intrahost sequence diversity are hallmarks of human and simian immunodeficiency virus (HIV/SIV) infection. Minor viral variants have important implications for drug resistance, receptor tropism, and immune evasion. Here, we used ultradeep pyrosequencing to sequence complete HIV/SIV genomes, detecting variants present at a frequency as low as 1%. This approach provides a more complete characterization of the viral population than is possible with conventional methods, revealing low-level drug resistance and detecting previously hidden changes in the viral population. While this work applies pyrosequencing to immunodeficiency viruses, this approach could be applied to virtually any viral pathogen.

Revision of the new wandering spider genus Ohvida and taxonomic remarks on Celaetycheus Simon, 1897 (Araneae: Ctenidae)

The new ctenid genus Ohvida is proposed to include eight species: Ohvida fulvorufa (Franganillo, 1931) comb. nov. (type species) (=Celaetycheus cabriolatus Franganillo, 1930 syn. nov.; = C. cabriolatus pardosiformis Franganillo, 1930 syn. nov.; = C. fulvorufus afoliatus Franganillo, 1931 syn. nov.), O. isolata (Bryant, 1940) comb. nov., O. vernalis (Bryant, 1940) comb. nov., O. brevitarsus (Bryant, 1940) comb. nov., O. coxanus (Bryant, 1940), comb. nov., and three new species, O. turquino sp. nov. (all species from Cuba), and O. andros sp. nov. and O. bimini sp. nov. (both species from The Bahamas). Species of Ohvida differ from all other ctenid spiders by the presence of a retrodorsal projection on the cymbium of the male pedipalp and by a basal position of the lateral spurs on the female epigyne. The genus Celaetycheus Simon, 1897 is reviewed to only include its type species, C. flavostriatus Simon, 1897 from Brazil. We propose the following synonyms and new combinations: Ctenus ottleyi (Petrunkevitch, 1930) (= Celaetycheus strenuus Bryant, 1942 syn. nov. and C. modestus Bryant, 1942 syn. nov.); Ctenus delesserti (Caporiacco, 1947) comb. nov., and Leptoctenus paradoxus (F.O. P.-Cambridge, 1900) comb. nov. Celaetycheus modestus Bryant, 1942 is considered incertae sedis.

Review and cladistic analysis of the Neotropical tarantula genus Ephebopus Simon 1892 (Araneae : Theraphosidae) with notes on the Aviculariinae

The tarantula genus Ephebopus Simon 1892 is reviewed and includes the type species, E. murinus (Walckenaer 1837), and E. uatuman Lucas, Silva & Bertani 1992, E. cyanognathus West & Marshall 2000, E. rufescens West & Marshall 2000 and Ephebopus foliatus, sp. nov., from Guyana. Ephebopus violaceus Mello-Leitao 1930 is transferred to Tapinauchenius Ausserer, where it is a senior synonym of Tapinauchenius purpureus Schmidt 1995 new synonymy. Ephebopus fossor Pocock 1903 is considered a nomen dubium. Ephebopus occurs in northeastern South America where it is known only from Brazil, Guyana, Suriname, and French Guiana. Spiders of the genus are generally fossorial; however, Ephebopus murinus has a developmental stage that is arboreal. A cladistic analysis of the Theraphosidae retrieves the Aviculariinae as monophyletic, including Avicularia Lamarck, Iridopelma Pocock 1901, Pachistopelma Pocock 1901, Tapinauchenius, Psalmopoeus Pocock, Ephebopus, Stromatopelma Karsch and Heteroscodra Pocock, having as a synapomorphy the well-developed scopulae on tarsi and metatarsi I-II that is very laterally extended.

Revalidation and revision of the genus Magulla Simon 1892 (Araneae, Mygalomorphae, Theraphosidae)

The genus Magulla Simon 1892 is revalidated and redescribed. The female of the type species M. obesa Simon 1892 is redescribed and the male is described for the first time. Magulla janeirus (Keyserling 1891) is considered a valid species. Magulla symmetrica Bucherl 1949 is transferred to Plesiopelma Pocock 1901, and considered a junior synonym of P. insulare (Mello-Leitao 1923). Additionally, two new species are described from Brazil: M. buecherli n. sp. from Ilhabela, Sao Paulo and M. brescoviti n. sp. from Sao Francisco de Paula, Rio Grande do Sul.

A revision of the spider genera Chaetopelma ausserer 1871 and Nesiergus simon 1903 (Araneae, theraphosidae, ischnocolinae)

Chaetopelma Ausserer 1871 and Nesiergus Simon 1903 are revised. Cratorrhagus Simon 1891 is considered a junior synonym of Chaetopelma. Cratorrhagus tetramerus (Simon 1873) and the female of Cratorrhagus concolor (Simon 1873) are conspecific with C. olivaceum (C. L. Koch 1841). Ischnocolus gracilis Ausserer 1871, Ischnocolus syriacus Ausserer 1871, Chaetopelma shabati Hassan 1950 and Ischnocolus jerusalemensis Smith 1990 are also treated here as junior synonyms of C. olivaceum. Chaetopelma adenense Simon 1890 is proposed as a junior synonym of Ischnocolus jickelii L. Koch 1875. Chaetopelma gardineri Hirst 1911 is transferred to Nesiergus. Hence, Chaetopelma comprises three valid species: C. olivaceum (C. L. Koch 1841); C. karlamani Vollmer 1997; C. concolor (Simon 1873) n. comb. from the Middle East and northeastern Africa. Nesiergus, which appears endemic to the Seychelles archipelago, now comprises three valid species: N. gardineri (Hirst 1911) n. comb.; N. halophilus Benoit 1978; N. insulanus Simon 1903.