Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants

Influence of the Pseudophyllidean Cestode \u3ci\u3eSchistocephalus solidus\u3c/i\u3e on Oocyte Development in the Threespine Stickleback \u3ci\u3eGasterosteus aculeatus\u3c/i\u3e

The objective of this study was to investigate the means by which Schistocephalus solidus might reduce annual fecundity in female threespine stickleback fish (Gasterosteus aculeatus) through processes of oocyte development. Histological examinations of specimens from one lake in Alaska in 2000 and 2001 were used to analyse the effects of S. solidus on recruitment of primary growth oocytes into vitellogenesis, atresia of vitellogenic oocytes, and the interspawning interval. The ratio of primary growth to late secondary growth (late vitellogenic) oocytes was significantly greater (P\u3c0.01) among infected fish than uninfected ones in early-season samples from 2000 and 2001, revealing a decrease in recruitment of oocytes from primary growth into vitellogenic oocytes among infected females. The difference was marginally non-significant (P=0.087) in a mid-season sample from 2001 due to reductions in the entire pool of vitellogenic (early and late secondary growth) oocytes recruited prior to the spawning season in this determinate-fecundity species. Atresia among all vitellogenic oocytes was low and did not differ between infected and uninfected females. Histological estimations of the interspawning interval using post-ovulatory follicles showed no significant differences between infected and uninfected fish, suggesting that the number of spawnings in stickleback females each spawning season is unaffected by S. solidus infection. Thus, annual fecundity appears to be reduced only through recruitment of oocytes into vitellogenesis

Interspawning Interval of Wild Female Three-Spined Stickleback \u3ci\u3eGasterosteus aculeatus\u3c/i\u3e in Alaska

The interspawning interval, or spawning frequency, of wild three-spined stickleback, Gasterosteus aculeatus, was estimated using histological examination of postovulatory follicles (POF). Females in Alaskan lakes appeared to have as much as a 48 h delay between ovulation and ovoposition, yet the POF method could still be used to estimate the interspawning interval. In two Alaskan lakes the interspawning interval was estimated to range from 2.2 to 7.8 days among individual female G. aculeatus. These estimates were consistent with the range (2.5 to 5 days) of previous estimates among individual females from laboratory observations of spawning G. aculeatus, as well as anecdotal accounts of spawning intervals reported from wild populations in Canada (5-10 days). The interspawning interval of females increased during the course of the spawning season in Alaska, showing that the majority of female spawning activity occurred during the earliest portion of the approximate 6-week reproductive season. The increased interspawning interval appears to be related to a previously reported decrease in body condition in reproductive females during the breeding season. Thus, female G. aculeatus may be unable to sustain the initial rate of reproduction as energy stores that support the rapid growth of vitellogenic oocytes are depleted. (C) 2009 The Authors Journal compilation (C) 2009 The Fisheries Society of the British Isle

Predicting future from past: The genomic basis of recurrent and rapid stickleback evolution

Similar forms often evolve repeatedly in nature, raising long-standing questions about the underlying mechanisms. Here, we use repeated evolution in stickleback to identify a large set of genomic loci that change recurrently during colonization of freshwater habitats by marine fish. The same loci used repeatedly in extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Marked genotypic and phenotypic changes arise within 5 years, facilitated by standing genetic variation and linkage between adaptive regions. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwin's finches, suggesting that similar features are important for evolution across diverse taxa. © 2021 American Association for the Advancement of Science. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Reproduction of a South American population of pumpkinseed sunfish Lepomis gibbosus (Linnaeus) (Osteichthyes, Centrarchidae): a comparison with the European and North American populations

The reproductive biology of the introduced pumpkinseed sunfish Lepomis gibbosus (Linnaeus, 1758) in the Custódio's Dam, rio Doce high basin, state of Minas Gerais, Brazil was studied from February/2001 to March/2002 and compared with introduced and native populations. Reproduction occurred almost along the entire period of study with a high frequency of fishes in the advanced ripening/mature and spawned/spent stages. The microscopic analyses indicated that the pumpkinseed sunfish presents multiple spawning. The egg diameter of the Brazilian population is similar to the Spanish, Greek and American ones. The standard length at maturity and the gonadosomatic index of the introduced populations are smaller when compared with native ones. The spawning season of the Brazilian population was the longest among all comparisons made in the present work.<br>Estudou-se de fevereiro/2001 a março/2002 a biologia reprodutiva da exótica perca-sol Lepomis gibbosus (Linnaeus, 1758) na represa do Custódio, bacia do alto rio Doce, Brasil, comparando-a à de populações exóticas e nativas. A reprodução ocorreu praticamente ao longo de todo o período de estudo e a análise microscópica de ovários indicou desova do tipo parcelada para a espécie. O diâmetro ovocitário da população brasileira é semelhante à espanhola, grega e americana. O comprimento padrão na maturidade e o índice gonadossomático de populações introduzidas são menores do que as nativas. O período de desova da população brasileira foi o maior dentre todas as populações analisadas no presente trabalho