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

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