Archivi categoria: PLOS

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

by Christopher H. Chandler, Sudarshan Chari, Alycia Kowalski, Lin Choi, David Tack, Michael DeNieu, William Pitchers, Anne Sonnenschein, Leslie Marvin, Kristen Hummel, Christian Marier, Andrew Victory, Cody Porter, Anna Mammel, Julie Holms, Gayatri Sivaratnam, Ian Dworkin

For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development) of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis.

Tratto da: www.plos.org.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

by Zarko Manojlovic, Austin Christofferson, Winnie S. Liang, Jessica Aldrich, Megan Washington, Shukmei Wong, Daniel Rohrer, Scott Jewell, Rick A. Kittles, Mary Derome, Daniel Auclair, David Wesley Craig, Jonathan Keats, John D. Carpten

Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups. Of interest, BCL7A, BRWD3, and AUTS2 demonstrate significantly higher mutation frequencies among AA cases. These genes are all involved in translocations in B-cell malignancies. Moreover, we detected a significant difference in mutation frequency of TP53 and IRF4 with frequencies higher among CA cases. Our study provides rationale for interrogating diverse tumor cohorts to best understand tumor genomics across populations.

Tratto da: www.plos.org.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

Human trafficking and exploitation: A global health concern

by Cathy Zimmerman, Ligia Kiss

In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

Tratto da: www.plos.org.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

Sexual exploitation of unaccompanied migrant and refugee boys in Greece: Approaches to prevention

by Julie Freccero, Dan Biswas, Audrey Whiting, Khaled Alrabe, Kim Thuy Seelinger

In this essay, Julie Freccero and colleagues discuss resources to prevent the sexual exploitation of unaccompanied and separated refugee boys in Greece.

Tratto da: www.plos.org.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

Labour trafficking: Challenges and opportunities from an occupational health perspective

by Elena Ronda-Pérez, Bente E. Moen

In this essay for the collection on Human Trafficking, Exploitation, and Health, Elena Ronda-Perez and colleague discuss ways occupational health services can detect and address labour trafficking.

Tratto da: www.plos.org.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

Extreme exploitation in Southeast Asia waters: Challenges in progressing towards universal health coverage for migrant workers

by Rapeepong Suphanchaimat, Nareerut Pudpong, Viroj Tangcharoensathien

Rapeepong Suphanchaimat and colleagues present the plight of migrant workers in the fishing industry in Southeast Asia and discuss challenges in providing for their health and safety.

Tratto da: www.plos.org.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.