For the 2012 American Society for Human Genetics conference in San Francisco, we are highlighting a selection of recently published articles in the area. In the last two years, PLOS ONE has published over 700 articles on human genetics; the eight summarized below are among the top 5% with regard to post-publication citations, HTML views, PDF downloads, and bookmarking.
Two of these papers address the genetic underpinnings of Alzheimer disease. By mining genetic data, Jones et al. linked two physiological processes, cholesterol metabolism and the innate immune response, to late-onset Alzheimer disease development. In a paper published in September of this year, Jun et al. discovered a correlation between the presence of cataracts and Alzheimer disease, and identified genetic variations in the gene encoding for the δ-catenin protein that may be the link between these two conditions.
Looking at another eye disorder, Nakano et al. investigated the genetic component of glaucoma. Their research identified genetic variations among people of Japanese ancestry that are associated with certain types of glaucoma.
Another paper looked at the potential role of epigenetic modification in type 2 diabetes. Specifically, Bell et al. compared DNA from healthy women and women with type 2 diabetes and examined variations in DNA methylation, a chemical modification to the DNA that affects gene expression. The analysis revealed significant methylation differences in regions of DNA previously associated with type 2 diabetes, suggesting that variations in DNA methylation may play a role in the disease.
Two studies considered variations in the number of repeats of specific DNA sequences, which can affect disease pathology and even drive evolution. Valsesia et al. investigated DNA copy number variations and their effect on gene expression in seven different melanoma cell lines. Their research identified candidate genes and molecular pathways involved in metastatic melanoma. Zhang et al. compared the performance of four software programs in detecting copy number variations in DNA sequences longer than 1,000 bases. The authors found inconsistency even among the most established programs, emphasizing the work that still needs to be done in this area.
Another paper addressed the issue of chromosome translocation, or the abnormal rearrangement of parts of chromosomes. In a collaboration between biologists and physicists, Engreitz et al. showed that the three-dimensional organization of DNA in the cell nucleus may help explain certain chromosomal translocations linked to human disease.
Finally, using data from the Human Genome Diversity Project, Kirin et al. profiled the lengths and frequencies of DNA sequences that are identical on maternal and paternal chromosomes. This large-scale analysis allowed the authors to make conclusions about historic and contemporary patterns of intra-communal parentage in different human populations.
If you are at the ASHG, we hope that you stop by the PLOS booth and meet some of the PLOS staff. We will be at booth # 1606. Also, if you have published in PLOS ONE, we have a stylish PLOS ONE author t-shirt to give you. We look forward to seeing you there.
Acknowledgments: Thank you to Martin Fenner for helping us with the article-level metrics analysis. Thank you to Eric Martens and Matt Hodgkinson for designing the literature search and helping analyze the final results. Finally, thank you to Camron Assadi for coordinating our efforts.
Image: Valsesia A, Rimoldi D, Martinet D, Ibberson M, Benaglio P, et al. (2011) Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma. PLoS ONE 6(4): e18369. doi:10.1371/journal.pone.0018369
Bell CG, Finer S, Lindgren CM, Wilson GA, Rakyan VK, et al. (2010) Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus. PLoS ONE 5(11): e14040. doi:10.1371/journal.pone.0014040
Engreitz JM, Agarwala V, Mirny LA (2012) Three-Dimensional Genome Architecture Influences Partner Selection for Chromosomal Translocations in Human Disease. PLoS ONE 7(9): e44196. doi:10.1371/journal.pone.0044196
Jones L, Holmans PA, Hamshere ML, Harold D, Moskvina V, et al. (2010) Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer’s Disease. PLoS ONE 5(11): e13950. doi:10.1371/journal.pone.0013950
Jun G, Moncaster JA, Koutras C, Seshadri S, Buros J, et al. (2012) δ-Catenin Is Genetically and Biologically Associated with Cortical Cataract and Future Alzheimer-Related Structural and Functional Brain Changes. PLoS ONE 7(9): e43728. doi:10.1371/journal.pone.0043728
Kirin M, McQuillan R, Franklin CS, Campbell H, McKeigue PM, et al. (2010) Genomic Runs of Homozygosity Record Population History and Consanguinity. PLoS ONE 5(11): e13996. doi:10.1371/journal.pone.0013996
Nakano M, Ikeda Y, Tokuda Y, Fuwa M, Omi N, et al. (2012) Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese. PLoS ONE 7(3): e33389. doi:10.1371/journal.pone.0033389
Valsesia A, Rimoldi D, Martinet D, Ibberson M, Benaglio P, et al. (2011) Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma. PLoS ONE 6(4): e18369. doi:10.1371/journal.pone.0018369
Zhang D, Qian Y, Akula N, Alliey-Rodriguez N, Tang J, et al. (2011) Accuracy of CNV Detection from GWAS Data. PLoS ONE 6(1): e14511. doi:10.1371/journal.pone.0014511