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Including Genetic Variables in NTCP Models Where Are We? Where Are We Going?
Published in Tiziana Rancati, Claudio Fiorino, Modelling Radiotherapy Side Effects, 2019
Sarah L. Kerns, Suhong Yu, Catharine M. L. West
Variation in the human genome can take several different forms including single nucleotide polymorphisms (SNPs), rare variants, small insertions and deletions (indels), copy number variants (CNVs) and epigenetic modifications. Each class of variants can affect disease risk and response to environmental exposures such as therapeutic radiation. Our knowledge of the number and type of genetic variations across the human genome has increased dramatically since the completion of the Human Genome Project in 2003 (Lander 2001), followed by genome-wide SNP genotyping and deep sequencing initiatives including the International HapMap Project in 2005 (International HapMap 2005) and the 1000 Genomes Project in 2015 (Genomes Project et al. 2015). These initiatives have greatly increased our knowledge of the architecture of the human genome and enabled rapid advances in our understanding of the genetic basis for complex diseases and traits. They have also led to technological advances in software for processing large genomic datasets and extracting meaningful information from an otherwise overwhelming set of data. In the context of radiogenomics research, much of the focus to date has been on SNPs and rare variants, though there is growing interest in CNVs and epigenetic changes.
Precision medicine for colorectal cancer
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Candan Hızel, Şükrü Tüzmen, Arsalan Amirfallah, Gizem Çalıbaşı Koçal, Duygu Abbasoğlu, Haluk Onat, Yeşim Yıldırım, Yasemin Baskın
Since the completion of both the Human Genome Project (HGP) (Venter et al., 2001) and the International HapMap project (Frazer et al., 2007), recent progress in genotyping technology has facilitated the use of GWAS as a “gene-hunting study” for linking specific genetic variants with human disease by many thousand loci simultaneously (Hindorff et al., 2009; Visscher et al., 2017).
Genetics of diabetic pregnancy
Published in Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer, Textbook of Diabetes and Pregnancy, 2018
Completed in 2003, the Human Genome Project produced a high-quality sequence of the human genome and provided details regarding its structure and organization. This was followed by the International HapMap Project in 2005, which provided a catalog of common genetic variants in human beings and how they are distributed among diverse populations.34 Both these important initiatives, along with advances in molecular technologies such as arrays and next-generation sequencing, provided the foundation for investigators to be able to evaluate many genes at one time and begin to make meaning of changes found in genotypes of many different individuals and populations. See further Table 9.4.
Unbounding ELSI: The Ongoing Work of Centering Equity and Justice
Published in The American Journal of Bioethics, 2023
Chessa Adsit-Morris, Rayheann NaDejda Collins, Sara Goering, James Karabin, Sandra Soo-Jin Lee, Jenny Reardon
The articles in this volume help with this by casting a critical eye on some of ELSI’s most celebrated innovations and techniques—for example, community and public engagement efforts. Ever since the development of the International HapMap Project (HapMap) over two decades ago, community engagement has been a key ethical intervention used by genome scientists to reduce the chances of discrimination while also increasing the diversity of genomic data populations. Leaders of the HapMap—which was a worldwide effort to map human genetic variation—were keenly aware of the controversies sparked by the Human Genome Diversity Project (HGDP), an initiative that aimed to archive human genetic diversity by collecting the genomes of “isolated indigenous populations” (Reardon 2017). To distance themselves from the HGDP, HapMap leaders emphasized that they would sample “large populations” who held majority status in society and establish a robust community engagement program (NHGRI 2002). At the time, HapMap community engagements represented the largest investment of ELSI funds and deployment of ELSI researchers ever seen in genomics. However, they enacted an all too bounded approach to ethics that failed to understand the deeper questions of power and knowledge raised by both the HGDP and the HapMap: How should human groups be constituted and for what ends?
Germline genetic variations in methotrexate pathway are associated with pharmacokinetics, outcome, and toxicity in patients with primary central nervous system lymphoma
Published in Expert Review of Clinical Pharmacology, 2023
Zhuo Wu, Ziran Li, Xiaoyan Qiu, Mingkang Zhong, Tianling Ding
Variants in genes related to the intracellular and efflux transport of MTX, namely SLCO1B1, SLC19A1, ABCC2, and ABCB1, were selected based on the strength of evidence from published association studies [13,25–28]. For variants involved in other genes of the MTX pathway (MTX polyglutamate formation: FPGS and GGH; folate cycle and DNA synthesis: DHFR, TYMS, ATIC, MTHFR, MTRR, and MTR), we extracted the list of SNPs corresponding to the Han population of Beijing, China (CHB) from the international HapMap project database (www.hapmap.org). First, we selected SNPs with a reported minor allele frequency > 0.1, and then selected tag SNPs by pairwise tagging (r2 > 0.8). Overall, 35 SNPs were chosen as tag SNPs to cover the eight genes of interest. Genomic DNA was isolated using a TIANamp Blood DNA Kit (Tiangen Biotech, Beijing, China), according to the manufacturer’s instructions. All SNPs were determined using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry by independent external contractors (Benegene Biotechnologies Co. Ltd., Shanghai, China). Further details can be found in our previous study [29].
No association between the vitamin D pathway gene polymorphisms and bone biomarkers response to calcium and low dose calcitriol supplementation in postmenopausal Chinese women: a one-year prospective study
Published in Biomarkers, 2018
Jiemei Gu, Chun Wang, Hao Zhang, Hua Yue, Weiwei Hu, Jinwei He, Wenzhen Fu, Zhenlin Zhang
Fifteen candidate genes were selected according to the following criteria: (1) evidence of a significant association in previous GWASs; and (2) biological importance in vitamin D metabolism, transportation, or degradation. The selected key genes were ACADSB, CUBN, CYP1A1, CYP2C9, CYP2J2, CYP2R1, CYP3A4, CYP11A1, CYP24A1, CYP27A1, CYP27B1, DHCR7, GC, NADSYN1 and PTH (Zhang et al. 2013). The basic characteristics of these 15 genes are shown in Table 1. The detailed functions of the candidate genes are described in our former study (Zhang et al. 2013). For the studied genes, tagging SNPs were selected from the International HapMap Project (http://www.hapmap.org/cgi-perl/gbrowse/hapmap3_B36). The SNPs were selected according to the following criteria: (1) validation status, especially in Chinese; (2) degree of heterozygosity (minor allele frequencies [MAFs] > 0.1); (3) binned by the algorithm such that the pairwise linkage disequilibrium (LD) exceeds a threshold r2 (r2 ¼ 0.05); and (4) requirement for tag-SNPs. Potentially functional SNPs in candidate genes or SNPs reported in GWASs were forced into the SNP selection process.