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    Polymorphism discovery in 51 chemotherapy pathway genes.
    Hum Mol Genet 2005 Dec 20;14(23):3595-603. Epub 2005 Oct 20.
    Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
    Candidate gene pharmacogenetic studies offer a strategy for the rapid assessment of putative predictive markers. As a first step toward studying the pharmacogenetics of cancer chemotherapy, 51 candidate genes from the pathways of antineoplastic agents were resequenced to identify common genetic polymorphisms that might alter therapeutic response or toxicity. Forty DNA samples were screened from each of three population groups: African-Americans, Asian-Americans and European-Americans. Nearly 378 kb of genomic sequence was obtained from each sample. Nine hundred and four variants were identified, including 139 coding single nucleotide polymorphisms (cSNPs). Three hundred and fifty-six (40%) polymorphisms were common to all three populations and 366 (41%) were population specific. Three hundred and forty-six (38%) variants were novel polymorphisms that were not present in the three public databases that were examined. One hundred and eleven (35%) of the 319 non-synonymous cSNPs that were identified by either resequencing or database mining were predicted by PolyPhen to be either possibly or probably damaging. For the non-synonymous cSNPs identified by resequencing, both the number of cSNPs found and the maximum estimated allele frequency decreased with increasing predicted severity. These results provide experimental validation and estimated allele frequencies for polymorphisms in three common ethnic groups and facilitate applied pharmacogenetic studies of anticancer drugs.

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    Human sulfotransferase SULT1C1 pharmacogenetics: gene resequencing and functional genomic studies.
    Pharmacogenetics 2001 Dec;11(9):747-56
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School-Mayo Medical School-Mayo Clinic, Rochester MN, USA.
    Sulfotransferase (SULT) enzymes catalyze an important phase II reaction in the biotransformation of many drugs and other xenobiotics. We previously cloned the human SULT1C1 cDNA and gene as steps toward pharmacogenetic studies. We have now 'resequenced' the exons, portions of introns flanking exons and approximately 315 bp of the 5' flanking region of SULT1C1 in 89 DNA samples from Caucasian subjects to identify common genetic polymorphisms. Read More
    Human methylenetetrahydrofolate reductase pharmacogenomics: gene resequencing and functional genomics.
    Pharmacogenet Genomics 2006 Apr;16(4):265-77
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
    5,10-Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in the folate metabolic pathway. Common genetic polymorphisms in the human MTHFR gene are associated with individual variation in the efficacy and toxicity of chemotherapeutic agents, such as methotrexate and 5-fluorouracil. However, the full range of polymorphisms and intragene haplotypes in the human MTHFR gene remains unclear. Read More
    Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research.
    BMC Genet 2007 Oct 17;8:71. Epub 2007 Oct 17.
    Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA.
    Background: GABA transporter-1 (GAT-1; genetic locus SLC6A1) is emerging as a novel target for treatment of neuropsychiatric disorders. To understand how population differences might influence strategies for pharmacogenetic studies, we identified patterns of genetic variation and linkage disequilibrium (LD) in SLC6A1 in five populations representing three continental groups.

    Results: We resequenced 12. Read More
    Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype.
    BMC Med Genet 2007 Nov 26;8:70. Epub 2007 Nov 26.
    Center for Genome Science, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul 122-701, Republic of Korea.
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