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A signature of balancing selection in the region upstream to the human UGT2B4 gene and implications for breast cancer risk

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Abstract

UDP-glucuronosyltransferase 2 family, polypeptide B4 (UGT2B4) is an important metabolizing enzyme involved in the clearance of many xenobiotics and endogenous substrates, especially steroid hormones and bile acids. The HapMap data show that numerous SNPs upstream of UGT2B4 are in near-perfect linkage disequilibrium with each other and occur at intermediate frequency, indicating that this region might contain a target of natural selection. To investigate this possibility, we chose three regions (4.8 kb in total) for resequencing and observed a striking excess of intermediate-frequency alleles that define two major haplotypes separated by many mutation events and with little differentiation across populations, thus suggesting that the variation pattern upstream UGT2B4 is highly unusual and may be the result of balancing selection. We propose that this pattern is due to the maintenance of a regulatory polymorphism involved in the fine tuning of UGT2B4 expression so that heterozygous genotypes result in optimal enzyme levels. Considering the important role of steroid hormones in breast cancer susceptibility, we hypothesized that variation in this region could predispose to breast cancer. To test this hypothesis, we genotyped tag SNP rs13129471 in 1,261 patients and 825 normal women of African ancestry from three populations. The frequency comparison indicated that rs13129471 was significantly associated with breast cancer after adjusting for ethnicity [P = 0.003; heterozygous odds ratio (OR) 1.02, 95% confidence interval (CI) 0.81–1.28; homozygous OR 1.50, 95% CI 1.15–1.95]. Our results provide new insights into UGT2B4 sequence variation and indicate that a signal of natural selection may lead to the identification of disease susceptibility variants.

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References

  • Akey JM, Zhang G, Zhang K, Jin L, Shriver MD (2002) Interrogating a high-density SNP map for signatures of natural selection. Genome Res 12:1805–1814. doi:10.1101/gr.631202

    Article  PubMed  CAS  Google Scholar 

  • Allerston CK, Shimizu M, Fujieda M, Shephard EA, Yamazaki H, Phillips IR (2007) Molecular evolution and balancing selection in the flavin-containing monooxygenase 3 gene (FMO3). Pharmacogenet Genomics 17:827–839. doi:10.1097/FPC.0b013e328256b198

    Article  PubMed  CAS  Google Scholar 

  • Andres AM, Hubisz MJ, Indap A, Torgerson DG, Degenhardt JD, Boyko AR, Gutenkunst RN, White TJ, Green ED, Bustamante CD, Clark AG, Nielsen R (2009) Targets of balancing selection in the human genome. Mol Biol Evol 26:2755–2764. doi:10.1093/molbev/msp190

    Article  PubMed  CAS  Google Scholar 

  • Andres AM, Dennis MY, Kretzschmar WW, Cannons JL, Lee-Lin S-Q, Hurle B, Schwartzberg PL, Williamson SH, Bustamante CD, Nielsen R, Clark AG, Green ED (2010) Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation. PLoS Genet 6:e1001157. doi:10.1371/journal.pgen.1001157

    Article  PubMed  Google Scholar 

  • Bamshad MJ, Mummidi S, Gonzalez E, Ahuja SS, Dunn DM, Watkins WS, Wooding S, Stone AC, Jorde LB, Weiss RB, Ahuja SK (2002) A strong signature of balancing selection in the 5′ cis-regulatory region of CCR5. Proc Natl Acad Sci USA 99:10539–10544. doi:10.1073/pnas.162046399

    Article  PubMed  CAS  Google Scholar 

  • Bandelt HJ, Forster P, Rohl A (1999) Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol 16:37–48

    PubMed  CAS  Google Scholar 

  • Barbier O, Duran-Sandoval D, Pineda-Torra I, Kosykh V, Fruchart JC, Staels B (2003a) Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme. J Biol Chem 278:32852–32860. doi:10.1074/jbc.M305361200

    Article  PubMed  CAS  Google Scholar 

  • Barbier O, Torra IP, Sirvent A, Claudel T, Blanquart C, Duran-Sandoval D, Kuipers F, Kosykh V, Fruchart JC, Staels B (2003b) FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity. Gastroenterology 124:1926–1940. doi:10.1016/S0016-5085(03)00388-3

    Article  PubMed  CAS  Google Scholar 

  • Belanger A, Pelletier G, Labrie F, Barbier O, Chouinard S (2003) Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metab 14:473–479. doi:10.1016/j.tem.2003.10.005

    Article  PubMed  CAS  Google Scholar 

  • Biswas S, Akey JM (2006) Genomic insights into positive selection. Trends Genet 22:437–446. doi:10.1016/j.tig.2006.06.005

    Article  PubMed  CAS  Google Scholar 

  • Black FL, Hedrick PW (1997) Strong balancing selection at HLA loci: evidence from segregation in South Amerindian families. Proc Natl Acad Sci USA 94:12452–12456

    Article  PubMed  CAS  Google Scholar 

  • Bubb KL, Bovee D, Buckley D, Haugen E, Kibukawa M, Paddock M, Palmieri A, Subramanian S, Zhou Y, Kaul R, Green P, Olson MV (2006) Scan of human genome reveals no new Loci under ancient balancing selection. Genetics 173:2165–2177. doi:10.1534/genetics.106.055715

    Article  PubMed  CAS  Google Scholar 

  • Cagliani R, Fumagalli M, Riva S, Pozzoli U, Comi GP, Menozzi G, Bresolin N, Sironi M (2008) The signature of long-standing balancing selection at the human defensin beta-1 promoter. Genome Biol 9:R143. doi:10.1186/gb-2008-9-9-r143

    Article  PubMed  Google Scholar 

  • Cagliani R, Fumagalli M, Riva S, Pozzoli U, Comi GP, Bresolin N, Sironi M (2010a) Genetic variability in the ACE gene region surrounding the Alu I/D polymorphism is maintained by balancing selection in human populations. Pharmacogenet Genomics 20:131–134. doi:10.1097/FPC.0b013e3283333532

    Article  PubMed  CAS  Google Scholar 

  • Cagliani R, Riva S, Biasin M, Fumagalli M, Pozzoli U, Lo Caputo S, Mazzotta F, Piacentini L, Bresolin N, Clerici M, Sironi M (2010b) Genetic diversity at endoplasmic reticulum aminopeptidases is maintained by balancing selection and is associated with natural resistance to HIV-1 infection. Hum Mol Genet 19:4705–4714. doi:10.1093/hmg/ddq401

    Article  PubMed  CAS  Google Scholar 

  • Carlson CS, Eberle MA, Rieder MJ, Yi Q, Kruglyak L, Nickerson DA (2004) Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 74:106–120. doi:10.1086/381000

    Article  PubMed  CAS  Google Scholar 

  • Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR (1999) Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer Study of Osteoporotic Fractures Research Group. Ann Intern Med 130:270–277

    PubMed  CAS  Google Scholar 

  • Cavalli-Sforza LL, Feldman MW (2003) The application of molecular genetic approaches to the study of human evolution. Nat Genet 33 Suppl: 266-275. doi: 10.1038/ng1113

  • Charlesworth D (2006) Balancing selection and its effects on sequences in nearby genome regions. PLoS Genet 2:e64. doi:10.1371/journal.pgen.0020064

    Article  PubMed  Google Scholar 

  • Currat M, Trabuchet G, Rees D, Perrin P, Harding RM, Clegg JB, Langaney A, Excoffier L (2002) Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta(S) Senegal mutation. Am J Hum Genet 70:207–223. doi:10.1086/338304

    Article  PubMed  CAS  Google Scholar 

  • Desai AA, Innocenti F, Ratain MJ (2003) UGT pharmacogenomics: implications for cancer risk and cancer therapeutics. Pharmacogenetics 13:517–523. doi:10.1097/01.fpc.0000054116.14659.e5

    Article  PubMed  CAS  Google Scholar 

  • Fu YX (1997) Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics 147:915–925

    PubMed  CAS  Google Scholar 

  • Fu YX, Li WH (1993) Statistical tests of neutrality of mutations. Genetics 133:693–709

    PubMed  CAS  Google Scholar 

  • Fumagalli M, Cagliani R, Pozzoli U, Riva S, Comi GP, Menozzi G, Bresolin N, Sironi M (2009a) A population genetics study of the familial Mediterranean fever gene: evidence of balancing selection under an overdominance regime. Genes Immun 10:678–686. doi:10.1038/gene.2009.59

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli M, Cagliani R, Pozzoli U, Riva S, Comi GP, Menozzi G, Bresolin N, Sironi M (2009b) Widespread balancing selection and pathogen-driven selection at blood group antigen genes. Genome Res 19:199–212. doi:10.1101/gr.082768.108

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, Bresolin N, Sironi M (2009c) Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J Exp Med 206:1395–1408. doi:10.1084/jem.20082779

    Article  PubMed  CAS  Google Scholar 

  • Gardner-Stephen DA, Mackenzie PI (2008) Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression. Curr Drug Metab 9:439–452

    Article  PubMed  CAS  Google Scholar 

  • Grigorova M, Rull K, Laan M (2007) Haplotype structure of FSHB, the beta-subunit gene for fertility-associated follicle-stimulating hormone: possible influence of balancing selection. Ann Hum Genet 71:18–28. doi:10.1111/j.1469-1809.2006.00299.x

    Article  PubMed  CAS  Google Scholar 

  • Guillemette C (2003) Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J 3:136–158. doi:10.1038/sj.tpj.6500171

    Article  PubMed  CAS  Google Scholar 

  • Guillemette C, Belanger A, Lepine J (2004) Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview. Breast Cancer Res 6:246–254. doi:10.1186/bcr936

    Article  PubMed  CAS  Google Scholar 

  • Hirayasu K, Ohashi J, Kashiwase K, Takanashi M, Satake M, Tokunaga K, Yabe T (2006) Long-term persistence of both functional and non-functional alleles at the leukocyte immunoglobulin-like receptor A3 (LILRA3) locus suggests balancing selection. Hum Genet 119:436–443. doi:10.1007/s00439-006-0152-y

    Article  PubMed  CAS  Google Scholar 

  • Hollox EJ, Armour JA (2008) Directional and balancing selection in human beta-defensins. BMC Evol Biol 8:113. doi:10.1186/1471-2148-8-113

    Article  PubMed  Google Scholar 

  • Hudson RR (2002) Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinformatics 18:337–338. doi:10.1093/bioinformatics/18.2.337

    Article  PubMed  CAS  Google Scholar 

  • Izukawa T, Nakajima M, Fujiwara R, Yamanaka H, Fukami T, Takamiya M, Aoki Y, Ikushiro S, Sakaki T, Yokoi T (2009) Quantitative analysis of UDP-glucuronosyltransferase (UGT) 1A and UGT2B expression levels in human livers. Drug Metab Dispos 37:1759–1768. doi:10.1124/dmd.109.027227

    Article  PubMed  CAS  Google Scholar 

  • Jakobsson J, Ekstrom L, Inotsume N, Garle M, Lorentzon M, Ohlsson C, Roh HK, Carlstrom K, Rane A (2006) Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. J Clin Endocrinol Metab 91:687–693. doi:10.1210/jc.2005-1643

    Article  PubMed  CAS  Google Scholar 

  • Juul A, Sorensen K, Aksglaede L, Garn I, Rajpert-De Meyts E, Hullstein I, Hemmersbach P, Ottesen AM (2009) A common deletion in the uridine diphosphate glucuronyltransferase (UGT) 2B17 gene is a strong determinant of androgen excretion in healthy pubertal boys. J Clin Endocrinol Metab 94:1005–1011. doi:10.1210/jc.2008-1984

    Article  PubMed  CAS  Google Scholar 

  • Key TJ (1999) Serum oestradiol and breast cancer risk. Endocr Relat Cancer 6:175–180

    Article  PubMed  CAS  Google Scholar 

  • King CD, Rios GR, Green MD, Tephly TR (2000) UDP-glucuronosyltransferases. Curr Drug Metab 1:143–161

    Article  PubMed  CAS  Google Scholar 

  • Librado P, Rozas J (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25:1451–1452. doi:10.1093/bioinformatics/btp187

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Fu Y, Liu Z, Lin B, Xie Y, Liu Y, Xu Y, Lin J, Fan X, Dong M, Zeng K, Wu CI, Xu A (2006) An ancient balanced polymorphism in a regulatory region of human major histocompatibility complex is retained in Chinese minorities but lost worldwide. Am J Hum Genet 78:393–400. doi:10.1086/500593

    Article  PubMed  CAS  Google Scholar 

  • Mackenzie PI, Bock KW, Burchell B, Guillemette C, Ikushiro S, Iyanagi T, Miners JO, Owens IS, Nebert DW (2005) Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics 15:677–685

    Article  PubMed  CAS  Google Scholar 

  • Nagar S, Remmel RP (2006) Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer. Oncogene 25:1659–1672. doi:10.1038/sj.onc.1209375

    Article  PubMed  CAS  Google Scholar 

  • Nakamura A, Nakajima M, Yamanaka H, Fujiwara R, Yokoi T (2008) Expression of UGT1A and UGT2B mRNA in human normal tissues and various cell lines. Drug Metab Dispos 36:1461–1464. doi:10.1124/dmd.108.021428

    Article  PubMed  CAS  Google Scholar 

  • Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG (2007) Recent and ongoing selection in the human genome. Nat Rev Genet 8:857–868. doi:10.1038/nrg2187

    Article  PubMed  CAS  Google Scholar 

  • Norman P, Cook M, Carey BS, Carrington CF, Verity D, Hameed K, Ramdath DD, Chandanayingyong D, Leppert M, Stephens HF, Vaughan RW (2004) SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex. Immunogenetics 56. doi:10.1007/s00251-004-0674-1

  • Ohno S, Nakajin S (2009) Determination of mRNA expression of human UDP-glucuronosyltransferases and application for localization in various human tissues by real-time reverse transcriptase-polymerase chain reaction. Drug Metab Dispos 37:32–40. doi:10.1124/dmd.108.023598

    Article  PubMed  CAS  Google Scholar 

  • Paul W, John BD (2007) Introduction to endocrinology. In: Gardner DG, Shoback D (eds) Greenspan’s basic and clinical endocrinology, 8th edn. The McGraw-Hill Companies, New York, pp 1–34

    Google Scholar 

  • Reich DE, Schaffner SF, Daly MJ, McVean G, Mullikin JC, Higgins JM, Richter DJ, Lander ES, Altshuler D (2002) Human genome sequence variation and the influence of gene history, mutation and recombination. Nat Genet 32:135–142. doi:10.1038/ng947

    Article  PubMed  CAS  Google Scholar 

  • Sabeti PC, Reich DE, Higgins JM, Levine HZ, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler D, Cooper R, Kwiatkowski D, Ward R, Lander ES (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419:832–837. doi:10.1038/nature01140

    Article  PubMed  CAS  Google Scholar 

  • Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, Hunt SE, Cole CG, Coggill PC, Rice CM, Ning Z, Rogers J, Bentley DR, Kwok PY, Mardis ER, Yeh RT, Schultz B, Cook L, Davenport R, Dante M, Fulton L, Hillier L, Waterston RH, McPherson JD, Gilman B, Schaffner S, Van Etten WJ, Reich D, Higgins J, Daly MJ, Blumenstiel B, Baldwin J, Stange-Thomann N, Zody MC, Linton L, Lander ES, Altshuler D (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–933. doi:10.1038/35057149

    Google Scholar 

  • Soejima M, Tachida H, Tsuneoka M, Takenaka O, Kimura H, Koda Y (2005) Nucleotide sequence analyses of human complement 6 (C6) gene suggest balancing selection. Ann Hum Genet 69:239–252. doi:10.1046/j.1529-8817.2005.00165.x

    Article  PubMed  CAS  Google Scholar 

  • Sparks R, Ulrich CM, Bigler J, Tworoger SS, Yasui Y, Rajan KB, Porter P, Stanczyk FZ, Ballard-Barbash R, Yuan X, Lin MG, McVarish L, Aiello EJ, McTiernan A (2004) UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients. Breast Cancer Res 6:R488–R498. doi:10.1186/bcr818

    Article  PubMed  CAS  Google Scholar 

  • Stephens M, Donnelly P (2003) A comparison of bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 73:1162–1169. doi:10.1086/379378

    Article  PubMed  CAS  Google Scholar 

  • Stephens M, Sloan JS, Robertson PD, Scheet P, Nickerson DA (2006) Automating sequence-based detection and genotyping of SNPs from diploid samples. Nat Genet 38:375–381. doi:10.1038/ng1746

    Article  PubMed  CAS  Google Scholar 

  • Tajima F (1983) Evolutionary relationship of DNA sequences in finite populations. Genetics 105:437–460

    PubMed  CAS  Google Scholar 

  • Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595

    PubMed  CAS  Google Scholar 

  • Tan Z, Shon AM, Ober C (2005) Evidence of balancing selection at the HLA-G promoter region. Hum Mol Genet 14:3619–3628. doi:10.1093/hmg/ddi389

    Article  PubMed  CAS  Google Scholar 

  • The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449:851–861. doi:10.1038/nature06258

    Google Scholar 

  • Thijssen JH, Blankenstein MA (1989) Endogenous oestrogens and androgens in normal and malignant endometrial and mammary tissues. Eur J Cancer Clin Oncol 25:1953–1959

    Article  PubMed  CAS  Google Scholar 

  • Thomas HV, Reeves GK, Key TJ (1997) Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8:922–928

    Article  PubMed  CAS  Google Scholar 

  • Tukey RH, Strassburg CP (2000) Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581–616. doi:10.1146/annurev.pharmtox.40.1.581

    Article  PubMed  CAS  Google Scholar 

  • Verrelli BC, McDonald JH, Argyropoulos G, Destro-Bisol G, Froment A, Drousiotou A, Lefranc G, Helal AN, Loiselet J, Tishkoff SA (2002) Evidence for balancing selection from nucleotide sequence analyses of human G6PD. Am J Hum Genet 71:1112–1128. doi:10.1086/344345

    Article  PubMed  CAS  Google Scholar 

  • Voight BF, Adams AM, Frisse LA, Qian Y, Hudson RR, Di Rienzo A (2005) Interrogating multiple aspects of variation in a full resequencing data set to infer human population size changes. Proc Natl Acad Sci USA 102:18508–18513. doi:10.1073/pnas.0507325102

    Article  PubMed  CAS  Google Scholar 

  • Voight BF, Kudaravalli S, Wen X, Pritchard JK (2006) A map of recent positive selection in the human genome. PLoS Biol 4:e72. doi:10.1371/journal.pbio.0040072

    Article  PubMed  Google Scholar 

  • Wang ET, Kodama G, Baldi P, Moyzis RK (2006) Global landscape of recent inferred Darwinian selection for Homo sapiens. Proc Nat Acad Sci 103:135–140. doi:10.1073/pnas.0509691102

    Article  PubMed  CAS  Google Scholar 

  • Watterson GA (1975) On the number of segregating sites in genetical models without recombination. Theor Popul Biol 7:256–276

    Article  PubMed  CAS  Google Scholar 

  • Weir BS, Cockerham CC (1984) Estimating F-statistics for the analysis of population structure. Evolution 38:1358–1370

    Article  Google Scholar 

  • White PC (1994) Disorders of aldosterone biosynthesis and action. N Engl J Med 331:250–258

    Article  PubMed  CAS  Google Scholar 

  • Wooding S, Kim UK, Bamshad MJ, Larsen J, Jorde LB, Drayna D (2004) Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am J Hum Genet 74:637–646. doi:10.1086/383092

    Article  PubMed  CAS  Google Scholar 

  • Wright S (1950) Genetical structure of populations. Nature 166:247–249

    Article  PubMed  CAS  Google Scholar 

  • Xue Y, Sun D, Daly A, Yang F, Zhou X, Zhao M, Huang N, Zerjal T, Lee C, Carter NP, Hurles ME, Tyler-Smith C (2008) Adaptive evolution of UGT2B17 copy-number variation. Am J Hum Genet 83:337–346. doi:10.1016/j.ajhg.2008.08.004

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Zhang J, Xie W (2005) Xenobiotic nuclear receptor-mediated regulation of UDP-glucuronosyl-transferases. Curr Drug Metab 6:289–298

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Prof. Yoav Gilad and Dr. Jin-Xian Liu (University of California at Irvine) for providing chimpanzees genomic DNA and technical advice, respectively. We also thank the anonymous reviewers for their helpful comments. This research was supported by National Institutes of Health (CA125183 and U01 GM61393 to A.D.R.).

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Authors and Affiliations

  1. Department of Human Genetics, University of Chicago, 920 E. 58th Street, Chicago, IL, 60637, USA

    Chang Sun, Catherine Southard, David B. Witonsky & Anna Di Rienzo

  2. Department of Health Studies, University of Chicago, Chicago, IL, 60637, USA

    Dezheng Huo

  3. Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA

    Barbara Nemesure, M. Cristina Leske & Suh-Yuh Wu

  4. Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados

    Anselm Hennis

  5. Department of Medicine, University of Chicago, Chicago, IL, 60637, USA

    Olufunmilayo I. Olopade

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  1. Chang Sun
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Correspondence to Anna Di Rienzo.

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Sun, C., Huo, D., Southard, C. et al. A signature of balancing selection in the region upstream to the human UGT2B4 gene and implications for breast cancer risk. Hum Genet 130, 767–775 (2011). https://doi.org/10.1007/s00439-011-1025-6

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