Skip to main content
SpringerLink
Log in
Book cover

Applied Computational Genomics pp 61–82Cite as

QTL Mapping of Molecular Traits for Studies of Human Complex Diseases

  • Chapter
  • First Online:

Part of the book series: Translational Bioinformatics ((TRBIO,volume 1))

Abstract

Genetic mapping of quantitative trait loci (QTL) offers a powerful and efficient approach to discover putative regulatory regions of traits and to define novel functional implications of genetic variants. Here we reviewed recent progress on QTL mapping of molecular traits, including gene expression, DNA methylation, as well as protein expression, metabolites. QTL mapping of molecular traits has better chance to succeed in relatively small sample size study as fewer nongenetic factors or gene-gene interactions may involve. Knowledge derived from QTL mapping will help us to uncover understanding of biology in complex traits and diseases and enhance power of genetic association study. In the context of study of complex diseases, we focused on expression QTL and methylation QTL, presenting major findings and technique considerations, including experimental platform, sample quality, size, and heterogeneity, as well as analytical procedure and significance criteria. Lastly, we discussed the current and future use of QTL data in study of complex diseases.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Alberts R, Terpstra P, Li Y, Breitling R, Nap JP, Jansen RC. Sequence polymorphisms cause many false cis eQTLs. PLoS One. 2007;2(7):e622.

    Article  PubMed  Google Scholar 

  • Ball MP, Li JB, Gao Y, Lee JH, LeProust EM, Park IH, Xie B, Daley GQ, Church GM. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27(4):361–8.

    Article  PubMed  CAS  Google Scholar 

  • Baum AE, et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry. 2008;13(2):197–207.

    Article  PubMed  CAS  Google Scholar 

  • Bell JT, Pai AA, Pickrell JK, Gaffney DJ, Pique-Regi R, Degner JF, Gilad Y, Pritchard JK. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol. 2011;12(1):R10.

    Article  PubMed  CAS  Google Scholar 

  • Breen G, et al. Replication of association of 3p21.1 with susceptibility to bipolar disorder but not major depression. Nat Genet. 2011;43(1):3–5.

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Grennan K, Badner J, Zhang D, Gershon E, Jin L, Liu C. Removing batch effects in analysis of expression microarray data: an evaluation of six batch adjustment methods. PLoS One. 2011a;6(2):e17238.

    Article  PubMed  CAS  Google Scholar 

  • Chen YA, Choufani S, Ferreira JC, Grafodatskaya D, Butcher DT, Weksberg R. Sequence overlap between autosomal and sex-linked probes on the Illumina HumanMethylation27 microarray CHEN2011. Genomics. 2011b;97(4):214–22.

    Article  PubMed  CAS  Google Scholar 

  • Cheung VG, Spielman RS. Genetics of human gene expression: mapping DNA variants that influence gene expression. Nat Rev Genet. 2009;10(9):595–604.

    Article  PubMed  CAS  Google Scholar 

  • Cheung VG, Spielman RS, Ewens KG, Weber TM, Morley M, Burdick JT. Mapping determinants of human gene expression by regional and genome-wide association. Nature. 2005;437(7063):1365–9.

    Article  PubMed  CAS  Google Scholar 

  • Cichon S, et al. Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. Am J Hum Genet. 2011;88(3):372–81.

    Article  PubMed  CAS  Google Scholar 

  • Clark TA, Schweitzer AC, Chen TX, Staples MK, Lu G, Wang H, Williams A, Blume JE. Discovery of tissue-specific exons using comprehensive human exon microarrays. Genome Biol. 2007;8(4):R64.

    Article  PubMed  Google Scholar 

  • Colantuoni C, et al. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature. 2011;478(7370):519–23.

    Article  PubMed  CAS  Google Scholar 

  • Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M. Mapping complex disease traits with global gene expression. Nat Rev Genet. 2009;10(3):184–94.

    Article  PubMed  CAS  Google Scholar 

  • Damerval C, Maurice A, Josse JM, de Vienne D. Quantitative trait loci underlying gene product variation: a novel perspective for analyzing regulation of genome expression. Genetics. 1994;137(1):289–301.

    PubMed  CAS  Google Scholar 

  • Deng J, et al. Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol. 2009;27(4):353–60.

    Article  PubMed  CAS  Google Scholar 

  • Dimas AS, et al. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science. 2009;325(5945):1246–50.

    Article  PubMed  CAS  Google Scholar 

  • Dixon AL, et al. A genome-wide association study of global gene expression. Nat Genet. 2007;39(10):1202–7.

    Article  PubMed  CAS  Google Scholar 

  • Dobrin R, Greenawalt DM, Hu G, Kemp DM, Kaplan LM, Schadt EE, Emilsson V. Dissecting cis regulation of gene expression in human metabolic tissues. PLoS One. 2011;6(8):e23480.

    Article  PubMed  CAS  Google Scholar 

  • Duan S, Zhang W, Bleibel WK, Cox NJ, Dolan ME. SNPinProbe_1.0: a database for filtering out probes in the Affymetrix GeneChip human exon 1.0 ST array potentially affected by SNPs. Bioinformation. 2008;2(10):469–70.

    Article  PubMed  Google Scholar 

  • Eichler EE, Flint J, Gibson G, Kong A, Leal SM, Moore JH, Nadeau JH. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010;11(6):446–50.

    Article  PubMed  CAS  Google Scholar 

  • Emilsson V, et al. Genetics of gene expression and its effect on disease. Nature. 2008;452(7186):423–8.

    Article  PubMed  CAS  Google Scholar 

  • Fehrmann RS, et al. Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet. 2011;7(8):e1002197.

    Article  PubMed  CAS  Google Scholar 

  • Ferreira MA, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. 2008;40(9):1056–8.

    Article  PubMed  CAS  Google Scholar 

  • Fransen K, et al. Analysis of SNPs with an effect on gene expression identifies UBE2L3 and BCL3 as potential new risk genes for Crohn’s disease. Hum Mol Genet. 2010;19(17):3482–8.

    Article  PubMed  CAS  Google Scholar 

  • Gamazon ER, Zhang W, Dolan ME, Cox NJ. Comprehensive survey of SNPs in the Affymetrix exon array using the 1000 Genomes dataset. PLoS One. 2010;5(2):e9366.

    Article  PubMed  Google Scholar 

  • Gamazon ER, et al. Enrichment of cis-regulatory gene expression SNPs and methylation quantitative trait loci among bipolar disorder susceptibility variants GAMAZON2012. Mol Psychiatry. 2012.

    Google Scholar 

  • Gibbs JR, et al. Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genet. 2010;6(5):e1000952.

    Article  PubMed  Google Scholar 

  • Gieger C, et al. Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum. PLoS Genet. 2008;4(11):e1000282.

    Article  PubMed  Google Scholar 

  • Heap GA, et al. Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing. Hum Mol Genet. 2010;19(1):122–34.

    Article  PubMed  CAS  Google Scholar 

  • Heinzen EL, et al. Tissue-specific genetic control of splicing: implications for the study of complex traits. PLoS Biol. 2008;6(12):e1.

    Article  PubMed  Google Scholar 

  • Hicks AA, et al. Genetic determinants of circulating sphingolipid concentrations in European populations. PLoS Genet. 2009;5(10):e1000672.

    Article  PubMed  Google Scholar 

  • Hsiao CL, Lian I, Hsieh AR, Fann CS. Modeling expression quantitative trait loci in data combining ethnic populations. BMC Bioinformatics. 2010;11:111.

    Article  PubMed  Google Scholar 

  • Huang J, et al. Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression HUANG2010. Am J Psychiatry. 2010a;167(10):1254–63.

    Article  PubMed  Google Scholar 

  • Huang Y, Pastor WA, Shen Y, Tahiliani M, Liu DR, Rao A. The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLoS One. 2010b;5(1):e8888.

    Article  PubMed  Google Scholar 

  • Jin SG, Kadam S, Pfeifer GP. Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res. 2010;38(11):e125.

    Article  PubMed  Google Scholar 

  • Jin SG, Wu X, Li AX, Pfeifer GP. Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res. 2011;39(12):5015.

    Article  PubMed  CAS  Google Scholar 

  • Johnson JM, et al. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science. 2003;302(5653):2141–4.

    Article  PubMed  CAS  Google Scholar 

  • Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118–27.

    Article  PubMed  Google Scholar 

  • Johnson MB, et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron. 2009;62(4):494–509.

    Article  PubMed  CAS  Google Scholar 

  • Jones PA. The DNA methylation paradox. Trends Genet. 1999;15(1):34–7.

    Article  PubMed  CAS  Google Scholar 

  • Kang HM, Ye C, Eskin E. Accurate discovery of expression quantitative trait loci under confounding from spurious and genuine regulatory hotspots. Genetics. 2008;180(4):1909–25.

    Article  PubMed  CAS  Google Scholar 

  • Kang HJ, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011;478(7370):483–9.

    Article  PubMed  CAS  Google Scholar 

  • Kathiresan S, et al. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med Genet. 2007;8 Suppl 1:S17.

    Article  PubMed  Google Scholar 

  • Klein RJ, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385–9.

    Article  PubMed  CAS  Google Scholar 

  • Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324(5929):929–30.

    Article  PubMed  CAS  Google Scholar 

  • Kuhlmann M, et al. Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi. Nucleic Acids Res. 2005;33(19):6405–17.

    Article  PubMed  CAS  Google Scholar 

  • Kwan T, et al. Heritability of alternative splicing in the human genome. Genome Res. 2007;17(8):1210–18.

    Article  PubMed  CAS  Google Scholar 

  • Leek JT, Storey JD. Capturing heterogeneity in gene expression studies by surrogate variable analysis. PLoS Genet. 2007;3(9):1724–35.

    Article  PubMed  CAS  Google Scholar 

  • Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature. 1993;366(6453):362–5.

    Article  PubMed  CAS  Google Scholar 

  • Listgarten J, Kadie C, Schadt EE, Heckerman D. Correction for hidden confounders in the genetic analysis of gene expression. Proc Natl Acad Sci U S A. 2010;107(38):16465–70.

    Article  PubMed  CAS  Google Scholar 

  • Liu C. Brain expression quantitative trait locus mapping informs genetic studies of psychiatric diseases LIU2011. Neurosci Bull. 2011;27(2):123–33.

    Article  PubMed  Google Scholar 

  • Liu C, Cheng L, Badner JA, Zhang D, Craig DW, Redman M, Gershon ES. Whole-genome association mapping of gene expression in the human prefrontal cortex. Mol Psychiatry. 2010;15(8):779–84.

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, et al. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder LIU2011. Mol Psychiatry. 2011;16(1):2–4.

    Article  PubMed  CAS  Google Scholar 

  • Lorincz MC, Schubeler D, Hutchinson SR, Dickerson DR, Groudine M. DNA methylation density influences the stability of an epigenetic imprint and Dnmt3a/b-independent de novo methylation. Mol Cell Biol. 2002;22(21):7572–80.

    Article  PubMed  CAS  Google Scholar 

  • Majewski J, Pastinen T. The study of eQTL variations by RNA-seq: from SNPs to phenotypes. Trends Genet. 2011;27(2):72–9.

    Article  PubMed  CAS  Google Scholar 

  • Manolio TA, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–53.

    Article  PubMed  CAS  Google Scholar 

  • Marioni JC, Mason CE, Mane SM, Stephens M, Gilad Y. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 2008;18(9):1509–17.

    Article  PubMed  CAS  Google Scholar 

  • McMahon FJ, et al. Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1. Nat Genet. 2010;42(2):128–31.

    Article  PubMed  CAS  Google Scholar 

  • Melzer D, et al. A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet. 2008;4(5):e1000072.

    Article  PubMed  Google Scholar 

  • Min JL, et al. The use of genome-wide eQTL associations in lymphoblastoid cell lines to identify novel genetic pathways involved in complex traits. PLoS One. 2011;6(7):e22070.

    Article  PubMed  CAS  Google Scholar 

  • Modrek B, Resch A, Grasso C, Lee C. Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res. 2001;29(13):2850–9.

    Article  PubMed  CAS  Google Scholar 

  • Moffatt MF, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448(7152):470–3.

    Article  PubMed  CAS  Google Scholar 

  • Monks SA, Leonardson A, Zhu H, Cundiff P, Pietrusiak P, Edwards S, Phillips JW, Sachs A, Schadt EE. Genetic inheritance of gene expression in human cell lines. Am J Hum Genet. 2004;75(6):1094–105.

    Article  PubMed  CAS  Google Scholar 

  • Montgomery SB, Sammeth M, Gutierrez-Arcelus M, Lach RP, Ingle C, Nisbett J, Guigo R, Dermitzakis ET. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature. 2010;464(7289):773–7.

    Article  PubMed  CAS  Google Scholar 

  • Morley M, Molony CM, Weber TM, Devlin JL, Ewens KG, Spielman RS, Cheung VG. Genetic analysis of genome-wide variation in human gene expression. Nature. 2004;430(7001):743–7.

    Article  PubMed  CAS  Google Scholar 

  • Myers AJ, et al. A survey of genetic human cortical gene expression. Nat Genet. 2007;39(12):1494–9.

    Article  PubMed  CAS  Google Scholar 

  • Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science. 2008;320(5881):1344–9.

    Article  PubMed  CAS  Google Scholar 

  • Nembaware V, Lupindo B, Schouest K, Spillane C, Scheffler K, Seoighe C. Genome-wide survey of allele-specific splicing in humans. BMC Genomics. 2008;9:265.

    Article  PubMed  Google Scholar 

  • Nica AC, et al. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet. 2011;7(2):e1002003.

    Article  PubMed  CAS  Google Scholar 

  • Nicholson G, et al. A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection. PLoS Genet. 2011;7(9):e1002270.

    Article  PubMed  CAS  Google Scholar 

  • Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME, Cox NJ. Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet. 2010;6(4):e1000888.

    Article  PubMed  Google Scholar 

  • Pickrell JK, et al. Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature. 2010;464(7289):768–72.

    Article  PubMed  CAS  Google Scholar 

  • Powell JE, Henders AK, McRae AF, Wright MJ, Martin NG, Dermitzakis ET, Montgomery GW, Visscher PM. Genetic control of gene expression in whole blood and lymphoblastoid cell lines is largely independent. Genome Res. 2011;22(3):456–66.

    Article  PubMed  Google Scholar 

  • Purcell S, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75.

    Article  PubMed  CAS  Google Scholar 

  • Rauch TA, Wu X, Zhong X, Riggs AD, Pfeifer GP. A human B cell methylome at 100-base pair resolution. Proc Natl Acad Sci U S A. 2009;106(3):671–8.

    Article  PubMed  CAS  Google Scholar 

  • Richards AL, et al. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain. Mol Psychiatry. 2012;17(2):193–201.

    Article  PubMed  CAS  Google Scholar 

  • Schadt EE, et al. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008;6(5):e107.

    Article  PubMed  Google Scholar 

  • Schroeder A, et al. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006;7:3.

    Article  PubMed  Google Scholar 

  • Schwartz D. Genetic studies on mutant enzymes in maize. III. Control of gene action in the synthesis of Ph 7.5 esterase. Genetics. 1962;47(11):1609–15.

    PubMed  CAS  Google Scholar 

  • Sklar P, et al. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet. 2011;43(10):977–83.

    Article  CAS  Google Scholar 

  • Stegle O, Parts L, Durbin R, Winn J. A Bayesian framework to account for complex non-genetic factors in gene expression levels greatly increases power in eQTL studies. PLoS Comput Biol. 2010;6(5):e1000770.

    Article  PubMed  Google Scholar 

  • Storey JD, Madeoy J, Strout JL, Wurfel M, Ronald J, Akey JM. Gene-expression variation within and among human populations. Am J Hum Genet. 2007;80(3):502–9.

    Article  PubMed  CAS  Google Scholar 

  • Stranger BE, et al. Genome-wide associations of gene expression variation in humans. PLoS Genet. 2005;1(6):e78.

    Article  PubMed  Google Scholar 

  • Stranger BE, et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science. 2007;315(5813):848–53.

    Article  PubMed  CAS  Google Scholar 

  • Tahiliani M, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5.

    Article  PubMed  CAS  Google Scholar 

  • Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 2004;32(14):4100–8.

    Article  PubMed  CAS  Google Scholar 

  • Veyrieras JB, Kudaravalli S, Kim SY, Dermitzakis ET, Gilad Y, Stephens M, Pritchard JK. High-resolution mapping of expression-QTLs yields insight into human gene regulation. PLoS Genet. 2008;4(10):e1000214.

    Article  PubMed  Google Scholar 

  • Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57–63.

    Article  PubMed  CAS  Google Scholar 

  • Wang KS, Liu XF, Aragam N. A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophr Res. 2010;124(1–3):192–9.

    Article  PubMed  Google Scholar 

  • Webster JA, et al. Genetic control of human brain transcript expression in Alzheimer disease. Am J Hum Genet. 2009;84(4):445–58.

    Article  PubMed  CAS  Google Scholar 

  • Wheeler HE, et al. Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging. PLoS Genet. 2009;5(10):e1000685.

    Article  PubMed  Google Scholar 

  • Xu Q, Modrek B, Lee C. Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. Nucleic Acids Res. 2002;30(17):3754–66.

    Article  PubMed  CAS  Google Scholar 

  • Yuan X, et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet. 2008;83(4):520–8.

    Article  PubMed  CAS  Google Scholar 

  • Zeller T, et al. Genetics and beyond – the transcriptome of human monocytes and disease susceptibility. PLoS One. 2010;5(5):e10693.

    Article  PubMed  Google Scholar 

  • Zhang W, et al. Evaluation of genetic variation contributing to differences in gene expression between populations. Am J Hum Genet. 2008;82(3):631–40.

    Article  PubMed  CAS  Google Scholar 

  • Zhang D, et al. Genetic control of individual differences in gene-specific methylation in human brain. Am J Hum Genet. 2010;86(3):411–19.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

I would like to thank Drs. Judith Badner, Yin Yao Shugart, and Chao Chen for critical readings and comments.

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Illinois at Chicago, 900 Ashland Ave. Room 1006, Chicago, IL, 60607, USA

    Chunyu Liu

Authors
  1. Chunyu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chunyu Liu .

Editor information

Editors and Affiliations

  1. 35 Convent Drive, Bethesda, 20892, USA

    Yin Yao Shugart

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Liu, C. (2012). QTL Mapping of Molecular Traits for Studies of Human Complex Diseases. In: Shugart, Y. (eds) Applied Computational Genomics. Translational Bioinformatics, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5558-1_5

Download citation

Publish with us

Policies and ethics

Search

Navigation