Human Genomic Variation

  • Carsten Carlberg
  • Stine Marie Ulven
  • Ferdinand Molnár


Due to partial isolation of human populations during history, their genetic variation is geographically diverted. Positive natural selection, i.e. the force that drives the increase in prevalence of advantageous traits, has played a central role in human evolution. Genetic differences between human populations are most pronounced in tissues, such as the skin, the intestinal tract or the immune system, that are directly affected by the environment. This led not only to obvious differences in skin color among the populations, but also in different resistance to diseases and diversity in dietary intake, such as the ability to digest milk sugar (lactose). The genetic basis of the variation of human populations and individuals has recently been studied and catalogued by large consortia, such as the HapMap Project and the 1000 Genomes Project. They obtained data via genome-wide genotyping and whole genome sequencing of 2504 subjects and thus allow the study and analysis of the relation of human genomic variation and disease risk.

In this chapter, we will briefly describe the genetic adaption of the anatomically modern human to new geographic and climatic environments in Asia and Europe and the challenges provided by the shift from hunters and gatherers to farmers (Chap.  4). We will discuss how complex phenotypic traits influence the risk to develop diseases, such a T2D and CVD (Chaps.  10 and  11). Each complex disease is based on dozens to hundreds of gene variants, such as single nucleotide polymorphisms (SNPs) and structural variants, such as copy number variations (CNVs). We will describe how the HapMap Project and the 1000 Genomes Project map these genetic variants in different human populations. In this context, we will discuss how whole genome sequencing can result in the identification of rare SNPs that significantly contribute to complex traits and diseases.


Human evolution Human populations Single nucleotide variants Copy number variants Haplotype blocks Next-generation sequencing HapMap Project Genome-wide association studies 1000 Genomes Project 

Additional Reading

  1. 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR (2015) A global reference for human genetic variation. Nature 526:68–74CrossRefGoogle Scholar
  2. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65CrossRefPubMedGoogle Scholar
  3. Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F et al (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467:52–58CrossRefPubMedGoogle Scholar
  4. Haraksingh RR, Snyder MP (2013) Impacts of variation in the human genome on gene regulation. J Mol Biol 425:3970–3977CrossRefPubMedGoogle Scholar
  5. Manolio TA (2010) Genomewide association studies and assessment of the risk of disease. N Engl J Med 363:166–176CrossRefPubMedGoogle Scholar
  6. Pääbo S (2014) The human condition – a molecular approach. Cell 157:216–226CrossRefPubMedGoogle Scholar
  7. Shendure J, Lieberman Aiden E (2012) The expanding scope of DNA sequencing. Nat Biotechnol 30:1084–1094CrossRefPubMedPubMedCentralGoogle Scholar
  8. Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, Zhang Y, Ye K, Jun G, Hsi-Yang Fritz M, Konkel MK, Malhotra A, Stütz AM, Shi X, Paolo Casale F, Chen J, Hormozdiari F, Dayama G, Chen K, Malig M, Chaisson MJ, Walter K, Meiers S, Kashin S, Garrison E, Auton A, Lam HY, Jasmine Mu X, Alkan C, Antaki D, Bae T, Cerveira E, Chines P, Chong Z, Clarke L, Dal E, Ding L, Emery S, Fan X, Gujral M, Kahveci F, Kidd JM, Kong Y, Lameijer EW, McCarthy S, Flicek P, Gibbs RA, Marth G, Mason CE, Menelaou A, Muzny DM, Nelson BJ, Noor A, Parrish NF, Pendleton M, Quitadamo A, Raeder B, Schadt EE, Romanovitch M, Schlattl A, Sebra R, Shabalin AA, Untergasser A, Walker JA, Wang M, Yu F, Zhang C, Zhang J, Zheng-Bradley X, Zhou W, Zichner T, Sebat J, Batzer MA, McCarroll SA, 1000 Genomes Project Consortium, Mills RE, Gerstein MB, Bashir A, Stegle O, Devine SE, Lee C, Eichler EE, Korbel JO (2015) An integrated map of structural variation in 2,504 human genomes. Nature 526:75–81CrossRefPubMedPubMedCentralGoogle Scholar
  9. Veeramah KR, Hammer MF (2014) The impact of whole-genome sequencing on the reconstruction of human population history. Nat Rev Genet 15:149–162CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Carsten Carlberg
    • 1
  • Stine Marie Ulven
    • 2
  • Ferdinand Molnár
    • 3
  1. 1.Institute of BiomedicineUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of NutritionUniversity of OsloOsloNorway
  3. 3.School of PharmacyUniversity of Easterm FinlandKuopioFinland

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