Principles of Human Genetics and Mendelian Inheritance

  • Dominique P. GermainEmail author
  • Iulia E. Jurca-Simina


Every species has a particular series of inherited characteristics (traits), which determines a developmental plan and distinguishes one species from another. Differences between individuals of the same species (variations) are the result of genetic, epigenetic, and/or environmental factors. As the molecular support of heredity of any living organism, genes are transmitted from parents to offspring during the process of reproduction. A gene is the basic physical and functional unit of heredity. The concept of gene was recently redefined as a locatable region of genomic sequence, corresponding to a unit of inheritance, associated with regulatory regions, transcribed regions, and/or other functional sequence regions.


  1. 1.
    Griffiths AJF, Pearson H. Genetics: what is a gene? Nature. 2006;441:398–401.CrossRefGoogle Scholar
  2. 2.
    Watson JD, Crick FHC. Molecular structure of nucleic acids: a structure for desoxyribose nucleic acid. Nature. 1953;171:737–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Collins FS, Morgan M, Patrinos A. The human genome project: lessons from large scale biology. Science. 2003;300:286–90.CrossRefPubMedGoogle Scholar
  4. 4.
    Ecker JR, Bickmore WA, Barroso I, Pritchard JK, Gilad Y, Segal E. Genomics: ENCODE explained. Nature. 2012;489:52–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Kim MS, Pinto SM, Getnet D, Nirujogi RS, Manda SS, Chaerkady R, et al. A draft map of the human proteome. Nature. 2014;509:575–81.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Doudna JA, Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346:1258096.CrossRefPubMedGoogle Scholar
  7. 7.
    Griffiths AJF, et al. An introduction to genetic analysis. 10th ed. New York: W H Freeman & Company; 2012.Google Scholar
  8. 8.
    Brown TA. Genomes. 2nd ed. Oxford: Wiley-Liss; 2002.Google Scholar
  9. 9.
    Germain DP. Gaucher’s disease: a paradigm for interventional genetics. Clin Genet. 2004;65:77–86.CrossRefPubMedGoogle Scholar
  10. 10.
    Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, et al. Treatment of Fabry’s disease with the pharmacologic chaperone Migalastat. N Engl J Med. 2016;375:545–55.CrossRefPubMedGoogle Scholar
  11. 11.
    Popp MW-L, Maquat LE. Organizing principles of mammalian nonsense-mediated mRNA decay. Annu Rev Genet. 2013;47:139–65.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Turnpenny PD, Ellard S. Emery’s elements of medical genetics. 14th ed. Philadelphia: Elsevier; 2012.Google Scholar
  13. 13.
    Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, et al. Aberrant 50 splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Nucleic Acids Res. 2007;35:4250–63.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Mendel JG. Versuche über Pflanzenhybriden Verhandlungen des naturforschenden Vereines in Brünn. Abhandlungen: Bd. IV für das Jahr; 1865. p. 3–47.Google Scholar
  16. 16.
    Bodmer WF, Cavalli-Sforza LL. Genetics, Evolution, and Man. W. H. Freeman and Company; 1976.Google Scholar
  17. 17.
    Hartl DL, Jones EW. Genetics—principles and analysis. 4th ed. Sudbury: Jones and Bartlett Publishers; 1998.Google Scholar
  18. 18.
    Roach ES. Sickle cell trait: innocent until proven guilty. Arch Neurol. 2005;62:1781–2.CrossRefPubMedGoogle Scholar
  19. 19.
    Nussbaum RL, McInnes RR, Willard HF. Thompson & Thompson genetics in medicine. 8th ed. Philadelphia: Elsevier; 2015.Google Scholar
  20. 20.
    Veltman JA, Brunner HG. De novo mutations in human genetic disease. Nat Rev Genet. 2012;13:565–75.CrossRefPubMedGoogle Scholar
  21. 21.
    Acuna-Hidalgo R, Bo T, Kwint MP, van de Vorst M, Pinelli M, Veltman JA, Hoischen A, Vissers LE, Gilissen C. Post-zygotic point mutations are an under-recognized source of de novo genomic variation. Am J Hum Genet. 2015;97:67–74.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Goldstein JL, Brown MS. History of discovery: the LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Germain DP. Ehlers-Danlos syndrome type IV. Orphanet J Rare Dis. 2007;2:32.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Bittles AH. Consanguinity and its relevance to clinical genetics. Clin Genet. 2001;60:89–98.CrossRefPubMedGoogle Scholar
  25. 25.
    Bittles AH, Black ML. Consanguinity, human evolution, and complex diseases. Proc Natl Acad Sci. 2010;107:1779–86.CrossRefPubMedGoogle Scholar
  26. 26.
    Hamamy H, Antonarakis SE, Cavalli-Sforza LL, Temtamy S, Romeo G, Kate LP, et al. Consanguineous marriages, pearls and perils: Geneva International Consanguinity Workshop report. Genet Med. 2011;13:841–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Zlotogora J, Bach G, Munnich A. Molecular basis of Mendelian disorders among Jews. Mol Genet Metab. 2000;69:169–80.CrossRefPubMedGoogle Scholar
  28. 28.
    Zeevi DA, Altarescu G, Weinberg-Shukron A, Zahdeh F, Dinur T, Chicco G, et al. Proof-of-principle rapid noninvasive prenatal diagnosis of autosomal recessive founder mutations. J Clin Invest. 2015;125:3757–65.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Sidransky E. Gaucher Disease: insights from a rare Mendelian disorder. Discov Med. 2012;14:273–81.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Diaz GA, Gelb BD, Risch N, Nygaard TG, Frisch A, Cohen IJ, et al. Gaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutations. Am J Hum Genet. 2000;66:1821–32.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kishnani PS, Corzo D, Nicolino M, et al. Recombinant human acid [altha]-glucosidase: major clinical benefits in infantile onset Pompe disease. Neurology. 2007;68(2):99–109.CrossRefPubMedGoogle Scholar
  32. 32.
    Kroos M, Hoogeveen-Westerveld M, Michelakakis H, Pomponio R, van der Ploeg A, Halley D, et al. Update of the Pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants. Hum Mutat. 2012;33:1161–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Dobyns WB, Filauro A, Tomson BN, Chan AS, Ho AW, Ting NT, et al. Inheritance of most X-linked traits is not dominant or recessive, just X-linked. Am J Med Genet. 2004;129:136–43.CrossRefGoogle Scholar
  34. 34.
    Harper PS. Practical genetic counselling. 7th ed. London: CRC Press; 2010.Google Scholar
  35. 35.
    Lyon MF. Gene action in the X-chromosome of the mouse (mus musculus L.). Nature. 1961;190:372–3.CrossRefPubMedGoogle Scholar
  36. 36.
    Minks J, Robinson WP, Brown CJ. A skewed view of X chromosome inactivation. J Clin Invest. 2008;118:20–3.CrossRefPubMedGoogle Scholar
  37. 37.
    Amos-Landgraf JM, Cottle A, Plenge RM, Friez M, Schwartz CE, Longshore J, et al. X chromosome-inactivation patterns of 1,005 phenotypically unaffected females. Am J Hum Genet. 2006;79:493–9.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Echevarria L, Benistan K, Toussaint A, Dubourg O, Hagège AA, Eladari D, et al. X-chromosome inactivation in female patients with Fabry disease. Clin Genet. 2016;89:44–54.CrossRefGoogle Scholar
  39. 39.
    Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434:400–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Dominique P. Germain
    • 1
    Email author
  • Iulia E. Jurca-Simina
    • 1
    • 2
  1. 1.Division of Medical GeneticsUniversity of VersaillesMontignyFrance
  2. 2.Center of Genomic MedicineVictor Babes University of Medicine and PharmacyTimisoaraRomania

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