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The costs of human inbreeding and their implications for variations at the DNA level

Abstract

An analysis of the world literature on the children of first cousin marriages reveals that the depression of survival in offspring followed from birth (including late miscarriages; at about six months gestation or later) to a median age of 10 years is constant (4.4% ± 4.6) across a wide range of values for population prereproductive mortality. There is thus no evidence for the action of conditional lethals. On the basis of these data, it is calculated that the average human is heterozygous for only 1.4 lethal equivalents capable of acting over this portion of the life cycle. The implications of these results are discussed in the context of genetic counseling, and the biomedical significance of variation in DNA.

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References

  1. Basu, S.K. Effects of consanguinity among Muslim groups of India. Medical Genetics in India, vol 2 (ed. Verfna, I.C.) 173–187 (Auroma, Pondfcherry, 1978).

    Google Scholar 

  2. Rao, P.S.S. & Inbaraj, S.G. Inbreeding effects on human reproduction in Tamil Nadu of South India. Ann. hum. Genet. 41, 87–98 (1977).

    Article  CAS  PubMed  Google Scholar 

  3. Rao, P.S.S. & Inbaraj, S.G. Trends in human reproductive wastage in relation to long-term practice of inbreeding. Ann. hum. Genet. 42, 401–413 (1979).

    Article  CAS  PubMed  Google Scholar 

  4. Bittles, A.H., Shami, S.A. & Appaji Rao, N. Consanguineous marriage in Southern Asia: Incidence, causes and effects Minority Populations: Genetics, Demography and Health (etis Bittles, A.H. & Roberts, D.F.) 102–118 (MacMillan, London, 1992).

    Chapter  Google Scholar 

  5. Shami, S.A. & Study of consanguineous marriages in the population of Lahore (Punjab), Pakistan. Biologia 28, 1–15 (1982).

    Google Scholar 

  6. Shami, S.A. & Iqbal, I. Consanguineous marriages in the population of Sheikhupura (Punjab), Pakistan. Biologia 29, 231–244 (1983).

    CAS  PubMed  Google Scholar 

  7. Shami, S.A. & Hussain, S.B. Consanguinity in the population of Gujrat (Punjab), Pakistan. Biologia 30, 93–109 (1984).

    Google Scholar 

  8. Shami, S.A. & Minnas, I.B. Effects of consanguineous marriages on offspring mortality in the City of Jhelum (Punjab), Pakistan. Biologia 30, 153–165 (1984).

    Google Scholar 

  9. Shami, S.A. & Siddiqui, H. The effects of parental consanguinity in Rawalpindi City (Punjab), Pakistan. Biologia. 30, 189–200 (1984).

    Google Scholar 

  10. Bittles, A.H., Grant, J.C. & Shami, S.A. An evaluation of consanguinity as a determinant of reproductive behaviour and mortality in Pakistan. Int. J. Epidemiol. 22, 463–467 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Schull, W.J. Empirical risks in consanguineous marriages: Sex ratio, malformation, and viability. Am. J. hum. Genet. 10, 294–343 (1958).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Neel, J.V. & Schull, W.J. The effect of inbreeding on mortality and morbidity in two Japanese cities. Proc. natn. Acad. Sci. U.S.A. 48, 573–582 (1962).

    Article  CAS  Google Scholar 

  13. Yamaguchi, M., Yanase, T., Nagano, H.N. Effects of inbreeding on mortality in Fukuoka population. Am. J. hum. Genet. 22, 145–159 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Schull, W.J., Nagano, H., Yamamoto, M. & Komatsu, I. The effects of parental consanguinity and inbreeding in Hirado, Japan I. Stillbirths and prereproductive mortality. Am. J. hum. Genet. 22, 239–262 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Komai, T. & Tanaka, K. Genetic studies on inbreeding in some Japanese populations. II. The study of school children in Shizuoka: History, frequencies of consanguineous marriages and their subtypes, and comparibility in socioeconomic status among consanguinity classes. Jpn. J. hum. Genet. 17, 114–148 (1972).

    CAS  Google Scholar 

  16. Tanaka, K. Genetic studies on inbreeding in some Japanese populations. XI. Effects of inbreeding on mortality in Shizuoka. Jpn. J. hum. Genet. 17, 319–331 (1973).

    CAS  Google Scholar 

  17. AI-Awadi, S.A., Naguib, K.K., Moussa, M.A., Farag, T.I., Teebi, A.S. & El-Khalifa, M.Y. The effect of consanguineous marriages on reproductive wastage. Clin. Genet. 29, 384–388 (1986).

    Article  Google Scholar 

  18. Scott-Emuakpor, A.B. The mutation load in an African population. I. An analysis of consanguineous marriages in Nigeria. Am. J. hum. Genet. 26, 674–687 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Salzano, P.M., Margallo, F.A., Freire-Maia,N. & Krieger, H. Genetic load in Brazilian Indians. Acts Genet. Statist. Med. 12, 212–218 (1962).

    CAS  Google Scholar 

  20. Freire-Maia, N., Freire-Maia, A. & Quelce-Salgado, A. The load of lethal mutations in White and Negro populations. I. First survey. Acta Genet Statist. Med. 13, 185–198 (1963).

    CAS  PubMed  Google Scholar 

  21. Freire-Maia, N. The load of lethal mutations in White and Negro populations. II. Second survey. Acta Genet. Statist. Med. 13, 199–225 (1963).

    CAS  PubMed  Google Scholar 

  22. Freire-Maia, N., Chautard-Freire-Maia, E.A., Barbosa, C.A.A. & Krieger, H. Inbreeding studies in Brasilian schoolchildren. II. Inbreeding effect on infant mortality. Am. J. med. Genet. 16, 331–355 (1983).

    Article  Google Scholar 

  23. Sutter, J. & Tabah, L. Structure de la mortalité dans les families consanguines. Population 8, 511–526 (1953).

    Article  Google Scholar 

  24. Bittles, A.H., Mason, W.M., Greene, J. & Rao, N.A. Reproductive behavior and health in consanguineous marriages. Science 252, 789–794 (1991).

    Article  CAS  PubMed  Google Scholar 

  25. Schull, W.J. & Neel, J.V. The effects of inbreeding on Japanese children (Harper and Row, New York, 1965).

    Google Scholar 

  26. Spielman, R.S., Neel, J.V. & Li, F.H.F. Inbreeding estimation from population data: Models, procedures, and implications. Genetics 85, 335–371 (1977).

    Google Scholar 

  27. Stern, C., Carson, G., Kinst, M., Novitski, E. & Uphoff, D. The viability of heterozygotes for lethals. Genetics 37, 413–449 (1952).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Hiraizumi, Y. & Crow, J.F. Heterozygous effects on viability, fertility, rate of development and longevity of Drosophila chromosomes that are lethal when homozygous. Genetics 45, 1071–1083 (1960).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Mukai, T., Chigusa, S.I., Mettler, L.E. & Crow, J.F. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics 72, 335–355 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Grahn, D., Leslie, W.P., Verkey, F.A. & Lea, R.A. Determination of the radiation-induced rate for sex-linked lethals and detrimentals in the mouse. Mut Res. 15, 331–347 (1972).

    Article  CAS  Google Scholar 

  31. Fields, C., Adams, M.D., White, O. & Vente, J.C. How many genes in the human genome? Nature Genet. 7, 345–346 (1994).

    Article  CAS  PubMed  Google Scholar 

  32. Jeffreys, A.J. DNA sequence variants in the Gγ, Aγ, δ, and β-globin genes of man. Cell 18, 1–10 (1979).

    Article  CAS  PubMed  Google Scholar 

  33. Ewens, W.J., Spielman, R.S. & Harris, H. Estimation of genetic variation at the DNA level from restriction endonuclease data. Proc. natn. Acad. Sci. U.S.A. 78, 3748–3750 (1981).

    Article  CAS  Google Scholar 

  34. Karth, J.H. & Cavalli-Sforza, L.L. Notes on individual sequence variation in humans: Immunoglobulin kappa light chain. Am. J. hum. Genet. 54, 1037–1041 (1994).

    Google Scholar 

  35. Li, W.-H. & Sadler, L.A. Low nucleotide diversity in man. Genetics 129, 513–523 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Fullerton, S.M., Harding, R.M., Boyce, A.J. & Clegg, J.B. Molecular and population genetic analysis of allelic sequence diversity at the human β-globin locus. Proc. natn. Acad. Sci. U.S.A. 91, 1805–1809 (1994).

    Article  CAS  Google Scholar 

  37. Hofker, M.H., Wapenaar, M.C., Goor, N., Bakker, E., van Ommen, G.J.B. & Pearson, P.L. Isolation of probes detecting RFLPs from X-chromosome specific libraries: Potential use for diagnosis of Duchenne muscular dystrophy. Hum. Genet. 70, 148–156 (1985).

    Article  CAS  PubMed  Google Scholar 

  38. Satoh, C., Takahashi, N., Asakawa, J., Hiyama, K. & Kodaira, M. Variations among the Japanese of the factor IX gene (F9) detected by PCR-denaturing gradient gel electrophoresis. Am. J. hum. Genet. 52, 167–175 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Cooper, D.N., Smith, B.A., Cooke, H.J., Nieman, S. & Schmidtke, J. An estimate of unique DNA sequence heterozygosity in the human genome. Hum. Genet. 69, 201–205 (1984).

    Article  Google Scholar 

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Bittles, A., Neel, J. The costs of human inbreeding and their implications for variations at the DNA level. Nat Genet 8, 117–121 (1994). https://doi.org/10.1038/ng1094-117

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