Summary
Substructured populations exhibit an overall deficiency of heterozygosity whose proportional magnitude depends on the nature of substructuring, i.e., the number of subpopulations (s), their time of divergence (t) from the ancestral population, and the rate of gene flow amongst them (m). Since apparent heterozygote deficiency could be caused by many factors other than population substructuring, one must examine the nature of substructuring that could produce the observed extent of heterozygote deficiency, in order to infer the substructuring from an observed heterozygote deficiency. Using the equivalence of proportional heterozygote deficiency and the coefficient of gene differentiation (G ST), we can generate isolines of G ST as functions of s, t (in units of 2N e generations, N e being the effective population size) and m. Analytical results suggest that large G ST values cannot be reached by substructuring alone, unless the number of subpopulations are large and they remain isolated over a long period of time. Application of the theory to population data on six variable number of tandem repeats (VNTR) loci in US Caucasians and US Blacks demonstrates that the observed heterozygote deficiencies at these loci cannot be explained by substructuring within these populations alone. This is so because such large values of G ST (3%–10%) would require an absence of gene exchange between the subpopulations and a divergence time from each other of at least 25000 years ago, neither of which is compatible with the demography and ethnohistory of US Caucasians and Blacks. In contrast, the inability to detect extreme-sized alleles and/or incomplete resolution of nearly similar-sized alleles following Southern gel electrophoresis could easily explain the observed heterozygote deficiencies. The implications of these results are discussed in the context of the forensic use of DNA-typing data, and justify the employment of population genetic principles in forensic genetics.
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References
Budowle B, Giusti AM, Waye JS, Baechtel FS, Fourney RM, Adams DE, Presley LA, Deadman HA, Monson KL (1991a) Fixed-bin analysis for statistical evaluation of continuous distributions of allelic data from VNTR loci, for use in forensic comparisons. Am J Hum Genet 48:841–855
Budowle B, Chakraborty R, Giusti AM, Eisenberg AE, Allen RC (1991b) Analysis of the VNTR locus D1S80 by the PCR followed by high-resolution PAGE. Am J Hum Genet 48:137–144
Chakraborty R, Daiger SP (1991) Polymorphisms at VNTR loci suggest homogeneity of the white population of Utah. Hum Biol 63:571–587
Chakraborty R, Danker-Hopfe H (1991) Analysis of population structure: a comparative study of different estimators of Wright's fixation indices. In: Rao CR, Chakraborty R (eds) Handbook of statistics, vol 8. Elsevier, Amsterdam, pp 203–254
Chakraborty R, Nei M (1974) Dynamics of gene differentiation between incompletely isolated populations of unequal sizes. Theor Popul Biol 5:460–469
Chakraborty R, Nei M (1978) Bottleneck effects on average heterozygosity and genetic distance with the stepwise mutation model. Evolution 31:347–356
Chakraborty R, Fornage M, Gueguen R, Boerwinkle E (1991) Population genetics of hypervariable loci: analysis of PCR based VNTR polymorphism within a population. In: Terry B, Gaudenz D, Jeffreys AJ, Wolff R (eds) DNA fingerprinting: approaches and applications. Birkhäuser, Basel, pp 127–143
Chakraborty R, Andrade M de, Daiger SP, Budowle B (1992) Apparent heterozygote deficiencies observed in DNA typing data and their implications in forensic applications. Ann Hum Genet (in press)
Clark AG (1987) Neutrality tests of highly polymorphic restriction-fragment-length polymorphisms. Am J Hum Genet 41:948–956
Cohen JE (1990) DNA fingerprinting for forensic identification: potential effects on data interpretation of subpopulation hetero-geneity and band number variability. Am J Hum Genet 46:358–368
Devlin B, Risch N, Roeger K (1990) No excess of homozygosity at loci used for DNA fingerprinting. Science 24:1416–1420
Edwards A, Hammond L, Jin L, Caskey T, Chakraborty R (1992) Population genetics of trimeric and tetrameric tandem repeats for four human ethnic groups. Genomics 12 (in press)
Flint J, Boyce AJ, Martinson JJ, Clegg JB (1989) Population bottlenecks in Polynesia revealed by minisatellites. Hum Genet 83:257–263
Gart JJ, Namm J (1984) A score test for the possible presence of recessive alleles in generalized ABO-like genetic systems. Biometrics 40:887–894
Jeffreys AJ, Royle NJ, Wilson V, Wong Z (1988) Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA. Nature 332:278–281
Jeffreys AJ, Neumann R, Wilson V (1990) Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis. Cell 60:473–485
Kennedy RJR (1944) Single or triple melting-pot? Intermarriage trends in New Haven, 1870–1940. Am J Sociol 49:331–339
Lander ES (1989) DNA fingerprinting on trial. Nature 339:501–505
Lander ES (1991) Research on DNA typing catching up with courtroom application. Am J Hum Genet 48:819–823
Li CC (1969) Population subdivision with respect to multiple alleles. Ann Hum Genet 33:23–29
Li WH (1976) Effect of migration on genetic distance. Am Nat 110:841–847
Maruyama T (1970) Effective number of alleles in a subdivided population. Theor Popul Biol 1:273–306
Milkman R, Beatty LD (1970) Large-scale electrophoretic studies of allelic variation in Mytilusedulis. Biol Bull 139:430
Neel JV (1973) “Private” genetic variants and the frequency of mutation among Sough American Indians. Proc Natl Acad Sci USA 70:3311–3315
Nei M (1965) Variation and covariation of gene frequencies in subdivided populations. Evolution 19:256–258
Nei M (1973) Analysis of gene diversity in subdivided populations. Proc Natl Acad Sci USA 70:3321–3323
Nei M (1975) Molecular population genetics and evolution. North-Holland, Amsterdam New York
Nei M (1977) F-statistics and analysis of gene diversity in sub-divided populations. Ann Hum Genet 41:225–233
Nei M (1986) Definition and estimation of fixation indices. Evolution 40:643–645
Nei M (1987) Molecular evolutionary genetics. Columbia University Press, New York
Nei M, Chesser RK (1983) Estimation of fixation indices and gene diversities. Ann Hum Genet 47:253–259
Nei M, Feldman M (1972) Identity of genes by descent within and between populations under mutation and migration pressures. Theor Popul Biol 3:460–465
Nei M, Roychoudhury AK (1982) Genetic realtionship and evolution of human races. Evol Biol 14:1–59
Nei M, Maruyama T, Chakraborty R (1975) The bottleneck effect and genetic variability in populations. Evolution 29:1–10
Ohta T (1977) Genetic variation in multigene families. Nature 267:515–517
Skibinski DOF, Beardmore JA, Cross TF (1983) Aspects of the population genetics of Mytilus (Mytilidae; Mollusca) in the ritish Isles. Biol J Linn Soc 19:137–183
Slatkin M (1985) Rare alleles as indicators of gene flow. Evolution 39:53–65
Spuhler JN, Clark PJ (1961) Migration into human breeding population of Ann Arbor, Michigan, 1900–1950. Hum Biol 33:223–231
Wolff RK, Nakamura Y, White R (1988) Molecular characterization of a spontaneously generated new allele at a VNTR locus: no exchange of flanking DNA sequences. Genomics 3:347–351
Wong Z, Wilson V, Patel I, Povey S, Jeffreys AJ (1987) Characterization of panel of highly variable minisatellites cloned from human DNA. Ann Hum Genet 51:269–288
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Chakraborty, R., Jin, L. Heterozygote deficiency, population substructure and their implications in DNA fingerprinting. Hum Genet 88, 267–272 (1992). https://doi.org/10.1007/BF00197257
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DOI: https://doi.org/10.1007/BF00197257