Apparent heterozygote deficiencies observed in DNA typing data and their implications in forensic applications

R. Chakraborty, Mariza De Andrade, S. P. Daiger, B. Budowle

Research output: Contribution to journalArticle

236 Citations (Scopus)

Abstract

Restriction fragment length polymorphisms (RFLP) analysis using the Southern blot technique can be used to recognize copy number variation of variable number of tandem repeats (VNTR) of conserved core sequences at several regions of the human genome. This new class of polymorphisms reveals a high degree of genetic variation, useful for individual identification purposes. Criticisms against forensic applications of such DNA typing data include the limitation of employing Hardy-Weinberg expectation of genotype frequencies, since several surveys indicate apparent deficiency of heterozygosity (or excess homozygosity) in comparison with Hardy-Weinberg expectations. This research postulates an alternative explanation of deficiency of apparent heterozygosity which is caused by the inability to detect extremely small-sized alleles (called 'non-detectable' alleles) due to the sensitivity of Southern gel electrophoresis. We show that the presence of 'non-detectable' alleles can produce pseudo-homozygosity and their frequencies can be predicted from the observed proportional heterozygote deficiency. Furthermore, in the covert presence of such 'non-detectable' alleles, we show that the gene-count method provides over-estimates of allele frequencies in the sample population, and hence the Hardy-Weinberg predictions of genotype frequencies avoid wrongful bias against suspects in forensic applications of DNA typing data. Applications of this theory to population data on six VNTR loci in US Caucasians and US Blacks suggest that the presence of 'non-detectable' alleles could be the major cause of apparent heterozygote deficiency, and the current approaches of predicting the population frequency of specific DNA phenotypes are practically free of the possible wrongful bias in courtroom applications of DNA typing data.

Original languageEnglish (US)
Pages (from-to)45-57
Number of pages13
JournalAnnals of Human Genetics
Volume56
Issue number1
StatePublished - 1992
Externally publishedYes

Fingerprint

DNA Fingerprinting
Heterozygote
Alleles
Minisatellite Repeats
Genotype
Conserved Sequence
Population Dynamics
Human Genome
Southern Blotting
Gene Frequency
Restriction Fragment Length Polymorphisms
Population
Electrophoresis
Gels
Phenotype
DNA
Research
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Apparent heterozygote deficiencies observed in DNA typing data and their implications in forensic applications. / Chakraborty, R.; De Andrade, Mariza; Daiger, S. P.; Budowle, B.

In: Annals of Human Genetics, Vol. 56, No. 1, 1992, p. 45-57.

Research output: Contribution to journalArticle

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