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DNA based genetic analysis has been an essential part in modern biomedical research. Professor Sir Alec Jeffreys first used multilocus DNA analyses to determine the relationship between individuals in an immigration case, and heralded a new field, DNA fingerprinting or DNA forensics. Nowadays, almost all DNA markers, those that reside on autosomal chromosomes, Y chromosomes and mitochondria DNA (mtDNA), have been utilized in DNA forensic investigations. The Short Tandem Repeats (STR) markers on autosomal chromosomes are the cornerstone of current DNA crime databases. Investigations are also extended to Y chromosomes and mtDNA for paternal and maternal lineage comparisons, respectively. Panels based on Single Nucleotide Polymorphisms (SNP) were also developed as an adjunct tool in forensics, especially for degraded samples. Discovery of block structure of human genome offers new avenues for future exploration. DNA forensics involves three main applications: transfer evidence evaluation (i.e., compare DNA profiles of evidence samples with those of known subjects), mixture interpretation (i.e., determine the number of contributors in mixture sample and identify the possible contributors), and kinship analysis (i.e., identify the relationships between individuals). All DNA materials (e.g. STR, SNP, Y chromosome, mtDNA etc.) could be exploited for these applications. Applications will be more complicated by incorporating both population substructure and mutation of DNA markers.This study is conducted to enhance forensic applications for complex situations with DNA analyses. First, a new algorithm for identifying missing persons based on autosomal markers (i.e., STR or SNP) was developed by incorporating both population substructure and mutation. The software was validated by the International Commission on Missing Persons. Second, I developed two maximum likelihood methods with population substructure to interpret DNA mixture evidence base on SNPs. Third, a new type of forensic marker, haplotype block, based on the block structure of the human genome was developed, which has a higher discriminating power than those of individual SNPs and is particularly useful for kinship analyses. Fourth, a Y chromosome STR database (i.e., SWGDAM Y STR database) was characterized. Basic principles for interpreting Y STR evidence profiles were suggested, and mutation patterns of Y STR were described. Finally, a new independence test was developed to evaluate the independence between autosomal chromosomes, Y chromosome and mtDNA, so when appropriate the weight of evidence for each marker group can be combined. |
