Forensic Genetics Overview

DNA Polymorphisms and Human Identification

• DNA polymorphisms are variations in DNA sequences shared by a percentage of a population.
• They range from a single base pair to thousands of base pairs.
• Polymorphisms are frequent in some regions of the genome, like the HLA locus, important for immune self-identity.

Types of Polymorphisms

• RFLP Typing (Restriction Fragment Length Polymorphism):
  • Identifies differences in DNA fragment sizes after restriction enzyme digestion.
  • Used for genetic mapping, parentage testing, and human identification.
  • Requires specific restriction enzymes, DNA size analysis (Southern blot).
• VNTR Typing (Variable Number Tandem Repeats):
  • Based on repeated sequences.
  • Detected using Southern blot.
• STR Typing (Short Tandem Repeats/Microsatellites):
  • Short repeated sequences of 1-10 base pairs.
  • Amplified by PCR.
  • Used for human identification, parentage testing.
  • Advantages: efficient amplification, minimal DNA needed.
• SNP Typing (Single Nucleotide Polymorphism):
  • Single nucleotide differences.
  • Detected by sequencing.
  • Used for genetic mapping of disease genes, population studies.
• Mitochondrial DNA Typing:
  • Used for human identification, especially in cases where nuclear DNA is degraded.
  • Inheritance is maternal.
• Protein-based Identification:
  • Protein polymorphisms, amino acid sequence variations.
  • Can be used as an alternative or supplementary forensic method.

Objectives

• Compare and contrast different types of polymorphisms.
• Define RFLP and its use in genetic mapping, parentage testing, and human identification.
• Describe STR structure and nomenclature.
• Relate STR use in parentage testing and gender identification (amelogenin locus).
• Explain matching probabilities and allele frequencies in matching.
• Describe Y-STR use in forensic and lineage studies.

Linkage Analysis

• Family Histories: Analyzing multiple generations of affected individuals for shared STR alleles.
• Population Studies: Identifying STR alleles common in certain populations or ethnic groups.
• Sibling Analyses: Determining the likelihood of relatedness between individuals by analyzing shared alleles.
• Mapping Genes: Using STRs as markers to pinpoint the location of genes involved in diseases.

Bone Marrow Engraftment Testing

• Alleles: The unique genetic characteristics (alleles) of DNA in recipient and donor.
• Quality Assurance: Ensures the integrity and accurate identification of tissue in surgical specimens.

Single Nucleotide Polymorphisms

• Definition: Variations in the nucleotide sequence affecting a single base.
• Importance: Used in genetic and disease mapping and for forensic studies.
• Frequency: Relatively common, with one SNP observed every 300 nucleotides in the human genome.
• Identification: Detected by direct sequencing, using next-generation methods.

HapMap Project

• Objective: Mapping haplotypes— sequences of SNPs commonly inherited together.
• Methodology: Sequencing DNA to detect common SNPs, then identifying haplotype blocks.
• Significance: Used to identify disease-related genes, for improving understanding of human ancestry.

Mitochondrial DNA Polymorphisms

• Circular genome, 16,569 base pairs.
• Maternal inheritance.
• Variations in the hypervariable regions (HV1 and HV2) offer high resolution in identification.
• Used in forensic comparisons, ancestry studies, and disease research.

Advanced Concepts

• Matching Profiles: Using the frequency of alleles in the population to evaluate matching odds.
• Linkage Analysis: Establishing a connection between an STR marker and a trait or disease.
• Chimerism: Presence of two or more distinct genetic populations in one individual (e.g. after a stem-cell transplant).
• Paternity and Sibship Testing: Determining the likelihood of a stated relationship using allele frequencies and shared alleles or the absence thereof.
• STR nomenclature: System by which STR loci are named.
• Quantitative Methods in Engraftment Testing: Measuring the proportion of donor/recipient peak heights to identify engraftment.
• Epigenetic Analysis: Examining DNA methylation changes to detect differences in individuals or groups.