Anthro Notes Sept. 20/12
- The field of genetics has a long history and key developments are the understanding of genetic
transmission in families and populations, and the understanding of the molecular structure of genetic
transmission. This together with advances in technology, particularly extracting DNA from tissue
using PCR and sequencing the results, is the foundation of modern forensic genetic analysis. In the
last two decades, the field of forensic science has changed dramatically due to genetic science and the
admissibility of science in the courts. It is important to have a historical perspective to illustrate the
long but disjointed development of the field and to emphasize the pace of change due to the
exponential growth of molecular genetics.
- History: 1865 Mendels Laws (discovered in 1900). 1908 Hardy-Weinberg Theorem. 1953
Watson-Crick. 1977 Sequencing (Sanger method). 1981 Human mitochondrial genome
completely sequenced. 1985 PCR invented. 1987 First forensic case using RFLP. 1991 First
paper on STRs. DNA Identification Act and TWGDAM. 1995-1999 First DNA STR databases in UK,
US, and Canada. 2002 SNP technology. 2003 Human genome project completed.
- Cytogenetics: Cytogenetics is the study of genetic mechanisms that operate within the context of a
cell. In the human cell there are 23 pairs of chromosomes (46 total) in the nucleus, and in the
cytoplasm another hereditary structure exists called the mitochondrion. Both chromosomes and
mitochondria are made of DNA. DNA is present in the nucleus (nuclear DNA) and in the
mitochondrion (mtDNA). In each cell there are hundreds of mitochondria. Because all the mtDNA is
the same, the mitochondria is often called the 47 chromosome. mtDNA only comes from the mother.
- In the human nuclear karyotype, DNA is located on long linear structures called chromosomes. When
a new individual is formed by an egg being fertilized by a sperm, the new individual (zygote) receives
23 chromosomes from each parent. Females have two X chromosomes (receive X from each parent)
and males have an X and a Y (Y comes from father). Since the new individual has 46 chromosomes
and eventually has to transmit his or her DNA to the next generation, the 46 is reduced to 23 by a cell
division process called meiosis. The Y chromosome is smaller and has fewer genes (exons). In
forensics, junk DNA (introns) is studied, not the exons. The Y chromosome has many polymorphisms
that are forensically valuable, especially in sexual assault cases.
- Mendels Laws: In 1865, Mendel published two key laws of genetics. Law 1 Segregation: States that
a simple genetic trait is determined by a pair of separate factors (now called alleles), one inherited
from each parent intact (discrete) from generation to generation (do not blend). Law 2
Independent Assortment: Deals with the inheritance of two or more traits and states that each pair of
alleles behaves independently of other pairs. Thus it is possible to predict the statistical probabilities
of matings. This law provides basis for the product rule of probability. The laws are fundamental to
forensic DNA analysis and form the basis for determining random match probabilities. The term gene
is used to indicate any heritable unit and allele is used to represent variable forms (number of
repeats in nuclear DNA testing) of the gene. Genes that code for proteins are called exons.
- If there is mating between two homozygotes (BB and bb), the offspring will all be phenotypically B,
but genotypically Bb. The recessive allele does not show in the heterozygote state. This is called a null
allele. There are no null alleles in DNA analysis, but if a sample is highly degraded sometimes the
DNA of one of the alleles is destroyed, resulting in an erroneous interpretation. The loss of an allele is
called allelic dropout.- Hardy-Weinberg genetics: In 1908, Hardy and Weinberg detailed the laws of heredity at the
population level which is a fundamental model for population genetics. The basic formula for a
diallelc (two allele) system is: a + b = 1. The mating expansion of this is , where
is the relative frequency of the aa genotype (homozygous STRs), is the relative frequency of the bb
genotype (homozygous STRs), and 2ab is the relative frequency of the heterozygote. The HW
equilibrium model assumes that populations are ideal (stable) and the statistical expansion is used to
determine if subsets of forensic DNA data are suitable for making judgements about alleles sampled
in forensic cases. Until DNA profiles are regarded as being sufficiently distinctive to establish
individuality, forensic arguments are going to assign probabilities on the basis of proportions of
marker types (STRs) in populations (blacks, whites, etc) that are stored in databanks and databases.
- The allele pool: The collective genotype of the population is known as the allele pool. Even though
allele frequencies remain constant, the genotypic relative frequencies differ through time.
- Watson and Crick discovered the structure and function of DNA. In 1953, they published a paper in
Nature titled Molecular Structure of Nucleic Acids: a structure for deoxyribonucleic acid. This article
formed the basis for understanding heredity at the molecular level, including how proteins are made
via a pathway between DNA, mRNA and transfer RNA. At one time it was thought that most of the
DNA was used to code for proteins (protein synthesis), but we now know that less than 5% of our
genome is made up of structural (exons) genes. Most of it is made up of non-coding repeated
segments that are now used in forensic DNA analysis. Watson and Crick postulated that the base
pairings they found (A-T and C-G) would have important implications. Today the base pair rule forms
the basis of all our sequencing technology.
- DNA structure and reactivity: The tightly wound helix protects the bases which are connected by a