Mitochondrial Genetics and Forensic DNA Analysis Flashcards Preview

MS 1 Unit 7 MCP > Mitochondrial Genetics and Forensic DNA Analysis > Flashcards

Flashcards in Mitochondrial Genetics and Forensic DNA Analysis Deck (21):

Mitochondrial DNA: The Forgotten Genomes

-since the nuclear chromosomal DNA is so prominent these days, it is often easy to forget there is a second set of genetic information located in cells
-Mitochondria are organelles located in the cytoplasm of the cell and contain their own DNA and are thus another source of DNA


Mitochondrial Diseases

-mutations of ox/phosp
-most serious in CNS and muscle
-commonly include: neuropathies, encephalopathies, myopathies
-the effects of mitochondrial mutations can occur in a broad range of tissues and organs, but they usually are related to tissues in which there is a high degree of ox/pho activity.



-full function linked to nuclear genes
-defects of mitochondrial function may show autosomal or X-linked pattern of inheritance
-mitochondrial function is dependent on nuclear genes
-some processes are governed by mitochondrial genes and others by nuclear genes
-therefore defects in mitochondrial function could be due to autosomal or X-linked mutations of the nuclear genome, or mutations in the mitochondrial DNA itself


Matrilineal Inheritance

-mitochondria transmitted in egg cytoplasm
-few if any mitochondria present in the pronucleus of the sperm



-homozygosity for one or more cytoplasmic gene
-usually refers to a population of mitochondrial that all have the same genetic composition



-when there are two or more different populations of mitochondria are present in a cell.
-heteroplasmy in the cytoplasm in analogous heterozygosity in the nucleus
-if the mother is heteroplasmic, the rules of inheritance change slightly
-the mother may be unaffected and yet have affected children. This can occur if the mother has a low frequency of mutant cells but passes higher frequencies on to her children who then express the disease
-if the mother is heteroplasmic and affected, she may pass a low frequency of mutant mitochondria to her children who would be unaffected
-thus, within families, there may be a difference in the expression of the same disease
-in general, the more mutant mitochondria, the more severe the disease
-in order for any given cell to express dysfunction, there must be a high proportion of mutant mitochondria present in that cell (85%)
-for the disease to be manifested in an individual, there must be a large number of such dysfunctional mitochondria throughout the body or within a target organ or tissue


Mitochondria disorders progressive

-mitochondrial disorders often are progressive with late onset
-this is due to an increase, over time, in the numbers of mutations per cell and the numbers of mutant cells
-one mechanism that explains this is replicative segregation. As cells divide, the relative proportions of mutant mitochondria may change over time
-the frequency of mutation within a clone can increase or decrease. If an individual had a low, non-pathogenic frequency initially, it is possible that as he/she gets older, the disease may manifest due to the growing population of defective mitochondria that did not previously exist
-because there is high mutation rate in mitochondrial DNA, it is possible for a mutation to occur as a new event (acquired mutation) and then proliferate in the population, again generating an subpopulation of mutant mitochondria. This type of mutation is analogous to acquired nuclear mutations associated with cancer. Because these mutations occur in the somatic cells, they would not be transmitted to progeny
-these mechanisms also predict that under certain conditions, mutations may be lost from the cell population


Conclusion of Mitochondrial Stuff

-complex group of diseases
-diagnosis complicated by: heteroplasmy and variable expression, maternal inheritance, progressive nature of disease
-include possibility of mitochondrial disorder in the differential diagnosis of a patient with unexplained neurological defects


Forensic DNA Analysis

-Use of DNA technologies (PCR, RFLP, sequencing) to obtain information on the genetic identity of an individual and how that relates to a criminal, medical, or scientific investigation
-popularized by TV
-originally brought to the attention of the public with the OJ Simpson trial- 1995
-currently accepted in many disciplines


DNA Analysis

-sequence variability with a high degree of polymorphism
-nuclear DNA: hypervariable minisatellite regions, DNA fingerprinting
-both nuclear and mitochondrial DNA are used in forensics
-key features include the ability to uniquely identify the DNA
-to do this, you want to examine regions of the DNA that have the highest degree of polymorphism
-in the nuclear DNA, it has been shown that the hypervariable ministatellite regions have the most variability and these are the regions that have been utilized in DNA fingerprinting


Sources of Error

-quality of specimen
-poor sample collection
-mislabeling or handling error
-poor sample preparation
-statistical analysis and interpretation
-analyze a sufficient number of polymorphisms with a high degree of variability
-consider that allele frequencies vary between populations
-consider differences in allele frequencies in different racial and ethnic groups



-standards for collecting and preserving specimens- limit possible contamination
-chain of custody for specimens
-standardization of techniques for handling and processing samples
-accreditation of laboratories
-relevance of technology must be established


Mitochondrial DNA Analysis

-human identity:
-maternal inheritance
-siblings carry the same mitochondrial DNA
-link individuals by comparing maternal mitochondrial lineages
-family identity- not individual identity


Tomb of Unknown Soldier

-bones placed in Tomb of Unknown Soldier were known to be from one of 3 different individuals
-testing of mitochondrial DNA from the bones and maternally related individuals from all 3 families provided a positive match to one family. The bones were removed and buried by the family because now the identity was known
-these types of tests are excellent at matching family members but are not specific enough to identify of a particular individual. Any testing that is done must be confirmed using at least 2 different known individuals from the family- all maternally related



-forensic testing of nuclear DNA will allow unique identification of individuals
-mass disaster
-criminal cases
-medical cases


Twin studies

-can tell the difference between identical and fraternal twins
-fraternal twins will be no more similar than other siblings in the family (central pair), whereas identical twins (outer pairs) should share all of their alleles


Paternity and Medicine

-include or exclude a putative father based on biological evidence
-minimum of 2 probes
-frequency of alleles in families differs from population frequency
-some paternity tests are uninformative- that is it provides no information that can chose between suspects
-what you want is for the study to be informative with the data being unique and specific



database that allows many agencies to share their information
-this provides information across the country rather than restricting it to one city or state
-searches can be done that may identify a criminal who has committed crimes in multiple locations



-traditional forensics- evidence of violent death
-DNA analysis- X and Y probes, repeat sequence to establish nuclear family, follow with mitochondrial studies to confirm identify
-nuclear DNA
-Mitochondrial DNA- direct connection between one older female and the 3 younger daughters
-it was slightly unclear because Nicholas was heteroplasmic
-Anna Anderson Manahan aka Anastasia
-Anastasia and Alexia were cremated- bones found and could be confirmed
-mitochondrial DNA confirmed
-STR analysis supportered
-blood stain on Nicholas' shirt in the Hermitage Museum final link and living relatie of the Romanov family (paternal descent)
-Y-STR Analysis Nicholas and living relative of Romanov family


King Tut

-microsatellite analysis revealed family relationships and connected King Tut to the previosuly unidentified mummy of his father
-cause of death chariot accident
-DNA specific for Plasmodium falciparum (malaria)
-offspring who died in utero
-Tut's wife unknown but one of sisters


Thomas Jefferson

-did he father children by his slave, Sally Hemings?
-DNA studies were performed on living male descendents of Jefferson and Hemings' sons
-Jefferson: Y DNA analysis revealed a very rare haplotype
-the same haplotype was detected in descendents of Easton Hemings- Sally's last son
-DNA from:
-5 male descendants of Jefferson's paternal uncle
-6 male descendents of Sally Hemings' son Woodson and Eston Hemings
-3 male descendents of John Carr- grandfather of Jefferson's daughters son
-Jefferson Y DNA has a unique haplotype
-Woodson and Carr descendents have significantly different than the Jefferson DNA
-Eston Y DNA matches the Jefferson Y DNA
-it could have been any male in Jefferson's family