Mitochondrial and Forensic Genetics

Question 1

mitochondrial diseases

Answer 1

• mutations of ox/phos
• most serious in CNS and muscle
• neuropathies, encephalopathies, myopathies
• tissues with high use of ox/phos

Question 2

mitochondria

Answer 2

• full function linked to nuclear genes
• defects of mitochondrial function may show autosomal or X linked pattern
• not self sufficient

Question 3

matrilineal inheritance

Answer 3

• mitochondria transmitted in egg cytoplasm
• few if any present in pro-nucleus of sperm
• mitochondria passed through from mom only

Question 4

homoplasmy

Answer 4

• homozygosity for one or more cytoplasmic genes
• usually refers to a population of mitochondria that all have the same genetic composition
• children of affected mother will most likely be affected
• no children of affected males with be affected
• if its a nuclear gene, inheritance pattern will be the same

Question 5

heteroplasmy

Answer 5

• heterozygosity for one or more cytoplasmic genes
• rules of inheritance change
• mother may be unaffected and have affected children
• mother has low frequency of mutated cells and passes on higher freq to kids- express
• or pass low freq (even if she is affected)- won’t express disease
• -if 85% of the cell or greater is made of mutant mito, the cell will have dysfunction
• for disease to be expressed, need large number of dysfunctional cells

Question 6

replicative segregation

Answer 6

• mito disorders are usually progressive with late onset
• due to increase in numbers or mutations per cell and number of mutant cells
• as cells divide, relative proportions of mutant mito may change over time
• can increase or decrease
• can also acquire new mutation due to mito high mutation rate- wouldn’t be transmitted since formed in somatic cells

Question 7

case study

Answer 7

• learning delay, muscle jerks, seizures
• increase in seizures, loss of muscle tone, vision and hearing problems
• initial pedigree and myoclonic epilepsy with ragged red fiber disease
• needed to rule out new mutation-but found heteroplasmy and maternal transmission of a mutation
• mom also had symptoms, uncle, grandmother, could all be attributed to something else. older sister had mild hearing loss and one seizure at 10
• found A to G mutation in maternal side- varies in expression due to heteroplasmy

Question 8

conclusions about mito

Answer 8

• complex group of diseases
• diagnosis complicated by heteroplasmy and variable expression
• maternal inheritance
• progressive nature of disease
• include possibility of mitochondrial disorder in ddx or a patient with unexplained neuro defects

Question 9

forensic DNA analysis

Answer 9

• popularized by TV
• originally brought the attention of public with trial of OJ simpson
• currently accepted in many disciplines
• use of DNA technologies to obtain information on the genetic identity of an individual and how that relates to a criminal, medical, or scientific investigation

Question 10

DNA analysis

Answer 10

• sequence variability with a high degree of polymorphism
• nuclear DNA has hypervariable minisatellite regions that are used in DNA fingerprinting
• want to examine regions with highest degree of polymorphism

Question 11

sources of error

Answer 11

quality of specimen:
-poor sample collection
-mislabeling or handling error
-poor sample prep
-degradation
-contamination
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

Question 12

guidelines

Answer 12

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

Question 13

applications

Answer 13

• identification
• criminal justice
• medicine
• scientific studies-research, historical info

Question 14

mito DNA analysis

Answer 14

• human id
• maternal inheritance
• siblings carry the same mito DNA
• link individuals by comparing maternal mito lineages
• family id, not individual
• more hardy DNA

Question 15

Tomb of the Unknown Soldier

Answer 15

• one of 3 individuals
• used mito DNA to link family and found out who it was
• must be maternally related

Question 16

identification

Answer 16

• forensic testing of nuclear DNA will allow unique identification of individuals
• military-requires service personnel to be DNA fingerprinted for later id
• mass disaster
• criminal cases
• medical cases

Question 17

twin studies

Answer 17

• DNA can tell difference between identical and fraternal twins
• identical should share alleles and fraternal are like normal siblings

Question 18

paternity and medicine

Answer 18

• include or exclude a putative father based on biological evidence
• min of 2 probes
• freq of alleles in families differs from population freq
• can find out which DNA came from dad first by screening against mom and then test various fathers
• need unique and specific data

Question 19

criminal justice

Answer 19

• exclusions
• inclusions
• link multiple events
• post conviction relief
• CODIS

Question 20

CODIS

Answer 20

-combined DNA Information System
-all 50 states, US army, FBI, navy, DOJ, all state, local, and federal law enforcement agencies
-enables crime labs to exchange and compare DNA profiles electronically, thereby linking crimes to each other and to convicted offenders
-

Question 21

quiz

Answer 21

• crime scene with fingerprints, blood, hair, footprints
• identical twins confess-both have motive and opportunity
• can exclude based on fingerprints
• one persons blood might have different pathogens

Question 22

Romanovs

Answer 22

• last royal family of Russia
• arrested, house arrest, executed
• found bodies, evidence of violent deaths, tsar, tsarina, 3 kids, 3 servants, doctor
• used X and Y probes, repeat seq to establish nuclear family
• follow with mito studies
• family group and 4 others
• tsarina and 3 daughters connected by mito via maternal living relative
• nicholas more difficult-two maternally related, not 100% match
• then exhumed brother and found that the two of them were heteroplasmic and living relatives were homoplasmic
• anastasia?- anna anderson manahan did not match, she was actually polish, not her, used colon- didn’t match parents or prince phillip, matched a maucher instead

Question 23

anastasia and alexi?

Answer 23

• cremated
• then found in 2007
• male 12-15, female 15-19
• alexi was 14, anastasia was 17
• used mito DNA again
• complete concurrence
• STR analysis had consistent markers for a nuclear family
• final link- blood from nicholas’s shirt matched skull and alexi and living paternal relative, matched 100% at 17 markers

Question 24

romanov conclusions

Answer 24

• combined approach of classical forensics with DNA forensics
• correct age of remains, sexes, ages of skeletons
• STR data confirmed the romanov family, physician, 3 servants
• mito DNA confirmed romanov family
• Y-STR confirmed that final male skeleton is paternally related to nicholas
• DNA estimates 1.3 x10^8 more likely to be romanovs than another random group of individuals

Question 25

king tut

Answer 25

• microsatellite data revealed family relationships and connected king tut to the previously unidentified mummy of his father
• contributions from great grandfather, great grandmother on grandmothers side, and grandfather are indicated
• tut’s mom and dad were siblings
• cause of tut’s death- damage consistent with chariot accident, but also has plasmodium- malaria?
• two fetal mummies directly related to tut
• tut’s wife also thought to be one of his sisters

Question 26

thomas jefferson

Answer 26

• father sally hemings children?
• DNA studies were performed on living male descendents of Jefferson and hemings songs
• Jefferson Y DNA revealed rare haplotype
• the same haplotype was detected in descendants of easton hemings- sally’s last son
• could have been any male in Jefferson’s family, but DNA does connect two families through Sally

Question 27

general conclusions

Answer 27

• many different applications for DNA analysis
• genomic DNA-specific ID
• mito DNA- family, evolution
• mito and forensic DNA analysis can be applied to a very diverse set of questions that go beyond medicine, but with an underlying theme of genetics
• forensic DNA studies are successful because they utilize biological principles