Mitochondrial and Forensic Genetics Flashcards
1
Q
mitochondrial diseases
A
- mutations of ox/phos
- most serious in CNS and muscle
- neuropathies, encephalopathies, myopathies
- tissues with high use of ox/phos
2
Q
mitochondria
A
- full function linked to nuclear genes
- defects of mitochondrial function may show autosomal or X linked pattern
- not self sufficient
3
Q
matrilineal inheritance
A
- mitochondria transmitted in egg cytoplasm
- few if any present in pro-nucleus of sperm
- mitochondria passed through from mom only
4
Q
homoplasmy
A
- 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
5
Q
heteroplasmy
A
- 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
6
Q
replicative segregation
A
- 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
7
Q
case study
A
- 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
8
Q
conclusions about mito
A
- 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
9
Q
forensic DNA analysis
A
- 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
10
Q
DNA analysis
A
- 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
11
Q
sources of error
A
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
12
Q
guidelines
A
- 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
13
Q
applications
A
- identification
- criminal justice
- medicine
- scientific studies-research, historical info
14
Q
mito DNA analysis
A
- human id
- maternal inheritance
- siblings carry the same mito DNA
- link individuals by comparing maternal mito lineages
- family id, not individual
- more hardy DNA
15
Q
Tomb of the Unknown Soldier
A
- one of 3 individuals
- used mito DNA to link family and found out who it was
- must be maternally related
16
Q
identification
A
- 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
17
Q
twin studies
A
- DNA can tell difference between identical and fraternal twins
- identical should share alleles and fraternal are like normal siblings
18
Q
paternity and medicine
A
- 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
19
Q
criminal justice
A
- exclusions
- inclusions
- link multiple events
- post conviction relief
- CODIS
20
Q
CODIS
A
-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
-
21
Q
quiz
A
- 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
22
Q
Romanovs
A
- 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
23
Q
anastasia and alexi?
A
- 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
24
Q
romanov conclusions
A
- 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
25
Q
king tut
A
- 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
26
Q
thomas jefferson
A
- 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
27
Q
general conclusions
A
- 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
