Unit 7 - Mitochondrial Genetics and Forensic DNA Analysis

Question 1

where are mitochondrial diseases most serious?

Answer 1

in CNS and muscle

• usually related to tissues where there’s a high degree of oxidative phosphorylation activity
• commonly neuropathies, encephalopathies, and myopathies

Question 2

are mitochondria self sufficient?

Answer 2

no, their full function is linked to nuclear genes

• some processes are governed by mitochondrial genes, others by nuclear genes
• thus, defects in mitochondrial function could be autosomal or X-linked mutations of nuclear genome, or mutations of mitochondrial DNA itself

Question 3

matrilineal inheritance

Answer 3

mitochondria transmitted in egg cytoplasm

-few, if any mitochondria present in pronucleus of sperm

Question 4

homoplasmy

Answer 4

homozygosity for one or more cytoplasmic genes

-usually refers to population of mitochondria that all have same genetic composition

Question 5

heteroplasmy

Answer 5

heterozygosity for one or more cytoplasmic genes

• two or more different populations of mitochondria are present in a cell
• heteroplasmy in cytoplasm is analogous heterozygosity in nucleus

Question 6

how can a mother be heteroplasmic?

Answer 6

mother may be unaffected, but have affected children, or vice versa

• mother must have low frequency of mutated cells, but passes higher frequencies to children who express disease, or vise versa
• require 85% mutant mitochondria in cell for disease to manifest

Question 7

why are mitochondrial disorders often progressive with late onset? how is this explained?

Answer 7

due to increase, over time, in numbers of mutations per cell and numbers of mutant cells
-replicative segregation in oogenesis (relative proportions of mutant mitochondria can increase or decrease) or acquired mutations (that undergo replicative segregation, but not transmitted to progeny)

Question 8

what is MERRF?

Answer 8

myoclonic epilepsy with ragged red fiber disease

-mitochondrial disorder that shows bnormally staining mitochondria

Question 9

what is forensic DNA analysis?

Answer 9

both nuclear and mitochondrial DNA used

• sequence variability with high degree of polymorphism
• nuclear DNA is more robust, for hypervariable minisatellite regions and DNA fingerprinting

Question 10

what are sources of error for DNA analysis?

Answer 10

quality of specimen

• poor sample collection/preparation
• mislabeling/handling error
• degradation or contamination

Question 11

statistical analysis and interpretation

Answer 11

• analyze sufficient number of polymorphisms with high degree of variability
• consider allele frequencies vary between populations
• consider differences in allele frequencies in different racial and ethnic groups

Question 12

what can mitochondrial DNA analysis be used for?

Answer 12

• maternal inheritance
• siblings carry same mDNA
• link individuals by comparing maternal mitochondrial lineages
• family identity (NOT individual identity)

Question 13

paternity and medicine

Answer 13

include or exclude putative father based on biological evidence

• minimum of 2 probes
• frequency of alleles in families differ from population frequencies

Question 14

what is CODIS?

Answer 14

combined DNA information system

• all 50 states, US army, FBI, US Navy, Department of Justice –> all state, local, and federal law enforcement agencies
• enables all crime labs to exchange and compare DNA profiles electronically, to link crimes to each other and to convicted offenders

Question 15

what can be different between identical twins?

Answer 15

• fingerprints
• blood
• hair
• footprints

can have environmental variation