PATH2220 Study Guide - Final Guide: Cardiomyopathy, Bone Marrow, Buccal Swab
Genetics and Disease
Introduction to Genetic Pathology:
• Genetic pathology → study of disease caused by variation in genetic
information
• Molecular genetics → studies genetic variation at molecular level
• DNA sequence variation
o Substitution
o Deletion
o Insertion
o Repeat → expansion/contraction
• Allelic variations
o 1 copy → hemizygous
o 2 identical copies → homozygous
o 1 reference, 1 variant copy → heterozygous
o 2 variants at differnet positions → compound heterozygous
• Chromosomes
o Genetic information at the cellular level
o Compacted DNA → 1 DNA molecule = 1 chromosomes
o DNA protein interactions → compaction, regulation of gene
expression
o Correct cellular inheritance through cellular division
o Chromosomal variation studied by cytogenetics
• Chromosomal abnormalities
o Deviations from standard pattern of 23 pairs of chromosomes with
known morphology
▪ Numeral abnormalities
▪ Structural abnormalities
o Germline mutations
▪ Pre-zygotic de novo occurrence
▪ Entire organism carries mutation
▪ Half of the gametes carry the mutation → passed to
offspring
o Somatic mutations
▪ Post-zygotic de novo occurrence
▪ Patch of affected area
▪ None of the gametes carry the mutation → cannot be
transmitted to offspring
• General inheritance patterns
o Autosomal dominant
▪ Multiple affected generations
▪ Both genders affected
▪ Male to male transition
o Autosomal recessive
▪ No transmission across generations
▪ Both genders affected
find more resources at oneclass.com
find more resources at oneclass.com
o X-linked dominant
▪ Multiple affected generations
▪ Both genders affected
▪ No male-male transmission
o X-linked recessive
▪ Only males affected
▪ Affected males linked through carrier females
▪ No male-male transmission
• Functional impact of genetic variation
o Loss of function
▪ No mRNA/protein or non-functional mRNA/protein
▪ Usually recessive
o Gain of function
▪ Extra mRNA/protein
▪ Wrong timing/location of expression
▪ New properties
▪ Usually dominant
• Factors determining genetic testing approach
o Inheritance pattern
o Disease mechanism of specific disorder
o Expected abnormality → molecular vs. cytogenetic, germline vs.
somatic
o Access to appropriate sample type
• Sample requirements
o Samples for cytogenetics → viable and dividing cells
o Samples for molecular genetics → any source of
DNA/RNA/protein
o Prenatal samples
▪ Invasive procedures (diagnostic) → chorionic villi
sampling, amniocentesis
▪ Non-invasive tests (screening) → maternal blood
o Postnatal samples
▪ Guthrie card → newborn screening
▪ Peripheral blood → common source of
cells/DNA/RNA/Proteins
▪ Buccal swab and urine → non-invasive DNA source
▪ Skin biopsy → fibroblast cell line, DNA/RNA
▪ Bone marrow → haematological disorders
▪ Pathology specimens → somatic change
• Why perform genetic tests?
o Diagnostic → patient management implications
o Presymtomatic/predictive → implement prevention or
surveillance
o Screening → large groups, early detection
o Carrier → risk to offspring
o Pharmocogenomic → drug sensitivity/resistance
o Somatic → non-heritable
find more resources at oneclass.com
find more resources at oneclass.com
