Chapter 5- Complicating Inheritance Flashcards
Factors influencing inheritance
Multiple Alleles
Codominance
Incomplete dominance
Penetrance
Heterogeneity
Mitochondial genes
Linkage
Multiple Alleles
More than two forms of allele in population
Individual expresses at most two
Examples- ABO blood types and HLA Genes
Codominance
Heterozygotes express both alleles
Example- ABO blood types
Epistasis
Multiple gene interactions on phenotype
Labrador Coat Phenotypes
Gene B controls melanin density
Dominant- black coat, recessive- brown
Gene E controls deposition
Dominant- Normal, recessive- None, yellow
Gene D controls melanin production
Dominant- Full, normal; recessive- dilute, silver
Penetrance
Chance that an individual with a particular allele with display the phenotype
Reduced penetrance- Some individuals will no show symptoms
Autosomal dominant heritability
Variable Expression
Expression of different degrees of the phenotype, varying severity
Will always show some symptoms
Causes- Environment, modifier genes, Allelic heterogeneity
Allelic Heterogeneity
Many different mutations on same gene cause similar diseases
Locus Heterogeneity
Mutations on different genes can cause similar diseases
Example- Polycystic kidney disease can result from mutations on chromosome 16 or 4
Pleiotropy
Single genotype causes many phenotypic expressions
Impacts many bodily systems
Phenocopy
Environmental influences cause traits that appear to be inherited
Huntington’s Disease
Autosomal dominant progressive brain disorder
Mutation of Huntingtin (HTT) gene
Expansion of glutamine triplets cause misfolding and protein aggregation
Impair basal ganglia function
Defects in motor, cognitive, and psychiatric domains
Mitochondrial Genome
Independent, unique
37 genes- 13 ETC, 2 rRNA, 22 tRNA
Many copies
Maternal inheritance
High mutation rate
Heteroplasmy
Heteroplasmy
Copies of mitochondrial DNA are not identical
Segregation during cell division is random and unorganized
Phenotype is dependent on if mutant DNA is above threshold
Mitochondrial Disease Pedigree
All children regardless of sex inherit DNA
Only develop symptoms if above threshold
Maternal transmission only
Leber’s Hereditary Optic Neuropathy (LHON)
Sudden bilateral blindness ~27 years old
Reduced penetrance
Defects in NADH dehydrogenase
Linked Genes
Close together loci that do not segregate independently
Inherited together as haplotype
Recombination rate less than 50%
Genetic Mapping
1% recombination = 1 map unit
1 map unit = 1 centimorgan (cM)
Recombination frequency= recombinant progeny over total progeny
Human Gene Mapping
Collect pedigrees of families with disease of interest
Analyze genetic markers throughout genome
Perform statistical analysis
Compared linked genes with pedigree data
Analyze linked gene functions for mechanism
Genetic Statistical Analysis
LOD Scores
Odds genes are linked on the same chromosome
LOD score over 3 is significant
Amyotrophic Lateral Sclerosis (ALS)
Lou Gehrig’s Disease
Progressive lethal motor neuron disease
Kills motor neurons in brain and spinal cord
Death by muscle atrophy and diaphragm paralysis
Familial mutations in SOD1 gene encoding CuZn superoxide dismutase
Abberant chemistry or protein aggregation causes cell death
