Human Genetic Disease Flashcards
Congenital
Disorder present at birth
Single gene disorders can be…
Autosomal dominant
Autosomal recessive
X-linked dominant
Mono genic defect
Single-gene disorder
Types of aetiological disorders
Single gene/monogenic
Mitochondrial
Chromosomal imbalance
Or multifactorial (includes enviro)
Examples of single gene disorders
Cystic fibrosis
phenylketonuria
Autosomal dominant disorders can be…
Gain of function or loss is function
Examples of autosomal dominant disorders
Huntington’s
Familial breast cancer (BRCA1)
_____ are more likely to suffer from x linked disorders
Males
Anticipation
When a disorder gets worse with each generation
Females may show c-linked diseases less severely due to
X-chromosome inactivation
Examples of x-linked diseases
Fragile x syndrome
Duchenne muscular dystrophy
Complexity in single gene disorders
Generic heterogeneity:
Same phenotype, different genetic loci
Penetrance: when a phenotype is not expressed regardless of presence of allele
Expressivity: degree of expression
Mosaicisism: when not all cells are genetically identical
Phenology: when an environmental factor can lead to the same phenotype as a genetic disorder
Genomic imprinting: when expressivity depends on which parent the disease allele was inherited from
Multifactorial vs complex diseases
Multifactorial = affected by enviro
Complex = affected by multiple genes
Types of chromosomal mutations
Non-disjunction
Translocation (balances or unbalanced)
Functions encoded in mitochondrial DNA
13 Respiratory chain subunits
tRNA for each amino acid
12S and 16S rRNA for mitochondrial ribosomes
Mitochondrial disorders could be due to mutations in___
Mitochondrial or nuclear DNA
homoplasmic vs heteroplasmic
Homoplasmic: all the mitochondria in the cell have the same DNA
Population bottleneck of heteroplamia
Due to the small number of mitochondria passed from mother to oogonia
Return to homoplamic after a few generation be
Genetic disorders that may have been selected for
Cystic fibrosis - have fewer attachment points for cholera therefore immunity
Sickle cell anaemia: helps prevent malaria
Both are advantageous when heterozygous but deadly when homozygous
Molecular basis of recessive vs dominant traits
Recessive: takes two non-functioning gene copies to be below threshold
*haplosufficient
Dominant: only takes one non functioning gene to be below threshold
*haploinsufficient
Allelic vs non-allelic genetic heterogeneity
Allelic: mutations in same gene but different phenotypes (ie. dif alleles = dif phenotype)
Non-allelic: mutations in different genes but similar phenotypes
Methods for observing genetic basis of a trait/disorder
Compare incidence in a family compared to general population
Compare monozygotic twins
Ploidy of mitochondrial genome
2-10
Mitochondrial genome transplant
In vitro fertilization > removal of pronuclei > pronuclei added to cell with healthy mitochondria
Or
Spindle chromosomes are removed from unfertilized egg > added to egg with good mitochondria and no genome > in vitro fertilization