Genetics Review Flashcards
Codominance
Both alleles contribute to phenotype. Example is blood groups or A1AT deficiency
Variable Expressivity
Where a phenotype varies in individuals with an given genotype. Example, NF1 (different disease severity with same mutation in ch 18
Incomplete Penetrance
Where not everybody with a given mutation shows the phenotype. BRCA1 gene mutations don’t always cause cancer.
Pleiotropy
One gene mutation can have many effects. PKU can have light skin, intellectual disability and musty body odor.
Anticipation
Where a genetic disease passed down increases in severity or presents earlier. Trinucleotide repeats.
Loss of heterozygosity
Essentially the two hit hypothesis. Loss of Rb doesn’t cause cancer, but loss of 2 does. This is shown with tumor suppressors, not oncogenes.
Dominant Negative mutation
This is where a mutated allele asserts dominant effects over another normal allele. The mutation of a transcription factor in its allosteric site. Nonfunctioning mutants can still bind DNA preventing wild-type tfs from binding.
Linkage Disequilibrium
In a population, the expected percentage of a phenotype due to independent assortment is altered because of two genes proximity on the chromosome. Genes can be inherited together. Can vary in different populations
Mosaicism
Where errors in mitosis after fertilization cause multiple genotypes in different cells. This is different than lyonization because these cells have the same genotype. Somatic mosaicism is where the mutation propagates through multiple tissues or organs. Gonadal mosaicism is where a mutation is only in eggs or sperm cells to affect offspring.
McCune Albright Syndrome
An example of mosaicism: a mutation in Gs-alpha subunit is survivable if mosaic, but not if somatic. Causes cafe-au-lait spots that do not cross the midline. Fibrous bones at the base of skull and in the femur.
Locus heterogeneity
Mutations at different loci can cause similar phenotypes. Like albanism or mutations that cause marfanoid phenotypes.
Allelic heterogeneity
Different mutations in the same locus produce the same phenotype. Like beta-thalassemia.
Allelic heterogeneity
Different mutations in the same locus produce the same phenotype. Like beta-thalassemia.
Heteroplasmy
The presence of both normal and mutated mitochondrial DNA allowing for different severities of a mitochondrial disease.
Heteroplasmy
The presence of both normal and mutated mitochondrial DNA allowing for different severities of a mitochondrial disease.
Uniparental Disomy
Where an offspring receives two copies of a chromosome from one parent and none from the other. Heterodisomy indicates a meiosis 1 error. Isodisomy is a meiosis 2 error. This is a euploid state and becomes important if a child is showing a recessive disease that only one parent is a carrier for.
Hardy-Weinberg population genetics
A technique to analyze the frequency of a gene or genotype in a population assuming that mating is random, national selection isn’t occurring, no migration, and no mutation is occurring. P+Q=1 and P2+2PQ+Q2=1
P indicates the frequency of a particular allele.
P2 indicates the frequency of a particular genotype.
However, this all changes if the disease is X linked because it will be P for males and P2 for women.
Imprinting
At some loci only one allele is active, the other is inactivated by methylation in a process called imprinting.
Imprinting
At some loci only one allele is active, the other is inactivated by methylation in a process called imprinting. With one allele imprinted, the deletion of the active allele leads to disease.
Angelman syndrome or prader willi syndrome are examples. This can also occur as a result of uniparental disomy.
Prader-Willi syndrome
Marental allele is imprinted, deletion of the Paternal allele on chromosome 15 leads to hyperphagia, intellectual disability, hypogonadism, and hypotonia. 25% of cases are due to maternal uniparental disomy where two maternally imprinted genes are received.
Angelman Syndrome
Paternal gene is imprinted and maternal gene is deleted on chromosome 15. This results in the happy puppet phenomenon. Inappropriate laughter, seizures, ataxia, severe disability.
How to tell if autosomal dominant?
All generations affected.
How to tell if autosomal recessive?
Usually only one generation affected. Increased risk in inbreeding.
How to tell if X-linked recessive?
Affected mother will pass mutation to all sons. Carrier mom will pass mutation to 50% of sons.
How to tell if X-linked dominant
Father will pass mutation to all daughters but no sons. Mother will pass to 50% of sons.
Hypophosphatemic Rickets
Example of an x-linked dominant disease. Inherited disorder that causes phosphate wasting at proximal tubule causing a rickets-like presentation.
How to tell if mitochondrial inheritance?
Transmitted only through the mother, all offspring of affected female will have disease. Variable expression in a population or even a family due to heteroplasmy.
