Chapter 24: Medical Genetics Flashcards
Many genetic diseases exhibit __ __, which means that they may be caused by mutations in more than one gene
locus heterogeneity
What are autosomal recessive diseases usually caused by?
loss-of-function mutations
What are three explanations for autosomal dominant diseases?
haploinsufficiency
gain-of-function mutations
dominant-negative mutations
Be familiar with the seven observations that determine a disease is genetic
- An individual who exhibits the disease is more likely to have genetic relatives with the disorder than of someone in the general population
- Identical twins share the disease more than nonidentical twins
- The disease does not spread to individuals sharing a similar environment
- Different populations tend to have different frequencies of the disease
- The disease tends to develop at a characteristic age (age of onset)
- The human disorder may resemble a disorder that is already known to have a genetic basis in animals
- A correlation is observed between a distance and a mutant human gene or a chromosomal alteration
Define autosomal in terms of disease
gene associated with disease is on an autosome, not a sex chromosome
What are the four characteristics of an autosomal recessive inheritance?
- Frequently, an affected offspring has two unaffected parents
- When two unaffected heterozygotes have children, the percentage of an affected child on average is 25%
- Two affected individuals have 100% affected children
- The trait occurs within the same frequency in both sexes
What are the five common characteristics of an autosomal dominant inheritance?
- An affected offspring usually has one or two affected parents
- An affected individual with only one affected parent is expected to produce 50% on average affected off spring
- Two affected, heterozygous individual have on average, 25% unaffected off spring
- The trait occurs with the same frequency in both sexes
- For most dominant, disease-causing alleles, the homozygous is more severely affected with the disorder, in some cases dominance may be lethal
What is haploinsufficency?
a copy does not produce a normal phenotype (50% of functional protein is not enough to produce a normal phenotype)
Define gain-of-function mutations
changes a gene product so that it gains a new/ abnormal function
Define dominant-negative mutation
alters the gene product in a way that acts antagonistically to the normal gene
Why are males more affected when it comes to x-linked diseases?
Because they are hemizygous (only have a single copy)
What are the three characteristics of an x-linked recessive inheritance?
- Males are much more likely to exhibit the trait
- Mothers of affected males often have brothers/fathers who are also affected
- Daughters of affected males, on average, produce 50% affected sons
What are two characteristics of an x-linked dominant inheritance?
- Only females exhibit the trait when it is lethal to males
- Affected mothers have a 50% chance of passing the trait to their daughters
Define a prion
disease-causing agent composed entirely of protein
Why can a prion cause disease?
Prion protein in the abnormal conformation (PrP^Sc) can convert a protein in the normal form (PrP^C) to the abnormal conformation
What is the difference between monozygotic (MZ) twins and dizygotic (DZ) twins?
monozygotic- formed from the same sperm and egg
Dizygotic - formed from separate pairs of sperm and egg
Define concordance
degree to which a trait is inherited, refers to the percentage of twin pairs in which both twins exhibit the disorder or trait
Define age of onset
characteristic age a disease develops
What is an example of an autosomal dominant disorder?
Huntington’s disease
mutation in gene that encodes a protein termed huntingtin - adds polyglutamine tract to protein - causes an aggregation of proteins in neurons
What are four autosomal dominant disorders?
Huntington’s
Achondroplasia
Polydactyly
Brachydactyly
Syndactyly
