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
Disorders that involved __ __ typically have an autosomal recessive mode of inheritance
defective enzymes
What are examples of autosomal recessive disorders?
Albanism
Cystic Fibrosis
Tay-Sachs Disease
What is the most common lethal genetic disease among caucasians?
Cystic fibrosis (CF)
Describe cystic fibrosis
gene encodes CFTR which regulates ion transport across the cell membrane
Mutant allele creates an altered CFTR protein leading to ion imbalance
