Lecture 30 and 31 Flashcards
Dominant trait
effects of a variant allele are observed in the presence of a normal allele (heterozygous)
Recessive trait
effects of a variant allele are observed only in the absence of a normal allele (homozygous)
Autosomal
chromosomes 1-22
Sex-linked
X and Y chromosomes
Inheritance of autosomal dominant trait
results in a 50% chance of passing trait to each child
only one parent has mutated gene
Unaffected siblings do not transmit the disorder
Age of onset is delayed for some autosomal dominant diseases don’t see the full effect until later in life
Huntington disease
Inheritance of autosomal recessive trait
only sees the trait if both parents have the mutant gene
25% chance of having an affected child
50 % chance carrier child
25% chance non carrier
All child of affected parents are carriers
Age onset is early in life for many conditions because the gene can be passed on through carriers
Symptoms tend to be more uniform
Penetrance
some show mutated genes and others do not
Any trait associated with the variant
Complete= 100%
Incomplete= < 100%
Expressivity
how a gene expresses itself in an individual person
Number, identity, extent of severity
Ranges from complete to minimal
Affected by other genes, exposure to harmful conditions, environment, age
Genetic variant
permanent change in the sequence of the gene
Pathogenic variant
change in the sequence of gene responsible for causing the disease
well supported by scientific research
often referred to as mutations
Silent mutations
do not have any impact on protein function of the gene
Missense mutations
change identity of a single nucleotide, can have more impact on protein function.
Does not have any impact on the nucleotide that is encoded
malfunctioning protein
Nonsense mutations
single nucleotide change and changes to a stop codon
causes a shortened or nonfunctional protein to be expressed
Likely pathogenic
probably responsible for causing disease
not enough scientific research
Uncertain significance
not conformed to cause disease
not enough scientific research
Likely benign
probably responsible for causing disease
not enough research to be sure
Benign
not responsible for causing disease
strong scientific research to rule out link to disease
Insertions
change the number of nucleotides present in the gene
encounter a stop codon
insert 1 or 2 nucleotides can cause a frameshift
Deletions
delete a single nucleotide
results in a malfunctioning protein
What are the three types of mutations that cause autosomal dominant disorders?
- Loss of function
- Gain of function (PCSK9)
- Dominant negatives: inhibits activity of unmuted copy
Which types of mutation cause recessive disorders
Caused by loss of function
- Cystic fibrosis caused by loss-of-function mutations in cystic fibrosis transmembrane conductance regulator
- Unmuted copy is sufficient for functioning
- Most common genetic disease that affects Caucasian populations
- Affects fluid secretions: thickened mucous, pulmonary infections, pancreatic function, bile duct blockage, affects sweat glands
X-linked recessive
circle with blue dot= carrier female
daughters are unaffected
affected males pass mutant gene to all daughters
do not pass trait to sons
usually only males are affected
Examples: Hemophilia A and B, G6PD deficiency
Karyotype analysis
collect blood cells and halt subdivision in metaphase and they isolate the chromosomes from the cells and stain them (G banding) this is how you diagnose a genetic disease
Down syndrome
Trisomy 21: 3 copies instead of 2
- Excessive skin on back of neck
- Transverse palmer crease
- Folded or dysplastic ear
- Mental retardation
