CBCL1: Medical Genetics Chapters 5, 6, 7 Flashcards
Missense Mutation
single base change resulting in a change in Amino Acid
Nonsense Mutation
Changes base pair to stop codon
->results in premature trunkation of protein, deleterious
Frameshift Mutation
insertion or deletion of bases in anything other than multiple of 3
->results in stop codon creation within several codons or unstable protein, deleterious
3’ end of Exon ends in:
AG
*Note: Mutation here technically can be “silent” because it doesn’t result in a change in AA, but still can have a phenotypic effect because of an alteration in splicing
5’ end of an Intron adjacent to an exon is:
3’ end of an Intron:
GT (splice donor)
AG (splice acceptor)
Loss of Function Mutation:
Reduced Amount or Reduced activity of a gene product.
->minimum effect unless homozygous for alleles
Recessive Phenotype
Homozygous for a Loss of Function alleles
Null Allele
Loss of function allele when Heterozygous for this mutation (the shitty allele)
Haploinsufficiency
Heterozygous for Loss of Function alleles, but decrease in levels of gene product results in altered phenotype from mutation in null allele.
–>This altered phenotype is considered a Dominant Phenotype
Dominant Phenotype
Phenotype produced when heterozygous for a gene.
–>NOTE*: can be phenotype produced by haploinsufficiency
Dosage Sensitivity
a change in phenotype produced from gene A because of insufficient interaction with product of gene b. Insufficient interaction results because of low concentration of product of gene B as a result of haploinsuffiency.
Dominant Negative Effect
Heterozygous for Loss of Function mutation and product of mutant allele interferes with product of normal allele
–>typically more severe than loss of product
Gain of Function Mutation
Produce an Increased amount or Increased activity of a gene product
- ->Very specific changes allowing for formation of a product with enhanced activity of its existing function or new function
- ->Often missense in specific location OR frameshift expansion in microsatellite repeat areas (CAG triplet expansion = Huntington’s)
First Degree Relatives
Parents, Siblings, and children
Second Degree Relatives
Grandma/Grandpa, Aunts/Uncles, Nephews/Nieces, half-siblings
Third Degree Relatives
First Cousins, Great Grandparents
Consanguinity
Blood relationship between descendants of a common ancestor (inbreeding)
Autosomal Dominant Inheritance Pattern:
- Males and Females equally affected
- Males and Females equally capable of transmitting trait
- Affected person usually has one affected parent
- 50% probability of transmitting the trait
(commonly non-enzymatic protein)`
Autosomal Recessive Inheritance
- Both parents usually asymptomatic carriers
- M and F equally affected
- Increased with Inbreeding
- Unaffected parents with 1 affected child have 25% chance of having another affected child with each pregnancy
- unaffected siblings have 2/3 risk of being a carrier
X-Linked Recessive
- Affects Males
- All daughters of affected males are carriers
- Females are affected if they have an affected father and carrier mother
- Female carriers have 50% risk of passing it on to son or 50% of having carrier daugher
X-Linked Dominant
- Both Males and Females may be affected
- Females usually less evident
- pedigree looks similar to autosomal dominant BUT NO MALE TO MALE TRANSMISSION
Mosaicism is caused by:
de novo mutations in parental gamete
–>Often looks like autosomal recessive pedigree
Clinical heterogeneity
mutations in same gene produce different clinical disorder
Allelic heterogeneity
multiple mutations within the same allele cause the same disorder
Locus heterogeneity
mutations at more than one gene locus cause same disease (differs from clinical hetrogeneity cuz on different genes not different mutations in SAME gene)
heteroplasmy
mixed normal and abnormal mitochondrial genomes within each cell
haplotype
a set of polymorphisms in different genes that reside closely on a given chromosome and are often inherited together. A particular haplotype can correlate with disease severity.
